Evidence that deprenyl,a type B monoamine oxidase inhibitor,is an indirectly acting sympathomimetic amine

Various doses of l-deprenyl were tested for their abilities to increase blood pressure or heart rate in animals pretreated with a ganglionic blocking agent. The use of a ganglionic blocker (chlorisondamine) ensured that deprenyl-induced responses were mediated by the peripheral autonomic nervous system, and that these responses were not influenced by the central nervous system. It was found that l-deprenyl had a modest ability to increase blood pressure and a marked ability to increase heart rate. The ability of l-deprenyl to increase heart rate was diminished or abolished by propranolol, reserpine, and chemical sympathectomy (6-hydroxydopamine). Deprenyl-induced responses were negligibly affected by adrenalectomy. These data suggest that l-deprenyl is an indirectly acting sympathomimetic amine whose responses are mediated by norepinephrine in postganglionic sympathetic neurons. An additional finding was that desmethylimipramine, a known blocker of the norepinephrine pump, antagonized the effects of l-deprenyl. This finding suggests that l-deprenyl enters sympathetic neurons via the membrane pump. The ability of l-deprenyl to enter sympathetic neurons and evoke release of endogenous amines was not accompanied by a significant loss of tissue (heart) norepinephrine.