FORMATION OF A “FALSE ” ADRENERGIC TRANSMITTER IN CATS PRETREATED WITH 4-METHOXY-3,5-DIHY- DROXYPHENYLALANINE AND ITS EFFECTS ON POSTGANGLIONIC SYMPA- THETIC TRANSMISSION

ABSTRAcT THOENEN, H., W. HAEFELY, G. HAEUSLER AND A. HTJERLIMANN: Formation of a “false” adrenergic transmitter in cats pretreated with 4-methoxy-3,5-dihydroxyphenylalanine and its effects on postganglionic sympathetic transmission. J. Pharmacol. Exp. Therap. 162: 70-79, 1968. Pretreatment of cats with (50 mg/kg p.o. 28, 20 and 4 hr before sacrifice) 4-methoxy-3,5-dihydroxyphenylalanine resulted in a marked depletion of norepinephrine in sympathetically innervated organs (heart, 8.3%; spleen, 72%; iris, 17.3%; and nictitating membrane, 192 % of controls). The response to sympathetic nerve stimulation was dimin-ished in the heart, the nictitating membrane and the isolated perfused spleen in which both contractile response and norepinephrine output was greatly reduced. The effect of i.v. in-jected norepinephrine on blood pressure and nictitating membrane did not differ signifi-cantly from that on untreated controls. The chromatographic analysis of the amines present in spleen and heart after administration of 4-methoxy-3,5-dihydroxyphenylalanine revealed the accumulation of 4-methoxy-3,5-dihydroxyphenethylamine, which was liberated as a false transmitter by sympathetic nerve stimulation. The expected p-hydroxylated metabolit