An investigation of alpha-methyl amino-acids and their derivatives on isolated tissue preparations.
1. The ability of alpha-methyl amino-acids and their corresponding amines to restore the sympathomimetic actions of tyramine, and the uptake of the amino-acids and the amines, were studied in isolated tissue preparations obtained from reserpine pretreated animals.2. Tyramine relaxed isolated rat ileum preparations from non-reserpinized rats but not from reserpine treated animals. alpha-Methyldopa, alpha-methylnoradrenaline and lower concentrations of metaraminol restored the responses of reserpinized preparations. alpha-Methyldopamine, alpha-methyl-m-tyrosine, alpha-methyl-p-tyrosine and higher concentrations of metaraminol did not do so. The restoring effect of alpha-methyldopa was blocked by disulphiram. alpha-Methyl-p-tyrosine or alpha-methyl-m-tyrosine blocked the restoring action of alpha-methyldopa but not of alpha-methylnoradrenaline. Cocaine blocked the restoration of responses to tyramine by alpha-methylnoradrenaline but not by alpha-methyldopa. alpha-Methyldopa and alpha-methylnoradrenaline failed to restore responses to tyramine in the presence of sodium-free Tyrode solution.3. Tyramine increased the perfusion pressure in isolated rabbit ear preparations obtained from non-reserpinized animals but was very much less active in preparations obtained from reserpine treated animals. alpha-Methyldopa, alpha-methyl-m-tyrosine, alpha-methylnoradrenaline, alpha-methyl-p-tyrosine and metaraminol restored the effects of tyramine. alpha-Methyldopamine did not do so. The restoring effect of alpha-methyldopa and alpha-methyl-m-tyrosine was blocked by disulfiram. alpha-Methyl-p-tyrosine blocked the restoring effect of alpha-methyl-m-tyrosine.4. Tyramine produced positive inotropic effects in isolated rabbit heart preparations. This was either reduced or absent in preparations obtained from reserpine pretreated animals. alpha-Methyldopa, alpha-methylnoradrenaline, alpha-methyl-m-tyrosine and metaraminol restored the responses to tyramine. alpha-Methyldopamine and alpha-methyl-p-tyrosine did not do so.
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004221:Disulfiram / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004431:Ear, External / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D008680:Metaraminol / Q000494:pharmacology; D008750:Methyldopa / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008781:Methyltyrosines / Q000494:pharmacology; D009647:Normetanephrine / Q000494:pharmacology; D010477:Perfusion; D011817:Rabbits; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012964:Sodium; D014439:Tyramine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000596:Amino Acids; D008781:Methyltyrosines; D009647:Normetanephrine; D008750:Methyldopa; D008680:Metaraminol; D012110:Reserpine; D012964:Sodium; D003042:Cocaine; D004221:Disulfiram; D004298:Dopamine; D014439:Tyramine