TYRAMINE ANTAGONISTIC PROPERTIES OF AGN 1135, AN IRREVERSIBLE INHIBITOR OF MONOAMINE OXIDASE TYPE B

Abstract

The effects of the irreversible monoamine oxidase (MAO) inhibitors, AGN 1133, AGN 1135 and (−)‐deprenyl, on tyramine and noradrenaline responses and uptake of [3H]‐metaraminol were investigated in the isolated vas deferens of the rat. Uptake of [3H]‐metaraminol and [3H]‐octopamine was compared in mouse vas deferens. The modification of tyramine and noradrenaline‐induced pressor responses by AGN 1133 and AGN 1135 was examined in anaesthetized rats and cats. AGN 1133 (7.5 × 10−6m) greatly potentiated responses to tyramine in the rat isolated vas deferens. Both AGN 1135 and (−)‐deprenyl inhibited tyramine responses selectively at concentrations above 10−3m (which caused almost complete inhibition of MAO types A and B) but tyramine responses were potentiated on washing out the inhibitors. AGN 1135 (10−4m) and (−)‐deprenyl (10−5m) inhibited [−3H]‐metaraminol uptake by about20% in rat and mouse vas deferens; neither inhibitor affected [−3H]‐octopamine uptake in mouse vas deferens. Desmethylimipramine (10−6m) inhibited amine uptake by more than 70%. AGN 1133 (1.5 mg/kg) potentiated pressor responses to tyramine in rats and cats whereas AGN 1135 (1.5 mg/kg) did not. AGN 1135 possesses tyramine antagonistic activity which is qualitatively similar to that of (−)‐deprenyl but which cannot satisfactorily be explained by inhibition of neuronal or granular amine uptake. 1981 British Pharmacological Society