Initial human experience with MK-462 (rizatriptan): a novel 5-HT1D agonist.
OBJECTIVE
We evaluated the pharmacokinetics and pharmacodynamics of oral MK-462 in comparison with oral sumatriptan in healthy male volunteers.


METHODS
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 tmax 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 5-10 mmHg in systolic and diastolic blood pressures without effect on heart rate; the changes occurred sooner following MK-462, consistent with more rapid absorption. Both MK-462 and sumatriptan provoked mild increases in serum growth hormone without any effect on serum prolactin concentrations. The most commonly reported symptom following MK-462 was drowsiness.


CONCLUSIONS
These results indicate that the novel 5-HT1D agonist, MK-462, is rapidly absorbed following oral administration and warrants further investigation of its utility in the treatment of acute migraine.
Sciberras
D G
DG
Merck Research Laboratories, Rahway, New Jersey, USA.
Polvino
W J
WJ
Gertz
B J
BJ
Cheng
H
H
Stepanavage
M
M
Wittreich
J
J
Olah
T
T
Edwards
M
M
Mant
T
T
D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000493:pharmacokinetics*; D018170:Sumatriptan / Q000493:pharmacokinetics; D014230:Triazoles / Q000009:adverse effects / Q000493:pharmacokinetics*; D014363:Tryptamines
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D018170:Sumatriptan