Disease relevance of Risatriptan

• Within-patient consistency of response of rizatriptan for treating migraine [1].
• The most common adverse events associated with rizatriptan in recent randomised trials were asthenia/fatigue, dizziness, somnolence and nausea [2].
• The incidence of chest pain was similar after the administration of rizatriptan, zolmitriptan or naratriptan (2 to 4%) [2].
• At 2 h, rizatriptan 10 mg was significantly more effective than placebo for pain relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea, photophobia, phonophobia and functional disability [3].
• Review of the outcomes of 25 prospective pregnancy reports in the Pregnancy Registry and reports from other sources does not suggest that treatment with rizatriptan predisposes patients to spontaneous abortions or congenital anomalies [4].

High impact information on Risatriptan

• Effects of 5-HT1B/1D receptor agonist rizatriptan on cerebral blood flow and blood volume in normal circulation [5].
• CONCLUSION: Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response [6].
• OBJECTIVE: To compare the efficacy of oral rizatriptan 10 mg with oral doses of sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures [6].
• In early clinical trials, rizatriptan was shown to have good bioavailability and favorable effects on quality of life [7].
• A placebo-controlled crossover study of rizatriptan in the treatment of multiple migraine attacks. Rizatriptan Multiple Attack Study Group [8].

Chemical compound and disease context of Risatriptan

• Oral therapy for migraine: comparisons between rizatriptan and sumatriptan. A review of four randomized, double-blind clinical trials [9].
• Similar pattern of pain exacerbation was also observed in migraine attacks treated with oral formulation of almotriptan, eletriptan, rizatriptan, and zolmitriptan [10].
• Although well designed studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would further define the position of rizatriptan, current data suggest rizatriptan should be considered as a first-line treatment option in the management of migraine [2].
• Preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute treatment of migraine [11].
• Forty patients with migraine consecutively seen in our clinic were randomized to treat two consecutive moderate or severe attacks with one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two attacks with the same triptan and placebo, in counterbalanced order [12].

Biological context of Risatriptan

• Chest pain was reported by 1 to 3% of rizatriptan recipients and by 3 to 6% of patients receiving sumatriptan (25, 50 or 100 mg); clinically significant effects on ECG parameters, heart rate or blood pressure were not observed with rizatriptan [13].
• Neurogenic dural vasodilation was also blocked by the 5-HT(1B/1D) agonist rizatriptan (100 microg kg(-1)) with estimated plasma levels commensurate with concentrations required for anti-migraine efficacy in patients [14].
• For the commonly prescribed antimigraine drug rizatriptan, inhalation of these particles results in nearly instantaneous systemic drug action [15].
• Merck & Co., Inc. evaluates outcomes of the use of rizatriptan during pregnancy through a Pregnancy Registry in the United States (US) and spontaneous reports for pregnancies reported from sources outside the US [4].
• In naratriptan-, rizatriptan-, and sumatriptan-treated animals, jugular venous oxygen saturation decreased dose dependently (geometric mean ED50 values of 3.1, 17.9, and 16.0 microg/kg, respectively) concomitantly with increases in carotid vascular resistance [16].

Anatomical context of Risatriptan

• Sumatriptan, rizatriptan, and zolmitriptan (10 microM) stimulated [35S]GTPgammaS binding in the hippocampus by 20-50% [17].
• Rizatriptan did not reverse the dural dilation evoked by CGRP indicating an action on presynaptic receptors located on trigeminal sensory fibres innervating dural blood vessels [14].
• In addition, neurogenic dural vasodilation was also blocked by the selective 5-HT(1D) agonist PNU-142633 (100 microg kg(-1)) but not by the 5-HT(1F) agonist LY334370 (3 mg kg(-1)) suggesting that rizatriptan blocks neurogenic vasodilation via an action on 5-HT(1D) receptors located on perivascular trigeminal nerves to inhibit CGRP release [14].
• RESULTS: 5-HT, rizatriptan and sumatriptan were potent vasoconstrictors in human isolated middle meningeal artery (EC50 values=32, 90 and 71 nM, respectively) [18].
• 5. The present study (using a 'cross-over' experimental protocol) confirms our previous observation that rizatriptan is less effective than sumatriptan in causing contraction of human isolated coronary artery [19].

Associations of Risatriptan with other chemical compounds

• Four randomized clinical trials have compared the effects of oral sumatriptan with those of oral rizatriptan [9].
• CGRP and NKA levels measured before rizatriptan administration were significantly higher in responders than in non-responders (P < 0.0001 and P < 0.002, respectively) [20].
• RESULTS: In the base-case analysis, the mean CERs for almotriptan 12.5 mg and rizatriptan 10 mg were 91.12 dollars and 131.26 dollars, respectively, per attack at which SNAE was achieved after treatment [21].
• Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery [22].
• In vitro incubations showed that propranolol, but not other beta-adrenoceptor blockers significantly inhibited the production of the indole-acetic acid metabolite of rizatriptan and sumatriptan [23].

Gene context of Risatriptan

• We aimed to assess the MAO type A (MAO-A) involvement in the metabolic pathway of rizatriptan (RIZ), an antimigraine 5-hydroxytryptamine (5-HT)1B/1D agonist, and the interethnic difference in MAO activities between Caucasians and Japanese using RIZ as a model drug in in vitro experiments [24].
• Some triptans have the potential for significant drug-drug interactions (sumatriptan, rizatriptan, and zomitriptan and monoamine oxidase inhibitors; rizatriptan and propanolol; zolmitriptan and cimetidine; and eletriptan and CYP3A4 metabolized medications and p-glycoprotein pump inhibitors) [25].
• In the five patients with autonomic signs among rizatriptan responders, detectable VIP levels were found at baseline [20].
• 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 [24].
• Rizatriptan is a novel 5-HT1D/1B agonist for relief of migraine headache [26].

Analytical, diagnostic and therapeutic context of Risatriptan

• The percentages of patients who responded in a specified number of attacks after treatment with rizatriptan were calculated [1].
• A visual analog scale (VAS) method of assessing headache pain was compared with a standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, double-blind, clinical trial involving 792 treated migraine outpatients who received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or severe headache [27].
• Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials [3].
• Data from seven randomized, placebo-controlled, double-blind phase III clinical trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n = 2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for the acute treatment of a migraine attack [3].
• Urinary excretion of triazolomethyl-indole-3-acetic acid after i.v. and oral administrations of rizatriptan accounted for 35 and 51% of the dose, respectively, whereas the corresponding values for rizatriptan-N(10)-oxide were 4 and 2% of the dose [28].

References