Inhibitors of phenylethanolamine-N-methyltransferase. 2. Comparison of nonaromatic analogs of phenylethanolamines, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline (SKF-64139) and 2,3-dichloro-alpha-methylbenzylamine: effects on rat brain and adrenal catecholamine content and blood pressure

Abstract

Intraperitoneal injections of the phenylethanolamine N-methyltransferase inhibitors 2-cyclohexyl-2-hydroxyethylamine, 1-aminomethylcycloundecanol, 7,8-dichloro-1,2,3,4-tetrahydroisoquinoline and 2,3-dichloro-alpha-methylbenzylamine all lowered blood pressures in spontaneously hypertensive rats. The drugs did not affect the blood pressures of age-paired normotensive Wistar Kyoto rats or did the drugs alter the heart rates of either animal group. All of the phenylethanolamine N-methyltransferase inhibitors tested lowered hypothalamic epinephrine content which in spontaneously hypertensive rats could be correlated with the reduction in blood pressure. These data support the hypothesis that central nervous system epinephrine may play an important role in the regulation of blood pressure and in the genesis and/or maintenance of hypertension. The results also suggest the hypothesis that the blood pressure lowering effects of phenylethanolamine N-methyltransferase inhibitors may be mediated by their effects on hypothalamic epinephrine content.