Chemistry:Rizatriptan

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Rizatriptan, sold under the brand name Maxalt among others, is a medication used for the treatment of migraine headaches.[1][2] It is taken by mouth.[1][2] It can also be applied on the tongue.[3] It is a serotonin (5-HT) 1B/1D receptor agonist (triptan).[1][3]

Common side effects include chest pain, dizziness, dry mouth, and tingling.[2] Other side effects may include myocardial infarction, stroke, high blood pressure, serotonin syndrome, and anaphylaxis.[2] Excessive use may result in medication overuse headaches.[2] Use is not recommended during pregnancy and breastfeeding is not recommended within 24 hours after taking a dose.[4] Rizatriptan is in the triptan class and is believed to work by activating the 5-HT1 receptor.[2]

Rizatriptan was patented in 1991 and came into medical use in 1998.[5][6] It is available as a generic medication.[4] In 2023, it was the 208th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[7][8] Rizatriptan is available in combination with meloxicam as meloxicam/rizatriptan.

Medical uses

Rizatriptan is indicated to treat acute migraine attacks with or without aura.[1][3] It does not prevent future migraine attacks.[9] A 2010 review found rizatriptan to be more efficacious and tolerable than sumatriptan.[10]

Contraindications

Rizatriptan and other triptans can cause vasoconstriction, they are contraindicated in people with cardiovascular conditions.[11]

Adverse effects

Frequent adverse effects (incidence less than 10%) are dizziness, drowsiness, asthenia/fatigue, and nausea. Clinical adverse experiences were typically mild and short-lasting (2–3 hours).[11]

Interactions

Rizatriptan has an important but complex interaction with a metabolite of the beta blocker propranolol.[12] This interaction involves the enzyme monoamine oxidase A (MAO-A).[12] Due to the interaction, the dose of rizatriptan should be reduced to 5 mg when it is combined with propranolol.[12]

Pharmacology

Mechanism of action

Rizatriptan activities
Target Affinity (Ki, nM)
5-HT1A 48–500 (Ki)
>10,000 (EC50)
40% (Emax)
5-HT1B 3–138 (Ki)
1.4–234 (EC50)
74–99% (Emax)
5-HT1D 1.5–138 (Ki)
1.6–16 (EC50)
83–105% (Emax)
5-HT1E 87–316 (Ki)
6.8–870 (EC50)
107% (Emax)
5-HT1F 138–5,370 (Ki)
4.2–2,540 (EC50)
93% (Emax)
5-HT2A >10,000 (Ki)
>10,000 (EC50)
5-HT2B 257–3,090 (Ki)
3,240 (EC50)
5-HT2C >3,160 (Ki)
ND (EC50)
5-HT3 >3,160 (mouse)
5-HT4 >3,160 (guinea pig)
5-HT5A 5,500 (rat)
5-HT6 >3,160
5-HT7 1,860–>10,000 (Ki)
>10,000 (EC50)
α1A–α1D ND
α2A–α2C ND
β1–β3 ND
D1–D5 ND
H1–H4 ND
M1–M5 ND
I1, I2 ND
σ1, σ2 ND
TAAR1 ND
SERT ND
NET ND
DAT ND
Notes: The smaller the value, the more avidly the drug binds to the site. All proteins are human unless otherwise specified. Refs: [13][14][15][16][17][18][19]
[20][21][22][23][24][25][26]

Rizatriptan acts as an agonist at serotonin 5-HT1B and 5-HT1D receptors.[27] Like the other triptans sumatriptan and zolmitriptan, rizatriptan induces vasoconstriction—possibly by inhibiting the release of calcitonin gene-related peptide from sensory neurons in the trigeminal nerve.[27]

Chemistry

Rizatriptan, also known as 5-(1H-1,2,4-triazol-1-ylmethyl)-N,N-dimethyltryptamine, is a tryptamine derivative and a 5-substituted derivative of the psychedelic drug dimethyltryptamine (DMT).[28]

The experimental log P of rizatriptan is 1.4 and its predicted log P is 1.67 to 1.77.[28][29]

History

Rizatriptan was patented in 1991 and was introduced for medical use in 1998.[5][6]

Society and culture

Brand names

Brand names include Rizalt, Rizalt RPD, Rizact (India), Rizafilm,[3] Maxalt,[1] and Maxalt-MLT.[1][30][31][32]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Cite error: Invalid <ref> tag; no text was provided for refs named Maxalt FDA label
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Rizatriptan Benzoate Monograph for Professionals". American Society of Health-System Pharmacists. https://www.drugs.com/monograph/rizatriptan-benzoate.html. 
  3. ↑ 3.0 3.1 3.2 3.3 Cite error: Invalid <ref> tag; no text was provided for refs named Rizafilm FDA label
  4. ↑ 4.0 4.1 British National Formulary: BNF 76 (76 ed.). Pharmaceutical Press. 2018. pp. 473. ISBN 9780857113382. 
  5. ↑ 5.0 5.1 "Drug Approval Package: Maxalt/Rizatritan Benzoate NDA# 20864 & 20865". U.S. Food and Drug Administration (FDA). 30 March 2001. https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20864-20865.cfm. 
  6. ↑ 6.0 6.1 Analogue-based Drug Discovery. John Wiley & Sons. 2006. p. 531. ISBN 9783527607495. https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA531. 
  7. ↑ "The Top 300 of 2023". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  8. ↑ "Rizatriptan Drug Usage Statistics, United States, 2013 - 2023". https://clincalc.com/DrugStats/Drugs/Rizatriptan. 
  9. ↑ "Rizatriptan". U.S. National Library of Medicine. https://www.medlineplus.gov/druginfo/meds/a601109.html. 
  10. ↑ "Efficacy and tolerability of rizatriptan 10 mg compared with sumatriptan 100 mg: an evidence-based analysis.". Expert Rev Neurother 10 (4): 499–506. 2010. doi:10.1586/ern.10.24. PMID 20367203. 
  11. ↑ 11.0 11.1 "Ten years of rizatriptan: from development to clinical science and future directions.". Headache 49: S3–S20. 2009. doi:10.1111/j.1526-4610.2008.01335.x. PMID 19161563. 
  12. ↑ 12.0 12.1 12.2 "Migraine pharmacotherapy with oral triptans: a rational approach to clinical management". Expert Opinion on Pharmacotherapy 1 (3): 391–404. March 2000. doi:10.1517/14656566.1.3.391. PMID 11249525. 
  13. ↑ Liu, Tiqing. "BindingDB BDBM50033437 CHEMBL905::MK 462 free base::N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl-ethanamine::N,N-dimethyl-2-[5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethanamine::N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indole-3-ethanamine::RIZATRIPTAN::risatriptan"]. https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50033437. 
  14. ↑ "Pharmacology of triptans". Emerging Drugs 4 (1): 107–125. 1999. doi:10.1517/14728214.4.1.107. ISSN 1361-9195. 
  15. ↑ "Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and efficacy". Drugs 60 (6): 1259–1287. December 2000. doi:10.2165/00003495-200060060-00003. PMID 11152011. 
  16. ↑ "Current and emerging second-generation triptans in acute migraine therapy: a comparative review". J Clin Pharmacol 40 (7): 687–700. July 2000. doi:10.1177/00912700022009431. PMID 10883409. 
  17. ↑ "Success and failure of triptans". The Journal of Headache and Pain 2 (1): 3–11. 2001. doi:10.1007/s101940170040. ISSN 1129-2369. 
  18. ↑ "Coronary Side Effects of Antimigraine Drugs From Patient to Receptor". 22 December 1999. https://repub.eur.nl/pub/16171/. "Table 1.2 Receptor binding properties (pKi values) of sumatriptan and second-generation triptans at 5-HT receptors. [...]" 
  19. ↑ "Vascular Effects of Antimigraine Drugs: pharmacology of human in vitro models in migraine". 13 March 2002. https://repub.eur.nl/pub/16167/. "Table 1.2 Receptor binding properties (pKi values) of the triptans at human 5-HT receptors. [...]" 
  20. ↑ "How efficacious are 5-HT1B/D receptor ligands: an answer from GTP gamma S binding studies with stably transfected C6-glial cell lines". Neuropharmacology 36 (4-5): 499–512. 1997. doi:10.1016/s0028-3908(96)00170-0. PMID 9225275. 
  21. ↑ "Preclinical pharmacological profile of the selective 5-HT1F receptor agonist lasmiditan". Cephalalgia 30 (10): 1159–1169. October 2010. doi:10.1177/0333102410370873. PMID 20855361. 
  22. ↑ "Characterization of binding, functional activity, and contractile responses of the selective 5-HT1F receptor agonist lasmiditan". British Journal of Pharmacology 176 (24): 4681–4695. December 2019. doi:10.1111/bph.14832. PMID 31418454. "TABLE 1 Summary of pIC50 (negative logarithm of the molar concentration of these compounds at which 50% of the radioligand is displaced) and pKi (negative logarithm of the molar concentration of the Ki ) values of individual antimigraine drugs at 5‐HT receptors [...] TABLE 2 Summary of pEC50 values of cAMP (5‐HT1A/B/E/F and 5‐HT7), GTPγS (5‐HT1A/B/D/E/F), and IP (5‐HT2) assays of individual antimigraine drugs at 5‐HT receptors [...]". 
  23. ↑ Perez, M.; Halazy, S.; Pauwels, P.J.; Colpaert, F.C.; John, G.W. (1999). "F-11356". Drugs of the Future 24 (6): 0605. doi:10.1358/dof.1999.024.06.537284. http://access.portico.org/stable?au=pjbf78x6c9d. Retrieved 23 June 2025. 
  24. ↑ "Lasmiditan hydrochloride". Drugs of the Future 37 (10): 709. 2012. doi:10.1358/dof.2012.037.010.1873629. ISSN 0377-8282. http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=2&p_RefId=1873629&p_IsPs=N. Retrieved 19 June 2025. 
  25. ↑ "Evidence-based symptomatic treatment of migraine". Migraine Management. Handbook of Clinical Neurology. 199. 2024. pp. 203–218. doi:10.1016/B978-0-12-823357-3.00004-5. ISBN 978-0-12-823357-3. 
  26. ↑ "Pharmacology of the selective 5-HT(1B/1D) agonist frovatriptan". Headache 42 (Suppl 2): S47–S53. April 2002. doi:10.1046/j.1526-4610.42.s2.2.x. PMID 12028320. 
  27. ↑ 27.0 27.1 "Rizatriptan: an update of its use in the management of migraine". Drugs 62 (10): 1539–74. 2002. doi:10.2165/00003495-200262100-00007. PMID 12093318. 
  28. ↑ 28.0 28.1 "Rizatriptan". https://pubchem.ncbi.nlm.nih.gov/compound/5078. 
  29. ↑ "Rizatriptan: Uses, Interactions, Mechanism of Action". 14 June 2012. https://go.drugbank.com/drugs/DB00953. 
  30. ↑ "Rishum01_5_982075622.pdf". https://mohpublic.z6.web.core.windows.net/IsraelDrugs/Rishum01_5_982075622.pdf. 
  31. ↑ "Maxalt Oral: Uses, Side Effects, Interactions, Pictures, Warnings & More". https://www.webmd.com/drugs/2/drug-8440/maxalt-oral/details. 
  32. ↑ "Rizact 10 mg Tablet - Uses, Dosage, Side Effects, Composition". https://www.practo.com/medicine-info/rizact-10-mg-tablet-36132. 



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