title: Initial human experience with MK-462 (rizatriptan): a novel 5-HT1D agonist.
abstract: 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.
authors.affiliation: Merck Research Laboratories, Rahway, New Jersey, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Sciberras
authors.forename: W J
authors.initials: WJ
authors.lastname: Polvino
authors.forename: B J
authors.initials: BJ
authors.lastname: Gertz
authors.forename: H
authors.initials: H
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Stepanavage
authors.forename: J
authors.initials: J
authors.lastname: Wittreich
authors.forename: T
authors.initials: T
authors.lastname: Olah
authors.forename: M
authors.initials: M
authors.lastname: Edwards
authors.forename: T
authors.initials: T
authors.lastname: Mant
mesh_terms: 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
chemical_list: D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D018170:Sumatriptan