ZOLMITRIPTAN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H21N3O2
Molecular Weight	287.3568
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN(C)CCC1=CNC2=C1C=C(C[C@H]3COC(=O)N3)C=C2

InChI

InChIKey=ULSDMUVEXKOYBU-ZDUSSCGKSA-N

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

HIDE SMILES / InChI

Molecular Formula	C16H21N3O2
Molecular Weight	287.3568
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Zolmitriptan (Zomig; formerly 311C90) is a novel 5-hydroxytryptamine (5HT)1B/1D receptor agonist with proven efficacy in the acute treatment of migraine with or without preceding aura. The N-desmethyl metabolite also has high affinity for 5-HT1B/1D and moderate affinity for 5-HT1A receptors. Migraines are likely due to local cranial vasodilatation and/or to the release of sensory neuropeptides (vasoactive intestinal peptide, substance P and calcitonin gene-related peptide) through nerve endings in the trigeminal system. The therapeutic activity of Zomig for the treatment of migraine headache is thought to be due to the agonist effects at the 5-HT1B/1D receptors on intracranial blood vessels (including the arterio-venous anastomoses) and sensory nerves of the trigeminal system, which result in cranial vessel constriction, and inhibition of pro-inflammatory neuropeptide release.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1d (5-HT1d) receptor 52	Agonist 2,678
Serotonin 1b (5-HT1b) receptor 46	Agonist 2,678

Conditions

Condition	Modality	Targets	Highest Phase	Product
Migraine with aura 11	Palliative		Approved 8,429	ZOMIG
Migraine without aura 7	Palliative		Approved 8,429	ZOMIG

C_max

Value	Dose	Analyte	Population
3.3 ng/mL	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
3.8 ng/mL	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
5.6 ng/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
9 ng/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
5.8 ng/mL	0.925 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
10 ng/mL	1.475 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
10.6 ng/mL	1.85 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
22.2 ng/mL	2.95 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
4.4 ng/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
9.9 ng/mL	10 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
17.7 ng × h/mL	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
21.3 ng × h/mL	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
30.9 ng × h/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
54.8 ng × h/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
16.8 ng × h/mL	0.925 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
32.4 ng × h/mL	1.475 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
32.5 ng × h/mL	1.85 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
71.2 ng × h/mL	2.95 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
23.9 ng × h/mL	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
55.7 ng × h/mL	10 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
2.29 h	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
2.56 h	2.5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
2.6 h	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
2.82 h	5 mg single, oral	ZOLMITRIPTAN plasma	Homo sapiens
2.1 h	0.925 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
2.5 h	1.475 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
2.32 h	1.85 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens
2.66 h	2.95 mg single, intravenous	ZOLMITRIPTAN plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
75%	unknown, unknown		ZOLMITRIPTAN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
5 mg single, intranasal Highest studied dose	unhealthy, 41.7 ± 10.4	Disc. AE: Taste abnormality, Migraine aggravated...
50 mg single, oral Overdose	unhealthy	Other AEs: Sedation...
5 mg single, oral Recommended	unhealthy	Disc. AE: Arrhythmia, Cerebral hemorrhage...

Showing 1 to 3 of 3 entries

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AEs

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AE	Significance	Dose	Population
Migraine aggravated	0.4% Disc. AE	5 mg single, intranasal Highest studied dose	unhealthy, 41.7 ± 10.4
Taste abnormality	0.4% Disc. AE	5 mg single, intranasal Highest studied dose	unhealthy, 41.7 ± 10.4
Sedation		50 mg single, oral Overdose	unhealthy
Arrhythmia	Disc. AE	5 mg single, oral Recommended	unhealthy
Cerebral hemorrhage	Disc. AE	5 mg single, oral Recommended	unhealthy

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737	substrate 1,037	substrate 1,217 inhibitor 1,852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1,524	CYP2C19 991 CYP1A2 1,054 P-gp 1,537 OATP1A2 62

Drug as perpetrator

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Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1,891	inhibitor 3,277	weak
CYP1A2 1,692	inhibitor 3,277	yes		yes (co-administration study)

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Drug as victim

Show entries

Target	Modality	Activity	Metabolite
CYP1A2 1,054	substrate 3,367	no	N-desmethyl-zolmitriptan 1
CYP2C9 1,037	substrate 3,367	no	N-desmethyl-zolmitriptan 1
CYP2D6 1,217	substrate 3,367	no	N-desmethyl-zolmitriptan 1
CYP2C19 991	substrate 3,367	weak
CYP2C19 991	substrate 3,367	weak	N-desmethyl-zolmitriptan 1

Showing 1 to 5 of 11 entries

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:10124	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:10124
ChemicalBook	CB3313219	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3313219
eMolecules	2729142	https://www.emolecules.com/cgi-bin/more?vid=2729142
MolPort	MolPort-003-666-626	https://www.molport.com/shop/molecule-link/MolPort-003-666-626
Selleck Chemicals	Zolmitriptan(Zomig)	http://www.selleckchem.com/products/Zolmitriptan(Zomig).html

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PubMed

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Title	Date	PubMed
Pharmacological analysis of the haemodynamic effects of 5-HT1B/D receptor agonists in the normotensive rat.	1998 Jan	9489607
[Mechanism of action of zolmitriptan].	1998 Oct	9859690
Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in the acute oral treatment of migraine: a double-blind, randomised, three-attack study.	2002	11844897
Transcranial Doppler in migraine attacks before and after treatment with oral zolmitriptan or sumatriptan.	2003 Jan	12864759
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942

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Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting dose of ZOMIG (zolmitriptan) is 1.25 mg or 2.5 mg. The 1.25 mg dose can be achieved by manually breaking the functionally-scored 2.5 mg tablet in half. The maximum recommended single dose of ZOMIG is 5 mg.

Route of Administration: Oral

In Vitro Use Guide

Stimulation of a Ca(2+)-dependent K(+) current by zolmitriptan was investigated in C6 glioma cells stably expressing recombinant human 5-HT(1B) receptors. Outward K(+) currents (I(K)) were examined in non-transfected C6 glioma cells and in cells expressing cloned human 5-HT(1B) receptors using the patch-clamp technique in the whole-cell configuration. In C6 glioma cells expressing recombinant human 5-HT 1B) receptor, zolmitriptan increased I(K) in a concentration-dependent manner (maximum increase 16.3+/-7.8%, n=5, p<0.001) with a pD(2) value (geometric mean with 95% confidence intervals) of 7.03 (7.90-6.10). Zolmitriptan failed to elicit increases in I(K) in non-transfected C6 cells.