Initial human experience with MK‐462 (rizatriptan): a novel 5=HT_ID agonist

Abstract

A i m W e evaluated the pharmacokmetics and pharniacodynamics of oral MK-462 in comparison with oral sumatriptan in healthy male volunteers. Metlzods Sixteen healthy male volunteers were studied in a rising, single dose, alternating panel design with eight subjects per panel. Matching placebo was administered to two of eight study subjects at each dose level of MK-462 in a randomized, double-blind fashion.Results MK-462 was rapidly absorbed with a median t,, of 1.3 h (range 1-3 h) vs a tmaX for sumatriptan of 2.5 h (range 1-4 h, P<0.001). Administration of either MK-462 or sumatriptan produced maximal mean elevations of 5-10mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK-462, consistent with more rapid absorption. Both MK-462 and sumatriptan provoked mdd increases in serum growth hormone without any effect on serum prolactin concentrations. T h e most commonly reported symptom following MK-462 was drowsiness. Coriclirsions These results indicate that the novel 5-HT1, agonist, MK-462, is rapidly absorbed following oral administration and warrants further investigation of its utility in the treatment of acute migraine.

Zolmitriptan (a 5-HT1B/1D receptor agonist with central action) does not increase symptoms in obsessive compulsive disorder

“…Probably this is caused by the increase of the standard deviation (inter-individual variability) that occurred concomitant with the increase of GH levels and the small sample size which could have obscured a clinical effect. A study by Whale et al (1999) revealed that 5 mg zolmitriptan increases GH release in healthy subjects similar to the effect of sumatriptan (Boeles et al 1997;Sciberras et al 1997). Another explanation for the lack of increase in GH levels in our study could be that there is a blunted GH response in OCD patients.…”

“…Different studies found an increase in plasma GH levels in healthy subjects after the use of sumatriptan (Boeles et al 1997;Sciberras et al 1997). Other studies with sumatriptan compared healthy subjects with patients and found blunted GH responses in patients with seasonal affective disorder and depression (Yatham et al 1997a,b;Cleare et al 1998).…”

The Comparıson Of Trıptans, Nsaıd Or Combınatıon On Mıgraıne Attack Treatment

“…En fazla plazma konsantrasyonuna oral olarak 5-10 mg tek doz uygulamada 30-70 nM doza ulaşılmaktadır. [23] Rizatriptanın vazokonstrüktor etkisi 5-HT1B reseptörü üzerinden sağladığı düşünülmektedir. [20] Sağlıklı katılımcılar üzerinde yapılan bir çalışmada rizatriptan belirgin şekilde beyin kan akımını azaltmış, arterden kapillere geçen kan hacmini geniş arterler üzerindeki vazokonstrüksü-yon etkisiyle azaltmış, küçük arterlerin otoregulatuvar sistemlerinde değişikliğe sebep olmamıştır.…”

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

“…52 A subsequent study in migraine patients showed that the pharmacokinetics of rizatriptan were similar during a migraine attack and outside an attack. 53 The key trials comprising the phase 2 and phase 3 programs are summarized in Table 1.…”