Identification

Name
Nortriptyline
Accession Number
DB00540
Description

Nortriptyline hydrochloride, the active metabolite of amitriptyline, is a tricyclic antidepressant (TCA).16 It is used in the treatment of major depression and is also used off-label for chronic pain and other conditions.17

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 263.3767
Monoisotopic: 263.167399677
Chemical Formula
C19H21N
Synonyms
  • 10,11-dihydro-N-methyl-5H-dibenzo[a,d]cycloheptene-Δ5,γ-propylamine
  • 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine
  • Demethylamitriptyline
  • Desmethylamitriptyline
  • Nortriptylina
  • Nortriptyline
  • Nortriptylinum
External IDs
  • NCI-169453

Pharmacology

Indication

Nortriptyline is indicated for the relief of the symptoms of major depressive disorder (MDD).16 Some off-label uses for this drug include treatment of chronic pain, myofascial pain, neuralgia, and irritable bowel syndrome.7,16

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
Pharmacodynamics

Nortriptyline exerts antidepressant effects likely by inhibiting the reuptake of serotonin and norepinephrine at neuronal cell membranes. It also exerts antimuscarinic effects through its actions on the acetylcholine receptor.16,17

Mechanism of action

Though prescribing information does not identify a specific mechanism of action for nortriptyline16, is believed that nortriptyline either inhibits the reuptake of the neurotransmitter serotonin at the neuronal membrane or acts at the level of the beta-adrenergic receptors. It displays a more selective reuptake inhibition for noradrenaline, which may explain increased symptom improvement after nortriptyline therapy.14 Tricyclic antidepressants do not inhibit monoamine oxidase nor do they affect dopamine reuptake.16 As with other tricyclics, nortriptyline displays affinity for other receptors including mACh receptors, histamine receptors, 5-HT receptors, in addition to other receptors.10,11,14

TargetActionsOrganism
ASodium-dependent noradrenaline transporter
inhibitor
Humans
ASodium-dependent serotonin transporter
inhibitor
Humans
A5-hydroxytryptamine receptor 2A
antagonist
Humans
U5-hydroxytryptamine receptor 1A
antagonist
Humans
NHistamine H1 receptor
antagonist
Humans
NAlpha-1A adrenergic receptor
antagonist
Humans
NAlpha-1D adrenergic receptor
antagonist
Humans
U5-hydroxytryptamine receptor 2C
antagonist
downregulator
Humans
UAlpha-1B adrenergic receptor
antagonist
Humans
UAlpha-2 adrenergic receptors
antagonist
Humans
UBeta adrenergic receptor
antagonist
Humans
UDopamine D2 receptor
antagonist
Humans
USigma receptor
binder
Humans
U5-hydroxytryptamine receptor 1C
antagonist
Rat
UMuscarinic acetylcholine receptor
antagonist
Humans
Absorption

Nortriptyline is readily absorbed in the gastrointestinal tract with extensive variation in plasma levels, depending on the patient. This drug undergoes first-pass metabolism and its plasma concentrations are attained within 7 to 8.5 hours after oral administration.18 The bioavailability of nortriptyline varies considerably and ranges from 45 to 85%.12,19

Volume of distribution

The apparent volume of distribution (Vd)β, estimated after intravenous administration is 1633 ± 268 L within the range of 1460 to 2030 (21 ± 4 L/kg).19 Nortriptyline crosses the placenta and is found in the breast milk. It distributes to the heart, lungs, brain, and the liver.18

Protein binding

The plasma protein binding of nortriptyline is approximately 93%.19

Metabolism

Nortriptyline is metabolized via demethylation and hydroxylation in the liver followed by glucuronic acid conjugation. CYP2D6 plays a large role in nortriptyline metabolism, with contributions from CYP1A2, CYP2C19 and CY3A4.16,18 The main active metabolite is 10-hydroxynortriptyline exists in both cis and a trans form, with the trans form is higher in potency. 10-hydroxynortriptyline is the most frequently found in the plasma. Most of the other metabolites are conjugated, and are less potent.19

Hover over products below to view reaction partners

Route of elimination

Nortriptyline and its metabolites are mainly excreted in the urine, where only small amounts (2%) of the total drug is recovered as unchanged parent compound.19 Approximately one-third of a single orally administered dose is excreted in urine within 24 hours.18 Small amounts are excreted in feces via biliary elimination.19

Half-life

The average plasma half-life of nortriptyline in healthy volunteers is about 26 hours, but is said to range from 16 to 38 hours.8,16,19 One study mentions a mean half-life of about 39 hours.9

Clearance

The average plasma clearance of nortriptyline in a study of healthy volunteers was 54 L/h.8 The average systemic clearance of nortriptyline is 30.6 ± 6.9 L / h, within the range of 18.6 to 39.6 L/hour.19

Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
Toxicity

The oral LD50 of nortriptyline in the rat is 405 mg/kg.20Symptoms of overdose with nortriptyline include cardiac arrhythmias, severe hypotension, shock, congestive heart failure, pulmonary edema, convulsions, coma, and CNS depression.16,18 Changes in the electrocardiogram, particularly in QRS segment, may be indicative of tricyclic antidepressant toxicity.13

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*3Not Available2549delAEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableA alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer. For individual with two non-functional alleles, alternative drug or dose reduction recommended.Details
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, higher risk for adverse side effectsDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableG alleleEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details
Cytochrome P450 2D6CYP2D6*4Not Available3877G>AEffect Directly StudiedThe presence of this polymorphism in CYP2D6 is associated with reduced or poor metabolism of nortriptyline.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Nortriptyline can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Nortriptyline can be increased when combined with Abatacept.
AbirateroneThe serum concentration of Nortriptyline can be increased when it is combined with Abiraterone.
AcalabrutinibThe metabolism of Nortriptyline can be decreased when combined with Acalabrutinib.
AcarboseNortriptyline may decrease the hypoglycemic activities of Acarbose.
AcebutololNortriptyline may increase the orthostatic hypotensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Nortriptyline is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Nortriptyline is combined with Acemetacin.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Nortriptyline.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Nortriptyline.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
  • Avoid alcohol.
  • Take with or without food. Food decreases gastrointestinal irritation.

Products

Product Ingredients
IngredientUNIICASInChI Key
Nortriptyline hydrochloride00FN6IH15D894-71-3SHAYBENGXDALFF-UHFFFAOYSA-N
Product Images
International/Other Brands
Allegron / Ateben / Avantyl / Noritren / Norpress / Nortrilen / Psychostyl / Sensaval / Sensoval
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AventylCapsuleOralAa Pharma Inc1965-12-31Not applicableCanada flag
AventylCapsuleOralAa Pharma Inc1965-12-31Not applicableCanada flag
NortriptylineCapsuleOralPharmel Inc1998-06-042014-09-08Canada flag
NortriptylineCapsuleOralPharmel Inc1998-06-042014-09-08Canada flag
Nortriptyline HydrochlorideSolution10 mg/5mLOralRanbaxy Inc.2008-01-04Not applicableUS flag
Nortriptyline HydrochlorideSolution10 mg/5mLOralTaro Pharmaceuticals U.S.A., Inc.2008-11-04Not applicableUS flag
Nortriptyline-10CapsuleOralPro Doc Limitee2008-03-072016-07-18Canada flag
Nortriptyline-25CapsuleOralPro Doc Limitee2008-03-072016-07-18Canada flag
NorventylCapsuleOralValeant Canada Lp Valeant Canada S.E.C.1997-02-042014-07-30Canada flag
NorventylCapsuleOralValeant Canada Lp Valeant Canada S.E.C.1997-02-042014-07-30Canada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-nortriptyline - Cap 10mgCapsuleOralApotex Corporation1996-09-26Not applicableCanada flag
Apo-nortriptyline - Cap 25mgCapsuleOralApotex Corporation1996-09-26Not applicableCanada flag
Ava-nortriptylineCapsuleOralAvanstra Inc2011-11-282014-08-21Canada flag
Ava-nortriptylineCapsuleOralAvanstra Inc2011-11-282014-08-21Canada flag
Dom-nortriptyline 10mg CapsulesCapsuleOralDominion Pharmacal1995-10-012014-09-08Canada flag
Dom-nortriptyline 25mg CapsulesCapsuleOralDominion Pharmacal1995-10-012014-09-08Canada flag
Gen-nortriptyline Capsules 10mgCapsuleOralGenpharm Ulc1997-09-052009-08-05Canada flag
Gen-nortriptyline Capsules 25mgCapsuleOralGenpharm Ulc1997-09-052009-08-05Canada flag
Nortriptyline HciCapsule25 mg/1OralDirect_Rx2019-08-22Not applicableUS flag
Nortriptyline HCLCapsule10 mg/1OralDirect_Rx2019-06-04Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more

Categories

ATC Codes
N06AA10 — Nortriptyline
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dibenzocycloheptenes. These are compounds containing a dibenzocycloheptene moiety, which consists of two benzene rings connected by a cycloheptene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Dibenzocycloheptenes
Sub Class
Not Available
Direct Parent
Dibenzocycloheptenes
Alternative Parents
Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Amine / Aromatic homopolycyclic compound / Dibenzocycloheptene / Hydrocarbon derivative / Organic nitrogen compound / Organonitrogen compound / Organopnictogen compound / Secondary aliphatic amine / Secondary amine
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
organic tricyclic compound (CHEBI:7640)

Chemical Identifiers

UNII
BL03SY4LXB
CAS number
72-69-5
InChI Key
PHVGLTMQBUFIQQ-UHFFFAOYSA-N
InChI
InChI=1S/C19H21N/c1-20-14-6-11-19-17-9-4-2-7-15(17)12-13-16-8-3-5-10-18(16)19/h2-5,7-11,20H,6,12-14H2,1H3
IUPAC Name
methyl(3-{tricyclo[9.4.0.0³,⁸]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
SMILES
CNCCC=C1C2=CC=CC=C2CCC2=CC=CC=C12

References

Synthesis Reference

Abraham Nudelman, "ACID ADDITION SALT OF A NORTRIPTYLINE-GABA CONJUGATE AND A PROCESS OF PREPARING SAME." U.S. Patent US20130184347, issued July 18, 2013.

US20130184347
General References
  1. Prochazka AV, Weaver MJ, Keller RT, Fryer GE, Licari PA, Lofaso D: A randomized trial of nortriptyline for smoking cessation. Arch Intern Med. 1998 Oct 12;158(18):2035-9. [PubMed:9778204]
  2. Nelson JC, Kennedy JS, Pollock BG, Laghrissi-Thode F, Narayan M, Nobler MS, Robin DW, Gergel I, McCafferty J, Roose S: Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease. Am J Psychiatry. 1999 Jul;156(7):1024-8. doi: 10.1176/ajp.156.7.1024. [PubMed:10401446]
  3. Fabre LF, Scharf MB, Itil TM: Comparative efficacy and safety of nortriptyline and fluoxetine in the treatment of major depression: a clinical study. J Clin Psychiatry. 1991 Jun;52 Suppl:62-7. [PubMed:2050651]
  4. Heymann RE, Helfenstein M, Feldman D: A double-blind, randomized, controlled study of amitriptyline, nortriptyline and placebo in patients with fibromyalgia. An analysis of outcome measures. Clin Exp Rheumatol. 2001 Nov-Dec;19(6):697-702. [PubMed:11791642]
  5. Lustman PJ, Griffith LS, Clouse RE, Freedland KE, Eisen SA, Rubin EH, Carney RM, McGill JB: Effects of nortriptyline on depression and glycemic control in diabetes: results of a double-blind, placebo-controlled trial. Psychosom Med. 1997 May-Jun;59(3):241-50. [PubMed:9178335]
  6. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. [PubMed:17471183]
  7. Clouse RE: Antidepressants for irritable bowel syndrome. Gut. 2003 Apr;52(4):598-9. doi: 10.1136/gut.52.4.598. [PubMed:12631677]
  8. Dawling S, Crome P, Braithwaite R: Pharmacokinetics of single oral doses of nortriptyline in depressed elderly hospital patients and young healthy volunteers. Clin Pharmacokinet. 1980 Jul-Aug;5(4):394-401. doi: 10.2165/00003088-198005040-00007. [PubMed:6994983]
  9. Overo KF: Pharmacokinetic aspects on once-daily nortriptyline administration. Neuropsychobiology. 1980;6(1):34-41. doi: 10.1159/000117730. [PubMed:7366812]
  10. Peroutka SJ, Snyder SH: Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet. 1982 Mar 20;1(8273):658-9. [PubMed:6121969]
  11. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  12. Gibaldi M: Comparison of observed and predicted bioavailability of nortriptyline in humans following oral administration. J Pharm Sci. 1975 Jun;64(6):1036-7. doi: 10.1002/jps.2600640635. [PubMed:1133723]
  13. Elsamadisi P, Sclafani A, Eche IM: Delayed Cardiotoxicity From a Massive Nortriptyline Overdose Requiring Prolonged Treatment. J Pharm Pract. 2019 Apr 14:897190019838700. doi: 10.1177/0897190019838700. [PubMed:30983469]
  14. 46. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 574-575). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  15. EMC Summary of product characteristics: Nortriptyline [Link]
  16. FDA Approved Products: Nortriptyline oral capsules and oral solution [Link]
  17. NIH StatPearls: Nortriptyline [Link]
  18. Product monograph: Nortriptyline tablets [Link]
  19. MedSafe NZ data sheet: Nortriptyline tablets [Link]
  20. CaymanChem MSDS: Nortriptyline [Link]
Human Metabolome Database
HMDB0014680
KEGG Drug
D08288
KEGG Compound
C07274
PubChem Compound
4543
PubChem Substance
46507783
ChemSpider
4384
BindingDB
112777
RxNav
7531
ChEBI
7640
ChEMBL
CHEMBL445
ZINC
ZINC000001530741
Therapeutic Targets Database
DAP001152
PharmGKB
PA450657
Guide to Pharmacology
GtP Drug Page
PDBe Ligand
21B
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Nortriptyline
AHFS Codes
  • 28:16.04.28 — Tricyclics and Other Norepinephrine-reuptake Inhibitors
PDB Entries
4m48
FDA label
Download (376 KB)
MSDS
Download (38.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentGeriatric Depression / Late Life Depression (LLD) / Major Depressive Disorder (MDD) / Major depressive disorder, recurrent episode / Treatment Resistant Depression (TRD) / Treatment-Refractory Depression1
4CompletedTreatmentBipolar Disorder (BD)1
4CompletedTreatmentBipolar Disorder (BD) / Depression / Depressive Disorders1
4CompletedTreatmentCryptogenic Sensory Polyneuropathy1
4CompletedTreatmentDepression2
4CompletedTreatmentDepression / Melancholic Depression1
4CompletedTreatmentGastro-esophageal Reflux Disease (GERD)1
4CompletedTreatmentMajor Depressive Disorder (MDD)1
4Enrolling by InvitationTreatmentConcussion Post Syndrome / Headaches Posttraumatic / Mild Traumatic Brain Injury (MTBI)1
4TerminatedPreventionDepression1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Tyco healthcare group lp
  • Ranbaxy pharmaceuticals inc
  • Pharmaceutical assoc inc
  • Taro pharmaceutical industries ltd
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Caremark LLC
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Gallipot
  • H.J. Harkins Co. Inc.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Keltman Pharmaceuticals Inc.
  • Lake Erie Medical and Surgical Supply
  • Major Pharmaceuticals
  • Mallinckrodt Inc.
  • Mckesson Corp.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • Patheon Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Association
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Prescription Dispensing Service Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Southwood Pharmaceuticals
  • St Mary's Medical Park Pharmacy
  • Stat Rx Usa
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • UDL Laboratories
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
Dosage Forms
FormRouteStrength
CapsuleOral
Tablet, coatedOral500 mg
Tablet, coatedOral10 MG
Tablet, coatedOral25 MG
Tablet, film coatedOral10 MG
Tablet, film coatedOral25 MG
CapsuleOral10 mg/1
CapsuleOral25 mg/1
CapsuleOral50 mg/1
CapsuleOral75 mg/1
SolutionOral10 mg/5mL
SolutionOral20 mg/10mL
SolutionOral2 mg/1mL
Prices
Unit descriptionCostUnit
Pamelor 30 10 mg capsule Bottle750.05USD bottle
Pamelor 30 25 mg capsule Bottle750.05USD bottle
Pamelor 30 50 mg capsule Bottle750.05USD bottle
Pamelor 10 mg/5ml Solution 480ml Bottle325.97USD bottle
Pamelor 10 mg capsule24.04USD capsule
Pamelor 25 mg capsule24.04USD capsule
Pamelor 50 mg capsule24.04USD capsule
Pamelor 75 mg capsule19.34USD capsule
Nortriptyline hcl powder11.09USD g
Nortriptyline hcl 75 mg capsule1.33USD capsule
Nortriptyline hcl 50 mg capsule0.94USD capsule
Nortriptyline hcl 25 mg capsule0.6USD capsule
Aventyl 25 mg Capsule0.48USD capsule
Nortriptyline HCl 10 mg/5ml Solution0.4USD ml
Nortriptyline hcl 10 mg capsule0.28USD capsule
Apo-Nortriptyline 25 mg Capsule0.27USD capsule
Novo-Nortriptyline 25 mg Capsule0.27USD capsule
Nu-Nortriptyline 25 mg Capsule0.27USD capsule
Pms-Nortriptyline 25 mg Capsule0.27USD capsule
Aventyl 10 mg Capsule0.24USD capsule
Apo-Nortriptyline 10 mg Capsule0.13USD capsule
Novo-Nortriptyline 10 mg Capsule0.13USD capsule
Nu-Nortriptyline 10 mg Capsule0.13USD capsule
Pms-Nortriptyline 10 mg Capsule0.13USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)58https://www.chemicalbook.com/ChemicalProductProperty_US_CB1317147.aspx
boiling point (°C)396.62https://www.chemicalbook.com/ChemicalProductProperty_US_CB1317147.aspx
water solubility0.00087 g/Lhttp://www.hmdb.ca/metabolites/HMDB0014680
logP3.9Lead Optimization for Medicinal Chemists (2012)
logS-5.5http://www.hmdb.ca/metabolites/HMDB0014680
pKa9.7https://www.chemicalbook.com/ChemicalProductProperty_US_CB1317147.aspx
Predicted Properties
PropertyValueSource
Water Solubility0.000874 mg/mLALOGPS
logP4.65ALOGPS
logP4.43ChemAxon
logS-5.5ALOGPS
pKa (Strongest Basic)10.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity96.21 m3·mol-1ChemAxon
Polarizability31.87 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9478
Caco-2 permeable+0.774
P-glycoprotein substrateSubstrate0.7863
P-glycoprotein inhibitor IInhibitor0.8876
P-glycoprotein inhibitor IIInhibitor0.5376
Renal organic cation transporterInhibitor0.6903
CYP450 2C9 substrateNon-substrate0.7508
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.5593
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.7665
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5194
Ames testNon AMES toxic0.5315
CarcinogenicityNon-carcinogens0.9182
BiodegradationReady biodegradable0.5
Rat acute toxicity2.7513 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5809
hERG inhibition (predictor II)Inhibitor0.7763
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (7.76 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - EI-BGC-MSsplash10-0006-9000000000-bb9eae4818c0402317ee
Mass Spectrum (Electron Ionization)MSsplash10-0006-9230000000-15f73e5232a0e230f41b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-05nf-5970000000-f92c7d23474b57a4ba50
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-03di-0090000000-4c40cb3ec4df8809981e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-06sl-2590000000-be2abd28b2b0f75dd8bb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05mo-3940000000-6a454924ec75665c6175
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-05mo-3930000000-eb8141866b19782dd1e5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-4930000000-81614e655fc32d5839ce
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00kf-4930000000-f918306a99d07f887503
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gdl-5930000000-d876ab376d0e9885d06d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gb9-5930000000-e51a246750bf8ce7e4ec
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0gbi-5930000000-c2811578219a3a7e1ccf
MS/MS Spectrum - , positiveLC-MS/MSsplash10-03yi-0490000000-094e7bdb831aed030f5f

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Roubert C, Cox PJ, Bruss M, Hamon M, Bonisch H, Giros B: Determination of residues in the norepinephrine transporter that are critical for tricyclic antidepressant affinity. J Biol Chem. 2001 Mar 16;276(11):8254-60. Epub 2000 Nov 22. [PubMed:11092898]
  2. Roubert C, Sagne C, Kapsimali M, Vernier P, Bourrat F, Giros B: A Na(+)/Cl(-)-dependent transporter for catecholamines, identified as a norepinephrine transporter, is expressed in the brain of the teleost fish medaka (Oryzias latipes). Mol Pharmacol. 2001 Sep;60(3):462-73. [PubMed:11502876]
  3. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed:14744476]
  4. Kim H, Lim SW, Kim S, Kim JW, Chang YH, Carroll BJ, Kim DK: Monoamine transporter gene polymorphisms and antidepressant response in koreans with late-life depression. JAMA. 2006 Oct 4;296(13):1609-18. [PubMed:17018806]
  5. Barker EL, Blakely RD: Identification of a single amino acid, phenylalanine 586, that is responsible for high affinity interactions of tricyclic antidepressants with the human serotonin transporter. Mol Pharmacol. 1996 Oct;50(4):957-65. [PubMed:8863842]
  6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  7. NIH StatPearls: Nortriptyline [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Joyce PR, Mulder RT, Luty SE, McKenzie JM, Miller AL, Rogers GR, Kennedy MA: Age-dependent antidepressant pharmacogenomics: polymorphisms of the serotonin transporter and G protein beta3 subunit as predictors of response to fluoxetine and nortriptyline. Int J Neuropsychopharmacol. 2003 Dec;6(4):339-46. [PubMed:14604448]
  2. Wisner KL, Hanusa BH, Perel JM, Peindl KS, Piontek CM, Sit DK, Findling RL, Moses-Kolko EL: Postpartum depression: a randomized trial of sertraline versus nortriptyline. J Clin Psychopharmacol. 2006 Aug;26(4):353-60. [PubMed:16855451]
  3. Pollock BG, Ferrell RE, Mulsant BH, Mazumdar S, Miller M, Sweet RA, Davis S, Kirshner MA, Houck PR, Stack JA, Reynolds CF, Kupfer DJ: Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology. 2000 Nov;23(5):587-90. [PubMed:11027924]
  4. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed:14744476]
  5. Rausch JL, Moeller FG, Johnson ME: Initial platelet serotonin (5-HT) transport kinetics predict nortriptyline treatment outcome. J Clin Psychopharmacol. 2003 Apr;23(2):138-44. [PubMed:12640215]
  6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [PubMed:9537821]
  7. NIH StatPearls: Nortriptyline [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Sanchez C, Hyttel J: Comparison of the effects of antidepressants and their metabolites on reuptake of biogenic amines and on receptor binding. Cell Mol Neurobiol. 1999 Aug;19(4):467-89. [PubMed:10379421]
  3. Bravo L, Llorca-Torralba M, Berrocoso E, Mico JA: Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain. Front Neurosci. 2019 Nov 26;13:1268. doi: 10.3389/fnins.2019.01268. eCollection 2019. [PubMed:31942167]
  4. NIH StatPearls: Nortriptyline [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Shrestha SS, Pine DS, Luckenbaugh DA, Varnas K, Henter ID, Innis RB, Mathe AA, Svenningsson P: Antidepressant effects on serotonin 1A/1B receptors in the rat brain using a gene x environment model. Neurosci Lett. 2014 Jan 24;559:163-8. doi: 10.1016/j.neulet.2013.11.034. Epub 2013 Nov 25. [PubMed:24287374]
  3. Bravo L, Llorca-Torralba M, Berrocoso E, Mico JA: Monoamines as Drug Targets in Chronic Pain: Focusing on Neuropathic Pain. Front Neurosci. 2019 Nov 26;13:1268. doi: 10.3389/fnins.2019.01268. eCollection 2019. [PubMed:31942167]
Details
5. Histamine H1 receptor
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
General Function
Histamine receptor activity
Specific Function
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamin...
Gene Name
HRH1
Uniprot ID
P35367
Uniprot Name
Histamine H1 receptor
Molecular Weight
55783.61 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Sadava D, Wilmington K: Tricyclic antidepressant drugs affect histamine receptors in human leukocytes. Life Sci. 1984 Dec 17;35(25):2545-8. [PubMed:6096660]
  3. Taylor JE, Richelson E: High affinity binding of tricyclic antidepressants to histamine H1-receptors: fact and artifact. Eur J Pharmacol. 1980 Oct 3;67(1):41-6. [PubMed:6106553]
  4. NIH StatPearls: Nortriptyline [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1A
Uniprot ID
P35348
Uniprot Name
Alpha-1A adrenergic receptor
Molecular Weight
51486.005 Da
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]
  2. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
  3. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [PubMed:2870173]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Antagonist
General Function
Alpha1-adrenergic receptor activity
Specific Function
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Gene Name
ADRA1D
Uniprot ID
P25100
Uniprot Name
Alpha-1D adrenergic receptor
Molecular Weight
60462.205 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
Downregulator
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Palvimaki EP, Roth BL, Majasuo H, Laakso A, Kuoppamaki M, Syvalahti E, Hietala J: Interactions of selective serotonin reuptake inhibitors with the serotonin 5-HT2c receptor. Psychopharmacology (Berl). 1996 Aug;126(3):234-40. [PubMed:8876023]
  2. Stahl SM, Hauger RL, Rausch JL, Fleishaker JC, Hubbell-Alberts E: Downregulation of serotonin receptor subtypes by nortriptyline and adinazolam in major depressive disorder: neuroendocrine and platelet markers. Clin Neuropharmacol. 1993;16 Suppl 3:S19-31. [PubMed:8131152]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Protein heterodimerization activity
Specific Function
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) prot...
Gene Name
ADRA1B
Uniprot ID
P35368
Uniprot Name
Alpha-1B adrenergic receptor
Molecular Weight
56835.375 Da
References
  1. Nojimoto FD, Mueller A, Hebeler-Barbosa F, Akinaga J, Lima V, Kiguti LR, Pupo AS: The tricyclic antidepressants amitriptyline, nortriptyline and imipramine are weak antagonists of human and rat alpha1B-adrenoceptors. Neuropharmacology. 2010 Jul-Aug;59(1-2):49-57. doi: 10.1016/j.neuropharm.2010.03.015. Epub 2010 Apr 2. [PubMed:20363235]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Thioesterase binding
Specific Function
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazo...

Components:
References
  1. Zebrowska-Lupina I, Kozyrska C, Stelmasiak M: Interaction between antidepressants and alpha-adrenergic receptor blocking agents. Pol J Pharmacol Pharm. 1980 Sep-Oct;32(5):673-80. [PubMed:6115370]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
  3. PDSP Ki Database [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Receptor signaling protein activity
Specific Function
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately e...

Components:
References
  1. Yalcin I, Choucair-Jaafar N, Benbouzid M, Tessier LH, Muller A, Hein L, Freund-Mercier MJ, Barrot M: beta(2)-adrenoceptors are critical for antidepressant treatment of neuropathic pain. Ann Neurol. 2009 Feb;65(2):218-25. doi: 10.1002/ana.21542. [PubMed:19259968]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
  3. PDSP Ki Database [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Potassium channel regulator activity
Specific Function
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name
DRD2
Uniprot ID
P14416
Uniprot Name
D(2) dopamine receptor
Molecular Weight
50618.91 Da
References
  1. Peroutka SJ, Snyder SH: Antiemetics: neurotransmitter receptor binding predicts therapeutic actions. Lancet. 1982 Mar 20;1(8273):658-9. [PubMed:6121969]
  2. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
  3. PDSP Ki Database [Link]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Binder
General Function
Steroid binding
Specific Function
Receptor for progesterone.

Components:
References
  1. Goodman, Louis Sanford;Brunton, Laurence L.;Chabner, Bruce;Knollman, Bjorn (2011). The Pharmacological Basis of Therapeutics (12th ed.). McGraw-Hill Professional Publishing. [ISBN:978-0-07-162442-8]
  2. PDSP Ki Database [Link]
Kind
Protein
Organism
Rat
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
Htr2c
Uniprot ID
P08909
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51916.005 Da
References
  1. Jenck F, Moreau JL, Mutel V, Martin JR, Haefely WE: Evidence for a role of 5-HT1C receptors in the antiserotonergic properties of some antidepressant drugs. Eur J Pharmacol. 1993 Feb 9;231(2):223-9. doi: 10.1016/0014-2999(93)90453-o. [PubMed:8453978]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...

Components:
References
  1. Cusack B, Nelson A, Richelson E: Binding of antidepressants to human brain receptors: focus on newer generation compounds. Psychopharmacology (Berl). 1994 May;114(4):559-65. [PubMed:7855217]

Enzymes

Details
1. Cytochrome P450 2D6
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  3. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol. 1999 Jun;39(6):567-77. [PubMed:10354960]
  4. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. [PubMed:9193876]
  5. Ryu S, Park S, Lee JH, Kim YR, Na HS, Lim HS, Choi HY, Hwang IY, Lee JG, Park ZW, Oh WY, Kim JM, Choi SE: A Study on CYP2C19 and CYP2D6 Polymorphic Effects on Pharmacokinetics and Pharmacodynamics of Amitriptyline in Healthy Koreans. Clin Transl Sci. 2017 Mar;10(2):93-101. doi: 10.1111/cts.12451. Epub 2017 Mar 14. [PubMed:28296334]
  6. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Venkatakrishnan K, von Moltke LL, Greenblatt DJ: Nortriptyline E-10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3A4 (low affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol. 1999 Jun;39(6):567-77. [PubMed:10354960]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
  2. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. [PubMed:9193876]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Olesen OV, Linnet K: Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos. 1997 Jun;25(6):740-4. [PubMed:9193876]
  2. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Wen B, Ma L, Zhu M: Bioactivation of the tricyclic antidepressant amitriptyline and its metabolite nortriptyline to arene oxide intermediates in human liver microsomes and recombinant P450s. Chem Biol Interact. 2008 May 9;173(1):59-67. doi: 10.1016/j.cbi.2008.02.001. Epub 2008 Feb 14. [PubMed:18359012]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Information regarding this enzyme action in the literature is limited to one in vitro study. Clinical correlation is unknown.
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Tassaneeyakul W, Birkett DJ, Miners JO: Inhibition of human hepatic cytochrome P4502E1 by azole antifungals, CNS-active drugs and non-steroidal anti-inflammatory agents. Xenobiotica. 1998 Mar;28(3):293-301. doi: 10.1080/004982598239579 . [PubMed:9574817]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. doi: 10.1007/bf00498432. [PubMed:6108517]
  2. Pike E, Skuterud B: Plasma binding variations of amitriptyline and nortriptyline. Clin Pharmacol Ther. 1982 Aug;32(2):228-34. doi: 10.1038/clpt.1982.152. [PubMed:7094510]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da
References
  1. Brinkschulte M, Breyer-Pfaff U: The contribution of alpha 1-acid glycoprotein, lipoproteins, and albumin to the plasma binding of perazine, amitriptyline, and nortriptyline in healthy man. Naunyn Schmiedebergs Arch Pharmacol. 1980 Oct;314(1):61-6. doi: 10.1007/bf00498432. [PubMed:6108517]
  2. Ferry DG, Caplan NB, Cubeddu LX: Interaction between antidepressants and alpha 1-adrenergic receptor antagonists on the binding to alpha 1-acid glycoprotein. J Pharm Sci. 1986 Feb;75(2):146-9. doi: 10.1002/jps.2600750208. [PubMed:2870173]
  3. Pike E, Skuterud B: Plasma binding variations of amitriptyline and nortriptyline. Clin Pharmacol Ther. 1982 Aug;32(2):228-34. doi: 10.1038/clpt.1982.152. [PubMed:7094510]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Takano H, Arakawa R, Nogami T, Suzuki M, Nagashima T, Fujiwara H, Kimura Y, Kodaka F, Takahata K, Shimada H, Murakami Y, Tateno A, Yamada M, Ito H, Kawamura K, Zhang MR, Takahashi H, Kato M, Okubo Y, Suhara T: Norepinephrine transporter occupancy by nortriptyline in patients with depression: a positron emission tomography study with (S,S)-[(1)(8)F]FMeNER-D(2). Int J Neuropsychopharmacol. 2014 Apr;17(4):553-60. doi: 10.1017/S1461145713001521. Epub 2013 Dec 18. [PubMed:24345533]
  2. Zhou J: Norepinephrine transporter inhibitors and their therapeutic potential. Drugs Future. 2004 Dec;29(12):1235-1244. [PubMed:16871320]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Roberts RL, Joyce PR, Mulder RT, Begg EJ, Kennedy MA: A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression. Pharmacogenomics J. 2002;2(3):191-6. [PubMed:12082591]
  2. Ejsing TB, Linnet K: Influence of P-glycoprotein inhibition on the distribution of the tricyclic antidepressant nortriptyline over the blood-brain barrier. Hum Psychopharmacol. 2005 Mar;20(2):149-53. doi: 10.1002/hup.667. [PubMed:15624117]

Drug created on June 13, 2005 07:24 / Updated on September 17, 2020 23:28

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates