Lorpiprazole

Identification

Generic Name

Lorpiprazole

DrugBank Accession Number

DB09195

Background

Lorpiprazole is a serotonin antagonist and reuptake inhibitor used for the treatment of major depressive disorder.¹ It is a piperazinyl-triazole derivative.³

Type

Small Molecule

Groups

Approved

Structure

Similar Structures

Weight: Average: 405.469
Monoisotopic: 405.214030346
Chemical Formula: C₂₁H₂₆F₃N₅

Synonyms

Lorpiprazole

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Pharmacology

Indication

In 2016, lorpiprazole was classified in the "Chemical structure-related drug-like criteria of global approved drugs" as an antipsychotic and anxiolytic.⁶ An antipsychotic is a medication used to treat a state of delusion, hallucination, paranoia or disordered thought. On the other hand, an anxiolytic is a medication used for the treatment of severe, chronic or debilitating anxiety. The anxiety state can be defined as an unpleasant state of tension, apprehension or uneasiness.⁴

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Contraindications & Blackbox Warnings

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Pharmacodynamics

Drugs like lorpiprazole that fit in the category of serotonin antagonists and reuptake inhibitors present a wide variety of effects when administered. They inhibit serotonin receptors like 5-HT2A as well as prevent the reuptake of serotonin, norepinephrine and dopamine. Additionally, they antagonize some adrenergic receptors. This diverse functional profile allows lorpiprazole to have a large therapeutic spectrum from symptom control as an adjuvant of other drugs to control of depressive syndromes as a monotherapy.²

Mechanism of action

Lorpiprazole is a serotonin antagonist and reuptake inhibitor thus, its activity is performed by antagonizing the 5-HT2A and the 5-HT2C serotoninergic receptors as well as the alpha1 and alpha2 adrenergic receptors, H1 histaminergic receptors and at high doses, inhibiting the SERT serotonin transporter.²

Target	Actions	Organism
A5-hydroxytryptamine receptor 2A	antagonist	Humans
A5-hydroxytryptamine receptor 2C	antagonist	Humans
AAlpha-1 adrenergic receptors	antagonist	Humans
AAlpha-2 adrenergic receptors	antagonist	Humans
AHistamine H1 receptor	antagonist	Humans
ASodium-dependent serotonin transporter	antagonist	Humans

Absorption

After oral administration, the serotonin antagonist and reuptake inhibitors are rapidly absorbed in the gastrointestinal tract. This absorption can be slow down depending on the type of diet. The maximum plasma concentration of this kind of drugs occurs approximately 1 hour after administration.⁵

Volume of distribution

The serotonin antagonists and reuptake inhibitors as lorpiprazole are quickly distributed through the blood-brain-barrier getting concentrated in the brain to even higher levels than the ones found in plasma.⁵

Protein binding

The plasma protein binding of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to be very high and correspond to even 89-99% of the administered dose.⁵

Metabolism

Serotonin antagonists and reuptake inhibitors like lorpiprazole are metabolized in the liver by the CYP450 isoenzymes, mainly CYP2D6 and CYP3A4.²

Route of elimination

The elimination of drugs that fit in the category of serotonin antagonists and reuptake inhibitors like lorpiprazole is expected to have a biphasic profile in which most of the metabolized drug should be disposed of by the urine.⁵

Half-life

The estimated half-life for drugs like lorpiprazole, a serotonin antagonist and reuptake inhibitor, is in the range of 11-23 hours.⁵

Clearance

Not Available

Adverse Effects

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Toxicity

The serotonin antagonists and reuptake inhibitors' side effects are minor with rare reports of cardiotoxicity. They have been reported to cause an unbalance between the sympathetic and parasympathetic system. There are also reports regarding a potential hepatotoxic effect of this drugs.⁵

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

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.

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of sedation can be increased when Lorpiprazole is combined with 1,2-Benzodiazepine.
Abacavir	Abacavir may decrease the excretion rate of Lorpiprazole which could result in a higher serum level.
Abametapir	The serum concentration of Lorpiprazole can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Lorpiprazole can be increased when combined with Abatacept.
Abiraterone	The metabolism of Lorpiprazole can be decreased when combined with Abiraterone.

Food Interactions

Not Available

Products

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International/Other Brands: Normarex

Chemical Identifiers

UNII: 0M14O7T47Q
CAS number: 108785-69-9
InChI Key: BNRMWKUVWLKDQJ-YJBOKZPZSA-N
InChI: InChI=1S/C21H26F3N5/c22-21(23,24)16-4-2-5-17(13-16)28-11-9-27(10-12-28)8-7-19-25-26-20-18-6-1-3-15(18)14-29(19)20/h2,4-5,13,15,18H,1,3,6-12,14H2/t15-,18-/m0/s1
IUPAC Name: (1S,8R)-5-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-3,4,6-triazatricyclo[6.3.0.0²,⁶]undeca-2,4-diene
SMILES: [H][C@@]12CCC[C@]1([H])C1=NN=C(CCN3CCN(CC3)C3=CC=CC(=C3)C(F)(F)F)N1C2

References

General References

Fagiolini A, Comandini A, Catena Dell'Osso M, Kasper S: Rediscovering trazodone for the treatment of major depressive disorder. CNS Drugs. 2012 Dec;26(12):1033-49. doi: 10.1007/s40263-012-0010-5. [Article]
Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]
Elks J. and Ganellin C.R. (1990). The dictionary of drugs. Springer Science.
Clark M., Harvey R., Finkel R., Rey J. and Whalen K. (2011). Pharmacology (5th ed.). Lippincott Williams & Wilkins.
Szyndler J., Skorzewska A. and Plaznik A. (2003). Pharmacotherapy in psychiatry and neurology (3rd ed.). Institute of psychiatry and neurology.
Molecules 2016 [Link]

External Links

PubChem Compound: 20055414
PubChem Substance: 310265103
ChemSpider: 16736802
ZINC: ZINC000000537940
Wikipedia: Lorpiprazole

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count

Pharmacoeconomics

Manufacturers: Not Available
Packagers: Not Available
Dosage Forms: Not Available
Prices: Not Available
Patents: Not Available

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	138 ºC	Elks J. The Dictionary of Drugs. (1990)
logP	3.02	DrugCentral
logS	-3.63	DrugCentral

Predicted Properties

Property	Value	Source
Water Solubility	0.095 mg/mL	ALOGPS
logP	3.64	ALOGPS
logP	3.22	Chemaxon
logS	-3.6	ALOGPS
pKa (Strongest Basic)	7.57	Chemaxon
Physiological Charge	1	Chemaxon
Hydrogen Acceptor Count	4	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	37.19 Å²	Chemaxon
Rotatable Bond Count	5	Chemaxon
Refractivity	108.4 m³·mol^-1	Chemaxon
Polarizability	42.08 Å³	Chemaxon
Number of Rings	5	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	Yes	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Not Available

Spectra

Mass Spec (NIST)

Not Available

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0a4i-0000900000-9bdd45743e069cefdb8c
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0udi-0000900000-e63d94b7416cf8b434a2
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	splash10-0a4i-0002900000-a030ebd81e5c0166a3da
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0udi-0002900000-71c2f40a050270f09b68
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	splash10-004i-1049100000-477cf170ab2ae5c5343b
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	splash10-0i00-0695300000-fb32a2a8f4dce1f7eb5e
Predicted 1H NMR Spectrum	1D NMR	Not Applicable
Predicted 13C NMR Spectrum	1D NMR	Not Applicable

Chromatographic Properties

Collision Cross Sections (CCS)

Adduct	CCS Value (Å²)	Source type	Source
[M-H]-	193.79022	predicted	DeepCCS 1.0 (2019)
[M+H]+	196.14822	predicted	DeepCCS 1.0 (2019)
[M+Na]+	203.21112	predicted	DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.

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Details1. 5-hydroxytryptamine receptor 2A

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

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details2. 5-hydroxytryptamine receptor 2C

Kind: Protein
Organism: Humans
Pharmacological action: Yes
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: P28335
Uniprot Name: 5-hydroxytryptamine receptor 2C
Molecular Weight: 51820.705 Da

References

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details3. Alpha-1 adrenergic receptors (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Yes
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...

Components:

Name	UniProt ID
Alpha-1A adrenergic receptor	P35348
Alpha-1B adrenergic receptor	P35368
Alpha-1D adrenergic receptor	P25100

References

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details4. Alpha-2 adrenergic receptors (Protein Group)

Kind: Protein group
Organism: Humans
Pharmacological action: Yes
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:

Name	UniProt ID
Alpha-2A adrenergic receptor	P08913
Alpha-2B adrenergic receptor	P18089
Alpha-2C adrenergic receptor	P18825

References

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details5. Histamine H1 receptor

Kind: Protein
Organism: Humans
Pharmacological action: Yes
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

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details6. Sodium-dependent serotonin transporter

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antagonist

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

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Enzymes

Details1. Cytochrome P450 2D6

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

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

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Details2. Cytochrome P450 3A4

Kind: Protein
Organism: Humans
Pharmacological action: No
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

Jarema M, Dudek D, Landowski J, Heitzman J, Rabe-Jablonska J, Rybakowski J: [Trazodon--the antidepressant: mechanism of action and its position in the treatment of depression]. Psychiatr Pol. 2011 Jul-Aug;45(4):611-25. [Article]

Carriers

Details1. Serum albumin

Kind: Protein
Organism: Humans
Pharmacological action: No
Actions: Substrate

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

Drug created at October 16, 2015 21:28 / Updated at February 21, 2021 18:52

Lorpiprazole

Identification

Structure for Lorpiprazole (DB09195)

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Spectra

Collision Cross Sections (CCS)

Targets

References

References

Components:

References

Components:

References

References

References

Enzymes

References

References

Carriers