T3DB: Zolmitriptan

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (5)XML

Targets (5)

Record Information

Version

2.0

Creation Date

2009-07-21 20:26:34 UTC

Update Date

2014-12-24 20:25:51 UTC

Accession Number

T3D2748

Identification

Common Name

Zolmitriptan

Class

Small Molecule

Description

Zolmitriptan is only found in individuals that have used or taken this drug. It is a synthetic tryptamine derivative and appears as a white powder that is readily soluble in water. Zolmitriptan binds with high affinity to human 5-HT_1B and 5-HT_1D receptors leading to cranial blood vessel constriction. Current theories proposed to explain the etiology of migraine headache suggest that symptoms are 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 zolmitriptan for the treatment of migraine headache can most likely be attributed to the agonist effects at the 5HT1B/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.

Compound Type

Amine
Anti-Inflammatory Agent
Anti-Migraine Agent
Drug
Ester
Ether
Metabolite
Organic Compound
Selective Serotonin Agonist
Serotonin 5-HT1 Receptor Agonist
Serotonin Agonist
Serotonin Antagonist
Serotonin Receptor Agonist
Synthetic Compound
Vasoconstrictor Agent

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one
311C90
4-[[3-(2-Dimethylaminoethyl)-1H-indol-5-yl]methyl]oxazolidin-2-one
AscoTop
Nomi
ZMT
Zolmiles
zolmiptriptan
Zolmit
Zolmitriptanum
Zomig
Zomig Rapimelt
Zomigon
Zomigoro
Zomitan

Chemical Formula

C₁₆H₂₁N₃O₂

Average Molecular Mass

287.357 g/mol

Monoisotopic Mass

287.163 g/mol

CAS Registry Number

139264-17-8

IUPAC Name

(4S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one

Traditional Name

zomig

SMILES

[H][C@]1(CC2=CC3=C(NC=C3CCN(C)C)C=C2)COC(O)=N1

InChI Identifier

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

InChI Key

InChIKey=ULSDMUVEXKOYBU-ZDUSSCGKSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as tryptamines and derivatives. Tryptamines and derivatives 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

Substituents

Tryptamine
3-alkylindole
Indole
Aralkylamine
Oxazolidinone
Substituted pyrrole
Benzenoid
Oxazolidine
Pyrrole
Heteroaromatic compound
Carbamic acid ester
Carbonic acid derivative
Tertiary amine
Tertiary aliphatic amine
Oxacycle
Azacycle
Hydrocarbon derivative
Organic oxide
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Organic nitrogen compound
Carbonyl group
Amine
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

tryptamines (CHEBI:10124 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular
Membrane

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Biological Roles

serotonergic agonist

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	1.90e-01 g/L
LogP	1.6

Predicted Properties

Property	Value	Source
Water Solubility	0.19 g/L	ALOGPS
logP	2.25	ALOGPS
logP	2.04	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	13	ChemAxon
pKa (Strongest Basic)	9.55	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	2	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	57.36 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	82.44 m³·mol⁻¹	ChemAxon
Polarizability	31.65 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-0a4i-9140000000-8d3d0029a006c9f3ba49	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-000i-1390000000-5eb2470575d7a40b35dd	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-000i-0390000000-d91f1c70da42e9043a7b	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Positive	splash10-0a5l-4970000000-d6feef1af8c3d273bbe4	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 35V, Negative	splash10-000i-0090000000-c74574aba82b34fbcfc1	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0090000000-2eab59f442a95263f917	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-000l-1290000000-4b3bf33424e3bd5259dc	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00du-2910000000-46170261887fb6bb2a86	2016-08-01	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-2090000000-33a4ce8acdaace7f51cb	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9060000000-dc863874d2aa1113bab8	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9100000000-ee342e011f9a483f3bed	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-2090000000-59447660b4ff1ee0d5a8	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-9170000000-ae1576ef07f3ffa1d131	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-9320000000-d3b22cc0b99199c251b7	2021-09-22	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0090000000-85a896e022373a149d53	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-000l-0090000000-78d6b93aa92bfd05a777	2021-09-23	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-5970000000-3b90408e256cd6d8ae19	2021-09-23	View Spectrum

Toxicity Profile

Route of Exposure

Topical(nasal); Oral. Mean absolute oral bioavailability is approximately 40%. Food has no affect on the rate and extent of absorption.

Mechanism of Toxicity

Zolmitriptan binds with high affinity to human 5-HT_1B and 5-HT_1D receptors leading to cranial blood vessel constriction. Current theories proposed to explain the etiology of migraine headache suggest that symptoms are 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 zolmitriptan for the treatment of migraine headache can most likely be attributed to the agonist effects at the 5HT1B/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.

Metabolism

Hepatic. There have been three metabolites identified: indole acetic acid, N -oxide, and N-desmethyl metabolites. However, the N-desmethyl is the only active metabolite. Half Life: The mean elimination half-life of zolmitriptan and of the active N-desmethyl metabolite is 3 hours.

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Used in the acute treatment of migraine attacks with or without aura and cluster headaches.

Minimum Risk Level

Not Available

Health Effects

Serious cardiac events, including myocardial infarction migth occur. [Wikipedia]

Symptoms

Not Available

Treatment

There is no specific antidote to zolmitriptan. In cases of severe intoxication, intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. (4)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

10124

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Zolmitriptan

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Zolmitriptan

References

Synthesis Reference

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

MSDS

T3D2748.pdf

General References

Pascual J: [Mechanism of action of zolmitriptan]. Neurologia. 1998 Oct;13 Suppl 2:9-15. [9859690 ]
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. [9399012 ]
Drugs.com [Link]
RxList: The Internet Drug Index (2009). [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. 5-hydroxytryptamine receptor 1B

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 substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Gene Name:: HTR1B
Uniprot ID:: P28222
Molecular Weight:: 43567.535 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.0042 uM	Not Available	BindingDB 50033383
Dissociation	0.0015 uM	Not Available	BindingDB 50033383

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Wurch T, Palmier C, Pauwels PJ: Induction of a high-affinity ketanserin binding site at the 5-Hydroxytryptamine(1B) receptor by modification of its carboxy-terminal intracellular portion. Biochem Pharmacol. 2000 May 1;59(9):1117-21. [10704941 ]
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. [10844127 ]
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. [11513839 ]
de Almeida RM, Nikulina EM, Faccidomo S, Fish EW, Miczek KA: Zolmitriptan--a 5-HT1B/D agonist, alcohol, and aggression in mice. Psychopharmacology (Berl). 2001 Sep;157(2):131-41. [11594437 ]
Reuter U, Salomone S, Ickenstein GW, Waeber C: Effects of chronic sumatriptan and zolmitriptan treatment on 5-HT receptor expression and function in rats. Cephalalgia. 2004 May;24(5):398-407. [15096229 ]
Glen RC, Martin GR, Hill AP, Hyde RM, Woollard PM, Salmon JA, Buckingham J, Robertson AD: Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties. J Med Chem. 1995 Sep 1;38(18):3566-80. [7658443 ]
Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]

Target Details

2. 5-hydroxytryptamine receptor 1D

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 substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction.
Gene Name:: HTR1D
Uniprot ID:: P28221
Molecular Weight:: 41906.38 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.00076 uM	Not Available	BindingDB 50033383
Inhibitory	0.00092 uM	Not Available	BindingDB 50033383
Inhibitory	0.004 uM	Not Available	BindingDB 50033383
Dissociation	0.0015 uM	Not Available	BindingDB 50033383

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
Whale R, Bhagwagar Z, Cowen PJ: Zolmitriptan-induced growth hormone release in humans: mediation by 5-HT1D receptors? Psychopharmacology (Berl). 1999 Jul;145(2):223-6. [10463324 ]
Hargreaves RJ, Shepheard SL: Pathophysiology of migraine--new insights. Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. [10563228 ]
Wurch T, Pauwels PJ: Coupling of canine serotonin 5-HT(1B) and 5-HT(1D) receptor subtypes to the formation of inositol phosphates by dual interactions with endogenous G(i/o) and recombinant G(alpha15) proteins. J Neurochem. 2000 Sep;75(3):1180-9. [10936201 ]
Glen RC, Martin GR, Hill AP, Hyde RM, Woollard PM, Salmon JA, Buckingham J, Robertson AD: Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties. J Med Chem. 1995 Sep 1;38(18):3566-80. [7658443 ]
Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]
Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, Valentin JP, Halazy S: Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors. J Med Chem. 1995 Sep 1;38(18):3602-7. [7658447 ]

Target Details

3. 5-hydroxytryptamine receptor 1A

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 signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:: HTR1A
Uniprot ID:: P08908
Molecular Weight:: 46106.335 Da

Binding/Activity Constants

Type	Value	Assay Type	Assay Source
Inhibitory	0.079 uM	Not Available	BindingDB 50033383
Inhibitory	0.124 uM	Not Available	BindingDB 50033383
Dissociation	0.0018 uM	Not Available	BindingDB 50033383

References

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. [11513839 ]
Glen RC, Martin GR, Hill AP, Hyde RM, Woollard PM, Salmon JA, Buckingham J, Robertson AD: Computer-aided design and synthesis of 5-substituted tryptamines and their pharmacology at the 5-HT1D receptor: discovery of compounds with potential anti-migraine properties. J Med Chem. 1995 Sep 1;38(18):3566-80. [7658443 ]
Perez M, Fourrier C, Sigogneau I, Pauwels PJ, Palmier C, John GW, Valentin JP, Halazy S: Synthesis and serotonergic activity of arylpiperazide derivatives of serotonin: potent agonists for 5-HT1D receptors. J Med Chem. 1995 Sep 1;38(18):3602-7. [7658447 ]
Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S: Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett. 1998 Mar 17;8(6):675-80. [9871581 ]

Target Details

4. 5-hydroxytryptamine receptor 1F

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 triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:: HTR1F
Uniprot ID:: P30939
Molecular Weight:: 41708.505 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Target Details

5. 5-hydroxytryptamine receptor 4

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 is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:: HTR4
Uniprot ID:: Q13639
Molecular Weight:: 43760.975 Da

References

Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

Zolmitriptan (T3D2748)

Structure for T3D2748: Zolmitriptan

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

Binding/Activity Constants

References

References

References