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Record Information
Version2.0
Creation Date2009-07-21 20:26:34 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2748
Identification
Common NameZolmitriptan
ClassSmall Molecule
DescriptionZolmitriptan 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-HT1B and 5-HT1D 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
Thumb
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 FormulaC16H21N3O2
Average Molecular Mass287.357 g/mol
Monoisotopic Mass287.163 g/mol
CAS Registry Number139264-17-8
IUPAC Name(4S)-4-({3-[2-(dimethylamino)ethyl]-1H-indol-5-yl}methyl)-1,3-oxazolidin-2-one
Traditional Namezomig
SMILES[H][C@]1(CC2=CC3=C(NC=C3CCN(C)C)C=C2)COC(O)=N1
InChI IdentifierInChI=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 KeyInChIKey=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.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassTryptamines and derivatives
Direct ParentTryptamines 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 FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.90e-01 g/L
LogP1.6
Predicted Properties
PropertyValueSource
Water Solubility0.19 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity82.44 m³·mol⁻¹ChemAxon
Polarizability31.65 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4i-9140000000-8d3d0029a006c9f3ba49JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-1390000000-5eb2470575d7a40b35ddJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-000i-0390000000-d91f1c70da42e9043a7bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0a5l-4970000000-d6feef1af8c3d273bbe4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Negativesplash10-000i-0090000000-c74574aba82b34fbcfc1JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0090000000-2eab59f442a95263f917JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000l-1290000000-4b3bf33424e3bd5259dcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00du-2910000000-46170261887fb6bb2a86JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-2090000000-33a4ce8acdaace7f51cbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9060000000-dc863874d2aa1113bab8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-ee342e011f9a483f3bedJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-2090000000-59447660b4ff1ee0d5a8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9170000000-ae1576ef07f3ffa1d131JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-9320000000-d3b22cc0b99199c251b7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0090000000-85a896e022373a149d53JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000l-0090000000-78d6b93aa92bfd05a777JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-5970000000-3b90408e256cd6d8ae19JSpectraViewer
Toxicity Profile
Route of ExposureTopical(nasal); Oral. Mean absolute oral bioavailability is approximately 40%. Food has no affect on the rate and extent of absorption.
Mechanism of ToxicityZolmitriptan binds with high affinity to human 5-HT1B and 5-HT1D 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.
MetabolismHepatic. 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 ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed in the acute treatment of migraine attacks with or without aura and cluster headaches.
Minimum Risk LevelNot Available
Health EffectsSerious cardiac events, including myocardial infarction migth occur. [Wikipedia]
SymptomsNot Available
TreatmentThere 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
DrugBank IDDB00315
HMDB IDHMDB14460
PubChem Compound ID60857
ChEMBL IDCHEMBL1185
ChemSpider ID54844
KEGG IDC07218
UniProt IDNot Available
OMIM ID
ChEBI ID10124
BioCyc IDNot Available
CTD IDNot Available
Stitch IDZolmitriptan
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkZolmitriptan
References
Synthesis Reference

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

MSDST3D2748.pdf
General References
  1. Pascual J: [Mechanism of action of zolmitriptan]. Neurologia. 1998 Oct;13 Suppl 2:9-15. [9859690 ]
  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. [9399012 ]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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
TypeValueAssay TypeAssay Source
Inhibitory0.0042 uMNot AvailableBindingDB 50033383
Dissociation0.0015 uMNot AvailableBindingDB 50033383
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
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
TypeValueAssay TypeAssay Source
Inhibitory0.00076 uMNot AvailableBindingDB 50033383
Inhibitory0.00092 uMNot AvailableBindingDB 50033383
Inhibitory0.004 uMNot AvailableBindingDB 50033383
Dissociation0.0015 uMNot AvailableBindingDB 50033383
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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 ]
  3. Hargreaves RJ, Shepheard SL: Pathophysiology of migraine--new insights. Can J Neurol Sci. 1999 Nov;26 Suppl 3:S12-9. [10563228 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
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
TypeValueAssay TypeAssay Source
Inhibitory0.079 uMNot AvailableBindingDB 50033383
Inhibitory0.124 uMNot AvailableBindingDB 50033383
Dissociation0.0018 uMNot AvailableBindingDB 50033383
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. [11513839 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
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
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
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
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]