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Identification
Name Rizatriptan
Accession Number DB00953 (APRD00008)
Type small molecule
Groups approved
Description

Rizatriptan is a triptan drug used for the treatment of migraine headaches. It is a selective 5-hydroxytryptamine1 receptor subtype agonist.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
MK 462 Free Base
Risatriptan
Rizatriptan benzoat
Rizatriptan benzoate
Salts Not Available
Brand names
Name Company
Maxalt
Maxalt MLT
Maxalt-MLT
Brand mixtures Not Available
Categories
  • Vasoconstrictor Agents
  • Anti-inflammatory Agents
  • Anti-migraine Agents
  • Selective Serotonin Agonists
  • Serotonin Agonists
CAS number 145202-66-0
Weight Average: 269.3449
Monoisotopic: 269.164045633
Chemical Formula C15H19N5
InChI Key InChIKey=ULFRLSNUDGIQQP-UHFFFAOYSA-N
InChI
InChI=1S/C15H19N5/c1-19(2)6-5-13-8-17-15-4-3-12(7-14(13)15)9-20-11-16-10-18-20/h3-4,7-8,10-11,17H,5-6,9H2,1-2H3
Plain Text
IUPAC Name
dimethyl({2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl})amine
SMILES
CN(C)CCC1=CNC2=C1C=C(CN1C=NC=N1)C=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tryptamines and Derivatives
Substructures
  • Indoles and Indole Derivatives
  • Triazoles
  • Pyrroles
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Heterocyclic compounds
  • Aromatic compounds
  • Tryptamines and Derivatives
  • Cyanamides
Pharmacology
Indication For treatment of acute migraine attacks with or without aura.
Pharmacodynamics Rizatriptan is a selective agonist of serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptors. It is structurally and pharmacologically related to other selective 5-HT1B/1D receptor agonists and has only a weak affinity for 5-HT1A, 5-HT5A, and 5-HT7 receptors and no significant affinity or pharmacological activity at 5-HT2, 5-HT3 or 5-HT4 receptor subtypes or at alpha1-, alpha2-, or beta-adrenergic, dopamine1,; dopamine2; muscarinic, or benzodiazepine receptors. This action in humans correlates with the relief of migraine headache. In addition to causing vasoconstriction, experimental data from animal studies show that Rizatriptan also activates 5-HT1 receptors on peripheral terminals of the trigeminal nerve innervating cranial blood vessels, which may also contribute to the antimigrainous effect of Rizatriptan in humans.
Mechanism of action Three distinct pharmacological actions have been implicated in the antimigraine effect of the triptans: (1) stimulation of presynaptic 5-HT1D receptors, which serves to inhibit both dural vasodilation and inflammation; (2) direct inhibition of trigeminal nuclei cell excitability via 5-HT1B/1D receptor agonism in the brainstem and (3) vasoconstriction of meningeal, dural, cerebral or pial vessels as a result of vascular 5-HT1B receptor agonism.
Absorption Rapid following oral administration. Bioavailability is 45%. Food has no effect on the bioavailability of rizatriptan. However, administering rizatriptan with food will delay by 1 hour the time to reach peak plasma concentration. The rate of absorption is not affected by the presence of a migraine attack.
Volume of distribution
  • 140 L [male]
  • 110 L [female]
Protein binding 14%
Metabolism Rizatriptan is metabolized by monoamine oxidase A isoenzyme (MAO-A) to an inactive indole acetic acid metabolite. In addition, several other inactive metabolites are formed. An active metabolite, N-monodesmethyl-rizatriptan, with pharmacological activity similar to that of the parent compound has been identified in small concentrations (14%) in the plasma.
Route of elimination Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism.
Half life 2-3 hours
Clearance Not Available
Toxicity Symptoms of overdose include dizziness, fainting, heart and blood vessel problems, high blood pressure, loss of bowel and bladder control, slow heartbeat, and vomiting.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Merck and co inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Wafer Oral
Prices
Unit description Cost Unit
Maxalt 12 10 mg tablet Box 333.27 USD box
Maxalt 12 5 mg tablet Box 333.27 USD box
Maxalt-MLT 3 5 mg Dispersible Tablet Box 286.96 USD box
Maxalt 9 5 mg tablet Box 203.46 USD box
Maxalt 6 5 mg tablet Box 107.44 USD box
Maxalt-MLT 3 10 mg Dispersible Tablet Box 83.32 USD box
Maxalt mlt 10 mg tablet 26.7 USD tablet
Maxalt mlt 5 mg tablet 26.7 USD tablet
Maxalt 10 mg tablet 25.31 USD tablet
Maxalt 5 mg tablet 22.98 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States 5602162 1994-02-11 2014-02-11
United States 5298520 1995-06-29 2012-06-29
Canada 2060139 1998-12-01 2012-01-28
Properties
State solid
Experimental Properties
Property Value Source
melting point 178-180 °C Not Available
water solubility 42 mg/mL (for free base) Not Available
logP 1.4 Not Available
Predicted Properties
Property Value Source
water solubility 3.38e-01 g/l ALOGPS
logP 1.67 ALOGPS
logP 1.77 ChemAxon
logS -2.9 ALOGPS
pKa (strongest acidic) 17.24 ChemAxon
pKa (strongest basic) 9.56 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 49.74 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 93.13 ChemAxon
polarizability 30 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Wellington K, Plosker GL: Rizatriptan: an update of its use in the management of migraine. Drugs. 2002;62(10):1539-74. Pubmed
  2. Wellington K, Jarvis B: Spotlight on rizatriptan in migraine. CNS Drugs. 2002;16(10):715-20. Pubmed
  3. Ikemoto F, Toru T, Aijima H, Natsumeda Y: [Rizatriptan (Maxalt), a new entity of triptan for migraine: pharmacology and therapeutic relevance] Nippon Yakurigaku Zasshi. 2004 Apr;123(4):295-302. Pubmed
  4. Villalon CM, Centurion D, Valdivia LF, De Vries P, Saxena PR: An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210. Pubmed
  5. Tfelt-Hansen P, De Vries P, Saxena PR: Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy. Drugs. 2000 Dec;60(6):1259-87. Pubmed
External Links
Resource Link
KEGG Drug D00675 Link_out
PubChem Compound 5078 Link_out
PubChem Substance 46506557 Link_out
ChemSpider 4900 Link_out
ChEBI 48273 Link_out
ChEMBL 48273 Link_out
Therapeutic Targets Database DAP000220 Link_out
PharmGKB PA451264 Link_out
IUPHAR 51 Link_out
Guide to Pharmacology 51 Link_out
Drug Product Database 2240520 Link_out
RxList http://www.rxlist.com/cgi/generic2/rizatrip.htm Link_out
Drugs.com http://www.drugs.com/cdi/rizatriptan.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/max1248.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Rizatriptan Link_out
ATC Codes
  • N02CC04
AHFS Codes
  • 28:32.28
PDB Entries Not Available
FDA label show (873 KB)
MSDS show (57.7 KB)
Interactions
Drug Interactions
Drug Interaction
Citalopram Increased risk of CNS adverse effects
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroergotamine Possible severe and prolonged vasoconstriction
Ergotamine Possible severe and prolonged vasoconstriction
Escitalopram Increased risk of CNS adverse effects
Fluoxetine Increased risk of CNS adverse effects
Fluvoxamine Increased risk of CNS adverse effects
Isocarboxazid The MAO inhibitor, isocarboxazid, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
Methysergide Possible severe and prolonged vasoconstriction
Moclobemide The MAO inhibitor, moclobemide, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
Nefazodone Increased risk of CNS adverse effects
Paroxetine Increased risk of CNS adverse effects
Phenelzine The MAO inhibitor, phenelzine, may decrease the metabolism and clearance of the serotonin 5-HT receptor agonist, rizatriptan. Concomitant therapy is contraindicated.
Propranolol Propranolol increases the effect and toxicity of rizatriptan
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine The MAO inhibitor, Tranylcypromine, may reduce the metabolism and clearance of the serotonin 5-HT1D receptor agonist, Rizatriptan. Risk of serotonin syndrome and Rizatriptan toxicity. Concomitant therapy should be avoided.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Zolmitriptan Concomitant use of two serotonin 5-HT1D receptor agonists, such as zolmitriptan and rizatriptan, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.
Food Interactions Not Available
Targets

1. 5-hydroxytryptamine 1D receptor

Pharmacological action: yes
Actions: agonist

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 inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28221 Link_out
Gene: HTR1D Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Longmore J, Hargreaves RJ, Boulanger CM, Brown MJ, Desta B, Ferro A, Schofield WN, Taylor AA, Hill RG: Comparison of the vasoconstrictor properties of the 5-HT1D-receptor agonists rizatriptan (MK-462) and sumatriptan in human isolated coronary artery: outcome of two independent studies using different experimental protocols. Funct Neurol. 1997 Jan-Feb;12(1):3-9. Pubmed
  3. Longmore J, Boulanger CM, Desta B, Hill RG, Schofield WN, Taylor AA: 5-HT1D receptor agonists and human coronary artery reactivity in vitro: crossover comparisons of 5-HT and sumatriptan with rizatriptan and L-741,519. Br J Clin Pharmacol. 1996 Oct;42(4):431-41. Pubmed
  4. Sciberras DG, Polvino WJ, Gertz BJ, Cheng H, Stepanavage M, Wittreich J, Olah T, Edwards M, Mant T: Initial human experience with MK-462 (rizatriptan): a novel 5-HT1D agonist. Br J Clin Pharmacol. 1997 Jan;43(1):49-54. Pubmed
  5. Williamson DJ, Hill RG, Shepheard SL, Hargreaves RJ: The anti-migraine 5-HT agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol. 2001 Aug;133(7):1029-34. Pubmed
  6. Wackenfors A, Jarvius M, Ingemansson R, Edvinsson L, Malmsjo M: Triptans induce vasoconstriction of human arteries and veins from the thoracic wall. J Cardiovasc Pharmacol. 2005 May;45(5):476-84. Pubmed
  7. Wellington K, Plosker GL: Rizatriptan: an update of its use in the management of migraine. Drugs. 2002;62(10):1539-74. Pubmed
  8. Wellington K, Jarvis B: Spotlight on rizatriptan in migraine. CNS Drugs. 2002;16(10):715-20. Pubmed
  9. Ikemoto F, Toru T, Aijima H, Natsumeda Y: [Rizatriptan (Maxalt), a new entity of triptan for migraine: pharmacology and therapeutic relevance] Nippon Yakurigaku Zasshi. 2004 Apr;123(4):295-302. Pubmed

2. 5-hydroxytryptamine 1B receptor

Pharmacological action: yes
Actions: agonist

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 inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P28222 Link_out
Gene: HTR1B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Wellington K, Plosker GL: Rizatriptan: an update of its use in the management of migraine. Drugs. 2002;62(10):1539-74. Pubmed
  2. Wellington K, Jarvis B: Spotlight on rizatriptan in migraine. CNS Drugs. 2002;16(10):715-20. Pubmed
  3. Ikemoto F, Toru T, Aijima H, Natsumeda Y: [Rizatriptan (Maxalt), a new entity of triptan for migraine: pharmacology and therapeutic relevance] Nippon Yakurigaku Zasshi. 2004 Apr;123(4):295-302. Pubmed
  4. Pauwels PJ, Palmier C, Dupuis DS, Colpaert FC: Interaction of 5-HT1B/D ligands with recombinant h 5-HT1A receptors: intrinsic activity and modulation by G-protein activation state. Naunyn Schmiedebergs Arch Pharmacol. 1998 May;357(5):490-9. Pubmed
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  6. Williamson DJ, Hill RG, Shepheard SL, Hargreaves RJ: The anti-migraine 5-HT agonist rizatriptan inhibits neurogenic dural vasodilation in anaesthetized guinea-pigs. Br J Pharmacol. 2001 Aug;133(7):1029-34. Pubmed
  7. Wackenfors A, Jarvius M, Ingemansson R, Edvinsson L, Malmsjo M: Triptans induce vasoconstriction of human arteries and veins from the thoracic wall. J Cardiovasc Pharmacol. 2005 May;45(5):476-84. Pubmed

3. 5-hydroxytryptamine 1F receptor

Pharmacological action: yes
Actions: agonist

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 inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P30939 Link_out
Gene: HTR1F Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. Villalon CM, Centurion D, Valdivia LF, de Vries P, Saxena PR: Migraine: pathophysiology, pharmacology, treatment and future trends. Curr Vasc Pharmacol. 2003 Mar;1(1):71-84. Pubmed
  3. Villalon CM, Centurion D, Valdivia LF, De Vries P, Saxena PR: An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210. Pubmed
  4. Wainscott DB, Johnson KW, Phebus LA, Schaus JM, Nelson DL: Human 5-HT1F receptor-stimulated [35S]GTPgammaS binding: correlation with inhibition of guinea pig dural plasma protein extravasation. Eur J Pharmacol. 1998 Jul 3;352(1):117-24. Pubmed
  5. Goadsby PJ, Classey JD: Evidence for serotonin (5-HT)1B, 5-HT1D and 5-HT1F receptor inhibitory effects on trigeminal neurons with craniovascular input. Neuroscience. 2003;122(2):491-8. Pubmed
Enzymes

1. Amine oxidase [flavin-containing] A

Actions: substrate

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 tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

UniProt ID: P21397 Link_out
Gene: MAOA Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Iwasa T, Sano H, Sugiura A, Uchiyama N, Hara K, Okochi H, Nakagawa K, Yasumori T, Ishizaki T: An in vitro interethnic comparison of monoamine oxidase activities between Japanese and Caucasian livers using rizatriptan, a serotonin receptor 1B/1D agonist, as a model drug. Br J Clin Pharmacol. 2003 Nov;56(5):537-44. Pubmed
  2. Van Haarst AD, Van Gerven JM, Cohen AF, De Smet M, Sterrett A, Birk KL, Fisher AL, De Puy ME, Goldberg MR, Musson DG: The effects of moclobemide on the pharmacokinetics of the 5-HT1B/1D agonist rizatriptan in healthy volunteers. Br J Clin Pharmacol. 1999 Aug;48(2):190-6. Pubmed

2. Cytochrome P450 1A2

Actions: substrate

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 unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sternieri E, Coccia CP, Pinetti D, Ferrari A: Pharmacokinetics and interactions of headache medications, part I: introduction, pharmacokinetics, metabolism and acute treatments. Expert Opin Drug Metab Toxicol. 2006 Dec;2(6):961-79. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19