Identification

Name
Zolmitriptan
Accession Number
DB00315
Description

Zolmitriptan is a member of the triptan class of 5-hydroxytryptamine(5-HT)1B/1D/(1F) receptor agonists used to treat acute migraine.1,14 Sumatriptan was the first triptan to be developed, but had poor oral bioavailability and lipophilicity. This led to the development of second-generation triptans, including almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and zolmitriptan.2 Triptans can be administered alone or in combination with an NSAID like naproxen, and represent the current "gold standard" for acute migraine treatment.4

Zolmitriptan was first approved by the FDA for sale by Zeneca Pharmaceuticals under the trade name Zomig® on November 25, 1997. It is currently available in both tablet and nasal spray forms.14

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 287.3568
Monoisotopic: 287.163376931
Chemical Formula
C16H21N3O2
Synonyms
  • (S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one
  • 4-[[3-(2-dimethylaminoethyl)-1H-indol-5-yl]methyl]oxazolidin-2-one
  • Zolmitriptan
  • Zolmitriptán
  • Zolmitriptanum
External IDs
  • 311 C 90
  • BW 311 C 90

Pharmacology

Indication

Zolmitriptan is indicated for the acute treatment of migraine with or without auras in patients aged 18 and over.14

Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Zolmitriptan, like other triptans, is a serotonin (5-hydroxytryptamine; 5-HT) receptor agonist, with enhanced specificity for the 5-HT1B and 5-HT1D receptor subtypes. It is through the downstream effects of 5-HT1B/1D activation that triptans are proposed to provide acute relief of migraines.14,1,2 Zolmitriptan is also a vasoconstrictor,5 leading to possible adverse cardiovascular effects such as myocardial ischemia/infarction, arrhythmias, cerebral and subarachnoid hemorrhage, stroke, gastrointestinal ischemia, and peripheral vasospastic reactions. In addition, chest/throat/neck/jaw pain, tightness, and/or pressure has been reported, along with the possibility of medication overuse headaches and serotonin syndrome. Patients with phenylketonuria should be advised that ZOMIG-ZMT contains phenylalanine.14

Mechanism of action

Migraines are complex physiological events characterized by unilateral throbbing headaches combined with photophobia and other aversions to sensory input. Migraine attacks are generally divided into phases: the premonitory phase, which typically involves irritability, fatigue, yawning, and stiff neck; the headache phase, which lasts for between four and 72 hours; and the postdrome phase, which lasts for up to a day following resolution of pain and whose symptoms are similar to those of the premonitory phase. In addition, neurological deficits, collectively termed migraine aura, may precede the headache phase.4,3

The underlying pathophysiology of migraines is a matter of active research but involves both neurological and vascular components. The head pain associated with migraine is thought to be a consequence of activation of the nociceptive nerves comprising the trigeminocervical complex (TCC).3 Terminals of nociceptive nerves that innervate the dura matter release vasoactive peptides, such as calcitonin gene-related peptide (CGRP), resulting in cranial vasodilation. Finally, when present, migraine aura appears to correlate with a transient wave(s) of cortical depolarization, termed cortical spreading depression (CSD).6

Triptans, including zolmitriptan, are proposed to act in three ways. The main mechanism is through modulation of nociceptive nerve signalling in the central nervous system through 5-HT1B/1D receptors throughout the TCC and associated areas of the brain. In addition, triptans can enhance vasoconstriction, both through direct 5-HT1B-mediated dilation of cranial blood vessels,1,8 as well as through 5-HT1D-mediated suppression of CGRP release.3,14

Although triptans are classically described solely in terms of their effects on 5-HT1B/1D receptors, they also act as 5-HT1F agonists as well. This 5-HT subtype is also found throughout the TCC, but is not present appreciably in cerebral vasculature; the significance of triptan-mediated 5-HT1F activation is currently not well described.2 Additionally, CSD that initiates in the ipsilateral parietal region may exert its effects in a manner that relies on 5-HT1B/1D receptor activation, suggesting that triptans may have some effect on CSD-mediated symptoms.3,7

TargetActionsOrganism
A5-hydroxytryptamine receptor 1B
agonist
Humans
A5-hydroxytryptamine receptor 1D
agonist
Humans
A5-hydroxytryptamine receptor 1F
agonist
Humans
U5-hydroxytryptamine receptor 1E
agonist
Humans
N5-hydroxytryptamine receptor 7
agonist
Humans
N5-hydroxytryptamine receptor 1A
agonist
Humans
N5-hydroxytryptamine receptor 2A
agonist
Humans
N5-hydroxytryptamine receptor 2B
agonist
Humans
Absorption

Zolmitriptan tablets have a mean absolute oral bioavailability of approximately 40%, with food having no effect on the rate or extent of absorption.1,9,14 The dosing kinetics are linear over a range of 2.5 to 50 mg with 75% of the eventual Cmax being attained within 1 hour of dosing. The median Tmax for the tablet form is 1.5 hours, while for the orally disintegrating tablet form, it is 3 hours.9,14 The AUC across studies was in the range of 84.4-173.8 ng/mL*h while the Cmax was between 16 and 25.2 ng/mL.9,12

Zolmitriptan administered as a nasal spray is detected in the plasma within 2-5 minutes, compared to 10-15 minutes for the tablet form; the faster kinetics likely reflect fast absorption across the nasal mucosa.10 The bioavailability compared to the tablet is 102%, and plasma zolmitriptan concentration is maintained for 4-6 hours after intranasal delivery.10,14

The active N-desmethyl metabolite of zolmitriptan has a mean plasma concentration that is roughly two-thirds of zolmitriptan, regardless of dosage route or concentration.9,14

Volume of distribution

Zolmitriptan has a volume of distribution between 7 and 8.4 L/kg.14

Protein binding

Zolmitriptan and its active N-desmethyl metabolite remain approximately 25% bound to plasma proteins over a concentration range of 10-1000 ng/mL.9,14

Metabolism

Zolmitriptan is metabolized in the liver, and studies using cytochrome P450 inhibitors like cimetidine suggest that it is likely metabolized by CYP1A2, as well as by monoamine oxidase (MAO).14,11,13 Zolmitriptan metabolism results in three major metabolites: an active N-desmethyl metabolite (183C91) as well as inactive N-oxide (1652W92) and indole acetic acid (2161W92) metabolites.14,12,9

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Route of elimination

Zolmitriptan is primarily excreted in urine (approximately 65%) and feces (approximately 30%). Within urine, the most common form is the indole acetic acid metabolite (31%), followed by the N-oxide (7%), and N-desmethyl (4%) metabolites; the majority of zolmitriptan recovered in feces remains unchanged.14,12

Half-life

Zolmitriptan has a mean elimination half-life of approximately three hours, while its active N-desmethyl metabolite has a slightly longer (approximately 3.5 hours) half-life.14,12

Clearance

Zolmitriptan has a clearance of 31.5 mL/min/kg for oral tablets and 25.9 mL/min/kg for nasal administration; one-sixth of the clearance is renal.14

Adverse Effects
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Toxicity

Toxicity information regarding zolmitriptan is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as cardiovascular symptoms due to excessive vasoconstriction and activation of serotonergic receptors. Patients receiving a single 50 mg oral dose of zolmitriptan often experienced sedation. Symptomatic and supportive measures are recommended.14

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3---(C;T) / (T;T)T AlleleEffect Directly StudiedPatients with this genotype have an increased likelihood of responding to zolmitriptan when treating (condition: cluster headache).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 Zolmitriptan can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Zolmitriptan can be increased when combined with Abatacept.
AbirateroneThe metabolism of Zolmitriptan can be decreased when combined with Abiraterone.
AcebutololZolmitriptan may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Zolmitriptan is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Zolmitriptan is combined with Acemetacin.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Zolmitriptan.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Zolmitriptan.
AcetazolamideThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Acetazolamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Zolmitriptan is combined with Acetophenazine.
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Food Interactions
  • Take with or without food. Food does not significantly impact the oral bioavalibility of zolmitriptan.

Products

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Product Images
International/Other Brands
AscoTop (AstraZeneca) / Nomi (Square) / Zipton / Zolmiles (Actavis) / Zolmit (Beximco) / Zomigon (AstraZeneca) / Zomigoro (AstraZeneca) / Zomitan (Incepta)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Nra-zolmitriptanTabletOralNora Pharma IncNot applicableNot applicableCanada flag
ZolmitriptanTablet2.5 mgOralSanis Health Inc2015-10-14Not applicableCanada flag
ZolmitriptanTablet2.5 mgOralPro Doc Limitee2012-03-29Not applicableCanada flag
ZolmitriptanTablet5 mg/1OralImpax Generics2013-05-142019-10-31US flag
ZolmitriptanTablet2.5 mgOralJubilant Generics LimitedNot applicableNot applicableCanada flag
ZolmitriptanTablet2.5 mg/1OralImpax Generics2013-05-142019-03-31US flag0115 067120180913 8702 1n44oqt
Zolmitriptan ODTTablet, orally disintegratingOralPro Doc Limitee2012-03-29Not applicableCanada flag
Zolmitriptan ODTTablet, orally disintegratingOralSanis Health Inc2015-10-14Not applicableCanada flag
Zolmitriptan Orally DisintegratingTablet, orally disintegrating2.5 mg/1OralImpax Generics2013-05-142020-08-31US flag
Zolmitriptan Orally DisintegratingTablet, orally disintegrating5 mg/1OralImpax Generics2013-05-142019-08-31US flag
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  • Product Code
    Product Code
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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-zolmitriptan ODTTablet, orally disintegratingOralAngita Pharma Inc.2015-12-10Not applicableCanada flag
Apo-zolmitriptanTabletOralApotex Corporation2016-08-15Not applicableCanada flag
Apo-zolmitriptan RapidTablet, orally disintegratingOralApotex Corporation2016-07-22Not applicableCanada flag
Auro-zolmitriptanTabletOralAuro Pharma Inc2020-03-18Not applicableCanada flag
Ccp-zolmitriptanTabletOralCellchem Pharmaceuticals Inc.2019-01-04Not applicableCanada flag
Dom-zolmitriptanTabletOralDominion Pharmacal2013-03-12Not applicableCanada flag
Dom-zolmitriptan ODTTablet, orally disintegratingOralDominion PharmacalNot applicableNot applicableCanada flag
Ipg-zolmitriptanTabletOralMarcan Pharmaceuticals IncNot applicableNot applicableCanada flag
Jamp ZolmitriptanTabletOralJamp Pharma Corporation2020-02-21Not applicableCanada flag
Jamp-zolmitriptanTabletOralJamp Pharma Corporation2014-03-13Not applicableCanada flag
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  • Product Code
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Categories

ATC Codes
N02CC03 — Zolmitriptan
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as tryptamines and derivatives. These are compounds containing the tryptamine backbone, which is structurally characterized by an indole ring substituted at the 3-position by an ethanamine.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Indoles and derivatives
Sub Class
Tryptamines and derivatives
Direct Parent
Tryptamines and derivatives
Alternative Parents
3-alkylindoles / Aralkylamines / Substituted pyrroles / Oxazolidinones / Benzenoids / Heteroaromatic compounds / Carbamate esters / Trialkylamines / Organic carbonic acids and derivatives / Oxacyclic compounds
show 5 more
Substituents
3-alkylindole / Amine / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Heteroaromatic compound
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
tryptamines (CHEBI:10124)

Chemical Identifiers

UNII
2FS66TH3YW
CAS number
139264-17-8
InChI Key
ULSDMUVEXKOYBU-ZDUSSCGKSA-N
InChI
InChI=1S/C16H21N3O2/c1-19(2)6-5-12-9-17-15-4-3-11(8-14(12)15)7-13-10-21-16(20)18-13/h3-4,8-9,13,17H,5-7,10H2,1-2H3,(H,18,20)/t13-/m0/s1
IUPAC Name
(4S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one
SMILES
CN(C)CCC1=CNC2=CC=C(C[[email protected]]3COC(=O)N3)C=C12

References

Synthesis Reference

Islam Aminul, Bhar Chandan, Katam Sahadev, "Process for preparing optically pure zolmitriptan." U.S. Patent US20050245585, issued November 03, 2005.

US20050245585
General References
  1. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
  2. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  3. Goadsby PJ, Holland PR, Martins-Oliveira M, Hoffmann J, Schankin C, Akerman S: Pathophysiology of Migraine: A Disorder of Sensory Processing. Physiol Rev. 2017 Apr;97(2):553-622. doi: 10.1152/physrev.00034.2015. [PubMed:28179394]
  4. Becker WJ: Acute Migraine Treatment in Adults. Headache. 2015 Jun;55(6):778-93. doi: 10.1111/head.12550. Epub 2015 Apr 15. [PubMed:25877672]
  5. Feniuk W, Humphrey PP, Perren MJ, Connor HE, Whalley ET: Rationale for the use of 5-HT1-like agonists in the treatment of migraine. J Neurol. 1991;238 Suppl 1:S57-61. doi: 10.1007/bf01642908. [PubMed:1646289]
  6. Qubty W, Patniyot I: Migraine Pathophysiology. Pediatr Neurol. 2020 Feb 4. pii: S0887-8994(20)30048-5. doi: 10.1016/j.pediatrneurol.2019.12.014. [PubMed:32192818]
  7. Supronsinchai W, Hoffmans J, Akermann S, Goadsby PJ: KCl-induced repetitive cortical spreading depression inhibits trigeminal neuronal firing mediated by 5-HT1B/1D and opioid receptor J Headache Pain. 2013 Feb 21;14(Suppl 1):P69.
  8. Longmore J, Shaw D, Smith D, Hopkins R, McAllister G, Pickard JD, Sirinathsinghji DJ, Butler AJ, Hill RG: Differential distribution of 5HT1D- and 5HT1B-immunoreactivity within the human trigemino-cerebrovascular system: implications for the discovery of new antimigraine drugs. Cephalalgia. 1997 Dec;17(8):833-42. doi: 10.1046/j.1468-2982.1997.1708833.x. [PubMed:9453271]
  9. Dixon R, Warrander A: The clinical pharmacokinetics of zolmitriptan. Cephalalgia. 1997 Oct;17 Suppl 18:15-20. doi: 10.1177/0333102497017S1803. [PubMed:9399013]
  10. Tepper SJ, Chen S, Reidenbach F, Rapoport AM: Intranasal zolmitriptan for the treatment of acute migraine. Headache. 2013 Sep;53 Suppl 2:62-71. doi: 10.1111/head.12181. [PubMed:24024604]
  11. Dixon R, French S, Kemp J, Sellers M, Yates R: The metabolism of zolmitriptan: effects of an inducer and an inhibitor of cytochrome p450 on its pharmacokinetics in healthy volunteers. Clin Drug Investig. 1998;15(6):515-22. [PubMed:18370509]
  12. Seaber E, On N, Dixon RM, Gibbens M, Leavens WJ, Liptrot J, Chittick G, Posner J, Rolan PE, Pack RW: The absolute bioavailability and metabolic disposition of the novel antimigraine compound zolmitriptan (311C90). Br J Clin Pharmacol. 1997 Jun;43(6):579-87. doi: 10.1046/j.1365-2125.1997.00614.x. [PubMed:9205817]
  13. Wild MJ, McKillop D, Butters CJ: Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. Xenobiotica. 1999 Aug;29(8):847-57. [PubMed:10553725]
  14. FDA Approved Drug Products: ZOMIG/ZOMIG-ZMT (zolmitriptan) oral tablets and nasal spray [Link]
Human Metabolome Database
HMDB0014460
KEGG Drug
D00415
KEGG Compound
C07218
PubChem Compound
60857
PubChem Substance
46506452
ChemSpider
54844
BindingDB
50033383
RxNav
135775
ChEBI
10124
ChEMBL
CHEMBL1185
ZINC
ZINC000000015515
Therapeutic Targets Database
DAP000077
PharmGKB
PA451975
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Zolmitriptan
AHFS Codes
  • 28:32.28 — Selective Serotonin Agonists
FDA label
Download (101 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherWorkplace Migraine Treatment1
4CompletedTreatmentAcute Migraine1
4CompletedTreatmentMigraine2
4Unknown StatusTreatmentCluster Headache1
3CompletedTreatmentMigraine4
2, 3CompletedTreatmentAcute Migraine1
2, 3RecruitingTreatmentCluster Headache1
1CompletedBasic ScienceMigraine1
1CompletedTreatmentMigraine4
Not AvailableCompletedNot AvailableMigraine Disorders3

Pharmacoeconomics

Manufacturers
  • Astrazeneca pharmaceuticals lp
  • Ipr pharmaceuticals inc
Packagers
  • AstraZeneca Inc.
  • Cima Laboratories Inc.
  • IPR Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Promex Medical Inc.
  • Stat Rx Usa
Dosage Forms
FormRouteStrength
Tablet, film coatedOral2.5 MG
Tablet, orally disintegratingOral2.5 MG
Tablet, film coatedOral5 MG
Tablet, orally disintegratingOral5 MG
Tablet, multilayer, extended releaseOral
TabletOral
Tablet, film coatedOral2.5 mg/1
Tablet, film coatedOral5 mg/1
Tablet, orally disintegratingOral
Tablet, coatedOral2.5 MG
Tablet, coatedOral5 MG
Tablet, film coatedOral
TabletOral2.5 MG
TabletOral5 MG
SolutionIntrasinal; Nasal5 mg
Spray, meteredNasal2.5 mg/1
Spray, meteredNasal5 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
SprayNasal2.5 mg
SprayNasal5 mg
SprayNasal; Oral
Tablet, orally disintegratingOral2.5 mg/1
Tablet, orally disintegratingOral5 mg/1
Prices
Unit descriptionCostUnit
Zomig 6 5 mg Solution 1 Box = 6 Single Use Bottles235.62USD bottle
Zomig ZMT 6 2.5 mg Dispersible Tablet Box159.66USD box
Zomig 6 2.5 mg tablet 1 Box = 6 tablet147.23USD box
Zomig 3 5 mg tablet Box93.49USD box
Zomig ZMT 3 5 mg Dispersible Tablet Box88.21USD box
Zomig 5 mg nasal spray37.76USD each
Zomig 5 mg tablet28.82USD tablet
Zomig zmt 5 mg tablet28.27USD tablet
Zomig 2.5 mg tablet26.08USD tablet
Zomig zmt 2.5 mg tablet25.59USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5466699No1995-11-142012-11-14US flag
CA2572508No2010-03-302016-08-02Canada flag
CA2064815No1999-11-162011-06-06Canada flag
US7220767Yes2007-05-222021-05-28US flag
US6750237Yes2004-06-152021-05-28US flag
Additional Data Available
  • Filed On
    Filed On
    Available for Purchase

    The date on which a patent was filed with the relevant government.

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Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)136https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/zomig-product-monograph-en.pdf
water solubility1.3 mg/mlhttps://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/zomig-product-monograph-en.pdf
logP1.792https://www.sigmaaldrich.com/MSDS/MSDS/DisplayMSDSPage.do?country=CA&language=en&productNumber=SML0248&brand=SIGMA&PageToGoToURL=https%3A%2F%2Fwww.sigmaaldrich.com%2Fcatalog%2Fproduct%2Fsigma%2Fsml0248%3Flang%3Den
pKa9.64https://www.astrazeneca.ca/content/dam/az-ca/downloads/productinformation/zomig-product-monograph-en.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.19 mg/mLALOGPS
logP2.25ALOGPS
logP2.04ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)13ChemAxon
pKa (Strongest Basic)9.55ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.36 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity82.44 m3·mol-1ChemAxon
Polarizability31.65 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.8956
Caco-2 permeable-0.8957
P-glycoprotein substrateSubstrate0.6888
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.8383
Renal organic cation transporterNon-inhibitor0.7674
CYP450 2C9 substrateNon-substrate0.8051
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5822
CYP450 1A2 substrateNon-inhibitor0.6189
CYP450 2C9 inhibitorNon-inhibitor0.8989
CYP450 2D6 inhibitorNon-inhibitor0.8281
CYP450 2C19 inhibitorNon-inhibitor0.831
CYP450 3A4 inhibitorNon-inhibitor0.8481
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9263
Ames testNon AMES toxic0.7651
CarcinogenicityNon-carcinogens0.9641
BiodegradationNot ready biodegradable0.9961
Rat acute toxicity2.5965 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9301
hERG inhibition (predictor II)Non-inhibitor0.8949
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-1390000000-5eb2470575d7a40b35dd
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0390000000-d91f1c70da42e9043a7b

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Zolmitriptan activation of 5-HT1B/1D receptors is central to the proposed mechanism of action.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Le Grand B, Panissie A, Perez M, Pauwels PJ, John GW: Zolmitriptan stimulates a Ca(2+)-dependent K(+) current in C6 glioma cells stably expressing recombinant human 5-HT(1B) receptors. Eur J Pharmacol. 2000 Jun 2;397(2-3):297-302. [PubMed:10844127]
  2. Johnson DE, Rollema H, Schmidt AW, McHarg AD: Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain. Eur J Pharmacol. 2001 Aug 17;425(3):203-10. [PubMed:11513839]
  3. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
  4. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  5. FDA Approved Drug Products: ZOMIG/ZOMIG-ZMT (zolmitriptan) oral tablets and nasal spray [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Zolmitriptan activation of 5-HT1B/1D receptors is central to the proposed mechanism of action.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1D
Uniprot ID
P28221
Uniprot Name
5-hydroxytryptamine receptor 1D
Molecular Weight
41906.38 Da
References
  1. Johnson DE, Rollema H, Schmidt AW, McHarg AD: Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain. Eur J Pharmacol. 2001 Aug 17;425(3):203-10. [PubMed:11513839]
  2. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
  3. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  4. FDA Approved Drug Products: ZOMIG/ZOMIG-ZMT (zolmitriptan) oral tablets and nasal spray [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
Curator comments
Zolmitriptan activation of 5-HT1F receptors may have clinical relevance, as they represent a target for a new class of serotonin receptor agonists known as ditans.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name
HTR1F
Uniprot ID
P30939
Uniprot Name
5-hydroxytryptamine receptor 1F
Molecular Weight
41708.505 Da
References
  1. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  2. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
  3. FDA Approved Drug Products: ZOMIG/ZOMIG-ZMT (zolmitriptan) oral tablets and nasal spray [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Curator comments
Zolmitriptan binds to 5-HT1E receptors roughly as well as to 5-HT1F receptors; the significance, if any, of this is currently unkown.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name
HTR1E
Uniprot ID
P28566
Uniprot Name
5-hydroxytryptamine receptor 1E
Molecular Weight
41681.57 Da
References
  1. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  2. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
Zolmitriptan binds more weakly to 5-HT7 receptors than to 5-HT1B/1D/1E/1F receptors.
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
Zolmitriptan binding to 5-HT1A/2A/2B receptors is weak, but still detectable; the clinical relevance of this binding is unclear but likely unimportant for the intended effect of relieving migraine symptoms.
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. Johnson DE, Rollema H, Schmidt AW, McHarg AD: Serotonergic effects and extracellular brain levels of eletriptan, zolmitriptan and sumatriptan in rat brain. Eur J Pharmacol. 2001 Aug 17;425(3):203-10. [PubMed:11513839]
  2. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
  3. Martin GR: Pre-clinical pharmacology of zolmitriptan (Zomig; formerly 311C90), a centrally and peripherally acting 5HT1B/1D agonist for migraine. Cephalalgia. 1997 Oct;17 Suppl 18:4-14. [PubMed:9399012]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
Zolmitriptan binding to 5-HT1A/2A/2B receptors is weak, but still detectable; the clinical relevance of this binding is unclear but likely unimportant for the intended effect of relieving migraine symptoms.
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. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Agonist
Curator comments
Zolmitriptan binding to 5-HT1A/2A/2B receptors is weak, but still detectable; the clinical relevance of this binding is unclear but likely unimportant for the intended effect of relieving migraine symptoms.
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Rubio-Beltran E, Labastida-Ramirez A, Villalon CM, MaassenVanDenBrink A: Is selective 5-HT1F receptor agonism an entity apart from that of the triptans in antimigraine therapy? Pharmacol Ther. 2018 Jun;186:88-97. doi: 10.1016/j.pharmthera.2018.01.005. Epub 2018 Jan 17. [PubMed:29352859]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Curator comments
CYP1A2 is likely the main metabolic enzyme for zolmitriptan metabolism in human liver, including to the N-desmethyl metabolite that is between 2 and 6 times more active against 5-HT1B/1D receptors.
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. Yu LS, Yao TW, Zeng S: In vitro metabolism of zolmitriptan in rat cytochromes induced with beta-naphthoflavone and the interaction between six drugs and zolmitriptan. Chem Biol Interact. 2003 Dec 15;146(3):263-72. [PubMed:14642738]
  2. Wild MJ, McKillop D, Butters CJ: Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. Xenobiotica. 1999 Aug;29(8):847-57. [PubMed:10553725]
  3. Dixon R, French S, Kemp J, Sellers M, Yates R: The metabolism of zolmitriptan: effects of an inducer and an inhibitor of cytochrome p450 on its pharmacokinetics in healthy volunteers. Clin Drug Investig. 1998;15(6):515-22. [PubMed:18370509]
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Curator comments
MAO-A is thought to be involved in the transformation of the active N-desmethyl metabolite to the inactive indole acetic acid metabolite. Inhibition of MAO-A in patients taking zolmitriptan may result in altered pharmacokinetics.
General Function
Serotonin binding
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOA
Uniprot ID
P21397
Uniprot Name
Amine oxidase [flavin-containing] A
Molecular Weight
59681.27 Da
References
  1. Rolan P: Potential drug interactions with the novel antimigraine compound zolmitriptan (Zomig, 311C90). Cephalalgia. 1997 Oct;17 Suppl 18:21-7. [PubMed:9399014]
  2. Wild MJ, McKillop D, Butters CJ: Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. Xenobiotica. 1999 Aug;29(8):847-57. [PubMed:10553725]
  3. Med-Psych Interactions Review: Triptans [File]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
No
Curator comments
P-glycoprotein may play a role in zolmatriptan absorption in the intestinal tract.
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. Yu L, Zeng S: Transport characteristics of zolmitriptan in a human intestinal epithelial cell line Caco-2. J Pharm Pharmacol. 2007 May;59(5):655-60. doi: 10.1211/jpp.59.5.0005. [PubMed:17524230]

Drug created on June 13, 2005 07:24 / Updated on November 25, 2020 15:47

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