Pharmacological studies on supersensitization. IX. Non-specific supersensitivity of vas deferens of guinea pig induced by tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine.
Effects of tripelennamine, N,N-dimethyl-N',N'-dibenzylethylenediamine (DBED) and N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine (DBPD) on the isotonic contractions of isolated vas deferens of guinea pig were examined. These ethylenediamines, except DBPD, induced slight but significant increase in sensitivity of vas deferens to K+. Tripelennamine induced dose-dependent potentiation to epinephrine and norepinephrine, but tripelennamine-induced augmentation of acetylcholine-contractions was weak and dose-independent. DBED potentiated both catecholamines and acetylcholine in a dose-dependent way and in the same degree. The degree of DBPD-induced augmentation of epinephrine- and norepinephrine-induced contractions was dose-independent and much weaker than that of acetylcholine-contractions. Tripelennamine and DBED did not affect the contractile response to tyramine, while DBPD potentiated the contractile response to tyramine. These results suggest the following possibilities: 1) tripelennamine affects both amine uptake mechanism and beyond receptor mechanism of contractile processes and induced supersensitivity of various stimulants. 2) DBED affects mainly beyond receptor mechanism of contractile processes and augments the contractile responses to various stimulants. 3) The mechanism of DBPD-induced supersensitivity remained obscure, but the inhibition of the metabolic degradation of stimulants was proposed as one of the possible mechanism of supersensitization.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D005029:Ethylenediamines / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D014309:Tripelennamine / Q000494:pharmacology*; D014439:Tyramine / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects
D003959:Diamines; D005029:Ethylenediamines; D014309:Tripelennamine; C037337:N,N-dimethyl-N',N'-dibenzylethylenediamine; C037338:N,N-dibenzyl-N',N'-dimethyl-1,2-propanediamine; D012110:Reserpine; D003042:Cocaine; D000109:Acetylcholine; D011188:Potassium; D014439:Tyramine; D004837:Epinephrine