An investigation of alpha-methyl amino-acids and their derivatives on isolated tissue preparations

Abstract

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.