Disease relevance of D00675

• BACKGROUND: Rizatriptan (MK-462) is a new 5-hydroxytryptamine1D (serotonin1D; 5-HT1D) receptor agonist for the acute treatment of migraine that has improved pharmacokinetic properties compared with sumatriptan succinate [1].
• The most common adverse events associated with MK-462 were drowsiness (20 mg 12%; 40 mg 44%; placebo 24%), dry mouth (40 mg 36%; placebo 19%), and lightheadedness/dizziness (40 mg 17%; placebo 10%) [2].

High impact information on D00675

• Preliminary data of new serotonin1D receptor agonists, such as 311C90 and MK-462 are promising in terms of increased efficacy after oral administration, but side-effect profile and incidence of headache recurrence are similar to those observed after the use of sumatriptan [3].
• Pilot study of MK-462 in migraine [2].
• Rizatriptan (MAXALT), a potent, oral 5-HT1B/1D agonist with a rapid onset of action, is available now for the acute treatment of migraine [4].
• Initial human experience with MK-462 (rizatriptan): a novel 5-HT1D agonist [5].
• Administration of either MK-462 or sumatriptan produced maximal mean elevations of 5-10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK-462, consistent with more rapid absorption [5].

Chemical compound and disease context of D00675

• Rizatriptan (Maxalt; Maxalt-MLT; Maxalt-Melt) is an oral serotonin 5-HT(1B/1D) receptor agonist (triptan) used in the acute treatment of migraine with or without aura in adults [6].

Biological context of D00675

• The assay has been applied to study the pharmacokinetics of MK-0462 after simultaneous oral and intravenous administration of the drug and its stable-isotope-labelled analogue to dogs [7].
• The use of stable isotope labeling and liquid chromatography/tandem mass spectrometry techniques to study the pharmacokinetics and bioavailability of the antimigraine drug, MK-0462 (rizatriptan) in dogs [7].
• Although administration of a standard breakfast prior to dosing increased the AUC value (by approximately 20%) of MK-462 and delayed its absorption, there were no significant effects of the meal on the values of Cmax and apparent t1/2 of MK-462 [8].
• The disposition kinetics of MK-462 were linear for IV doses up to and including 60 micrograms kg-1 [8].
• Pharmacokinetics and food interaction of MK-462 in healthy males [8].

Anatomical context of D00675

• 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 [9].

Gene context of D00675

• AIMS: The new 5-HT1B/1D agonist rizatriptan (MK-0462) has recently been registered for the treatment of migraine [10].

Analytical, diagnostic and therapeutic context of D00675

• 1. MK-462 (N,N-dimethyl-2-[5-(1,2,4-triazol-1-ylmethyl)-1H- indol-3-yl]ethylamine) is a novel selective 5-HT1D-receptor agonist which in clinical trials has been shown to be an effective antimigraine agent [11].
• The pharmacokinetics and tolerability of intravenous (i.v.) rizatriptan (MK-0462), a novel 5-HT1D/1B receptor agonist for the acute oral treatment of migraine, were examined in an open, single-dose, four-period, randomized crossover study in healthy females [12].

References