Ten Years of Rizatriptan: From Development to Clinical Science and Future Directions

Abstract

The year 2008 marked the 10th anniversary since rizatriptan was first launched for the acute treatment of migraine. In this article we discuss the concepts that motivated the preclinical and clinical development of rizatriptan, the clinical evidence that has driven its use over the past decade, rizatriptan's overall contribution to the field, and future directions for research.

A double-blind, randomized, multicenter, Italian study of frovatriptan versus rizatriptan for the acute treatment of migraine

“…However, with the only exception of a head-to-head randomized trial versus sumatriptan [10], frovatriptan efficacy had never been tested in comparative trials with other triptans. For this reason a study was setup to compare efficacy and safety of frovatriptan versus rizatriptan, the triptan known to provide consistent relief of migraine attacks and usually preferred over other treatments because of its speed of relief [11, 12]. …”

A facile procedure for synthesis of 3-[2-(N,N-dialkylamino)ethyl]-3-fluorooxindoles by direct fluorination of N,N-dialkyltryptamines

“…Finally, we applied this new protocol to a tryptamine-based medicinal, rizatriptan (19), which is a potent agonist toward both serotonin 5-HT 1B and 5-HT 1D receptors, and is currently used for treatment for migraine headache [16]. Reaction of 19 with 3 equiv of 5 in the presence of 1.1 equiv of AlCl 3 in MeCN/MeOH (1/1) produced 20 in 75% yield (Scheme 3).…”

Key differences between triptans relate to their pharmacokinetic profiles and available formulations

“…[1] Sleepiness, tiredness and difficulty thinking are the most common CNS adverse events observed with triptans, and may lead to patients delaying administration, resulting in decreased efficacy. Sumatriptan is also available as a rectal [10] superior in all efficacy endpoints vs PL; [11] similar in a number of efficacy endpoints to sumatriptan 100 mg; [11,12] in a meta-analysis, PF at 2 h was 24% and recurrence was 30% better than sumatriptan 100 mg; [8] has similar efficacy to sumatriptan 100 mg, zolmitriptan 2.5 mg, rizatriptan 10 mg and eletriptan 40 mg [1] More favourable tolerability in triptan-naive pts than in triptanexperienced pts [10] Best tolerated triptan vs sumatriptan 100 mg [8] Eletriptan (available as 20 and 40 mg tablets) 20 mg tablet : similar in efficacy to sumatriptan 100 mg [13] 40 mg tablet : mean 24 h recurrence 19-30%; TG 22-41%; better HR, PF and lower recurrence rate vs PL; [14,15] greater efficacy in functional response than sumatriptan 100 mg; [16] similar efficacy to almotriptan 12.5 mg, zolmitriptan 2.5 mg and rizatriptan 10 mg [14] AEs mild or moderate and transient [2,7,13] 40 mg dose has fewer AEs than sumatriptan 100 mg [16] Rizatriptan (available as 5 and 10 mg tablets, 5 and 10 mg ODT) 10 mg tablet : mean 24 h recurrence 30-47%; TG 27-40%; superior to PL in all clinical endpoints including PFR at 2 h and sustained PF at 24 h; [8,17] more headache recurrence at 24 h vs PL; [18] PF at 2 h, HR and PF at 24 h were 38%, 17% and 25% better than with sumatriptan 100 mg, respectively; [8] high consistency of efficacy, 67% for HR and 58% for PF for 3 of 3 attacks; [8] more effective than sumatriptan 50 mg and naratriptan 2.5 mg and has similar efficacy to zolmitriptan 2.5 mg, almotriptan 12.5 mg and eletriptan 40 mg [1] 10 mg ODT : TG 19-46%; perceived by some pts as providing faster pain relief [17] Better tolerated than other triptans [8] Sumatriptan ( [2,7] mean 24 h recurrence 34-38%; TG 51% 50 mg tablet : mean 24 h recurrence 32%; TG 29-36%; superior HR at 2 h vs ...…”