[Pharmacological studies on supersensitization. V. Augmentation of pressor response to catecholamine induced by N, N-dimethylethylenediamines (author's transl)].
Effects of N,N-dimethylethylenediamines on epinephrine-induced pressor response in pentobarbital-anesthetized rats were examined and 3 out of 12 compounds, i.e., tripelennamine, N,N-dibenzyl-N', N'-dimethylethylenediamine (I) and N1, N1-dibenzyl-N2, N2-dimethyl-1,2-propanediamine (II), were found to be more potent as potentiators to epinephrine. In pithed rats, tripelennamine, I, II and cocaine also augmented pressor response induced by epinephrine. In pentobarbital-anesthetized rats or in perfused hind paw of rats, the potentiation induced by cocaine and tripelennamine was more marked to norepinephrine than to epinephrine, but an inverse relation between norepinephrine and epinephrine was observed in the potentiation by I and II. In pentobarbital-anesthetized rats, tyramine-induced pressor responses were decreased or abolished by cocaine and tripelennamine, but these responses were increased by I and II. In pentobarbital-anesthetized rats, isoproterenol-, acetylcholine- and histamine-induced depressor responses were not influenced by cocaine, tripelennamine, I and II. Sensitivity of reserpinized rats to epinephrine was increased about eight times that seen in pentobarbital-anesthetized rats. In reserpinized rats, epinephrine-induced pressor responses were slightly increased by cocaine, tripelennamine and II, but these potentiations were not dose-dependent. These results indicate that one of the sites of action of cocaine, tripelennamine, I and II is localized in the peripheral portion of cardiovascular system. The principal mode of action of cocaine and tripelennamine appears to be the inhibition of amine-uptake mechanism at sympathetic nerve endings. The mode of action of I and II is apparently different from the actions of cocaine and tripelennamine.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D004357:Drug Synergism; D004837:Epinephrine / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D008297:Male; D051379:Mice; D014309:Tripelennamine / Q000494:pharmacology
D005029:Ethylenediamines; D014309:Tripelennamine; D003042:Cocaine; D004837:Epinephrine