title: MK-208, a novel histamine H2-receptor inhibitor with prolonged antisecretory effect.
abstract: MK-208 is a guanidinothiazole derivative reported to be a potent H2 blocker devoid of antiandrogenic activity. Its potency and duration of action, in inhibiting pentagastrin-stimulated gastric secretion in man, was evaluated in this double-blind, five-way cross-over trial. Ten healthy male volunteers received single oral doses of placebo, cimetidine 300 mg, and MK-208 5, 10, and 20 mg. A continuous intravenous infusion of pentagastrin (1 microgram/kg/hr) was given 2-4 and 5-7 hr after each oral dose. Gastric contents were continuously aspirated and volumes and acid content determined every 30 min. Plasma levels for MK-208 and cimetidine were monitored over the 7 hr of the study. Cimetidine and all doses of MK-208 significantly inhibited gastric acid secretion in the initial 2-4 hr; however, 10- and 20-mg doses of MK-208 were significantly more potent than cimetidine. In the 5- to 7-hr period, cimetidine 300 mg was not different from placebo, while MK-208 in all doses studied continued to significantly suppress gastric secretion. Plasma levels for MK-208 showed dose-related increments. The results suggest that: (1) MK-208 is a potent inhibitor of gastric secretion in man, in a dose-related fashion at the doses tested; (2) under the study conditions, 5 mg MK-208 was equipotent to 300 mg cimetidine but with greater duration of action, extending at least 7 hr; and (3) these data suggest a future role for this new agent in therapy for acid-peptic disease in man.
authors.forename: R W
authors.initials: RW
authors.lastname: McCallum
authors.forename: A N
authors.initials: AN
authors.lastname: Chremos
authors.forename: B
authors.initials: B
authors.lastname: Kuljian
authors.forename: M A
authors.initials: MA
authors.lastname: Tupy-Visich
authors.forename: P B
authors.initials: PB
authors.lastname: Huber
mesh_terms: D000328:Adult; D002927:Cimetidine / Q000378:metabolism / Q000494:pharmacology; D015738:Famotidine; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D010418:Pentagastrin; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D006635:Histamine H2 Antagonists; D013844:Thiazoles; D015738:Famotidine; D002927:Cimetidine; D010418:Pentagastrin