EFFECT OF -METHYL-3,4-DIHYDROXYPHENYLALANINE (METHYLDOPA), RESERPINE AND RELATED AGENTS ON SOME VASCULAR RESPONSES IN THE DOG

¹ Merck Institute for Therapeutic Research, West Point, Pennsylvania

Methyldopa (-methyl-3,4-dihydroxyphenyl-alanine), -methyl-meta-tyrosine and their respective -methyl-dihydroxyphenethylamines were demonstrated to be capable of antagonizing the cardiovascular actions of phenethylamine and amphetamine, but not norepinephrine, after appropriate pretreatment in dogs. In this respect the effects of these agents resembled those obtained with pretreatment with reserpine, syrosingopine and guanethidine. In contrast, these latter agents readily blocked the pressor response that occurs during stimulation of the central end of the vagus nerve whereas the -methyl amino acids and amines were without effect.

The -methyl amino acids produced a decrease in the concentration of catecholamines in the brain stem, heart and spleen after pretreatment, but not the adrenal gland in the pretreated dog. This action, except for the lack of effect on adrenal catecholamines, paralleled that reported for reserpine, syrosingopine and guanethidine in the dog and that reported for the amines derived from the a-methyl amino acids in other species. The ability of the -methyl amino acids and amines to antagonize differentially the vascular effect of the sympathomimetic amines employed may be related to their ability to reduce the catecholamine content of some peripheral tissues. This latter effect, however, was not associated with disruption in transmission over sympathetic pathways since the pressor response occurring during stimulation of the central end of the vagus nerve was not reduced. The possible site and mechanism of action were discussed.

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