Methoxyphenamine inhibits histamine-induced bronchoconstriction in anaesthetized guinea-pigs and histamine-induced contractions of guinea-pig ileum in vitro.
Measurements were made of the effects of methoxyphenamine hydrochloride on histamine-, acetylcholine- and U46619-induced bronchoconstriction in pentobarbitone-anaesthetized guinea-pigs, and on histamine- and acetylcholine-induced contractions of guinea-pig ileum in vitro. Methoxyphenamine (20 mg/kg, i.v.) did not affect bronchoconstriction induced by acetylcholine or the thromboxane A2-mimetic U46619. However, it produced a parallel rightward shift [2.94-(1.79, 4.41) fold, 95% confidence limits in parentheses] of the curve relating bronchoconstrictor responses to log-dose of histamine at a total dose of 13 mg/kg, i.v., which was not significantly different from the shift [3.30-(1.93, 5.56) fold] produced by 3 micrograms/kg, i.v., of the histamine antagonist mepyramine maleate. Histamine-induced contractions of the isolated guinea-pig ileum were antagonized by methoxyphenamine (10(-5) to 10(-3) M). The histamine log-concentration-response curve was shifted to the right in a parallel manner by methoxyphenamine (10(-5) to 10(-4) M), without depression of maximum responses. However, at higher concentrations, maximum responses were reduced. The slope of the Schild plot was significantly different from -1. The degree of the rightward shift of the concentration-response curves to histamine, produced by 10(-5) M of methoxyphenamine [3.90-(2.83, 4.97) fold], was not significantly different from that produced by 3 x 10(-9) M of mepyramine [4.60-(2.86, 6.52) fold]. Methoxyphenamine, at concentrations of 10(-5) to 3 x 10(-4) M, had no significant effect on responses of guinea-pig ilea to acetylcholine (10(-9) to 10(-5) M). These results indicate that methoxyphenamine antagonizes the effects of histamine both in vivo and in vitro. In vitro studies indicate a noncompetitive antagonism.
Callaway
J K
JK
Department of Pharmacology, Manash University, Clayton, Victoria, Australia.
King
R G
RG
Boura
A L
AL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001980:Bronchi / Q000187:drug effects*; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D006633:Histamine Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D008694:Methamphetamine; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D006632:Histamine; D011738:Pyrilamine; C005157:methoxyphenamine; D000109:Acetylcholine