3-Methoxytyramine and normetanephrine as indicators of dopamine and noradrenaline release in mouse brain in vivo.

Intraperitoneal administration of pargyline HCl induced a dose-dependent accumulation of 3-methoxytyramine and normetanephrine in mouse brain in vivo. As judged by the decrease of 5-hydroxyindole acetic acid levels a dose of 200 mg/kg of pargyline appeared to inhibit monoamine oxidase completely. This dose led to an approximately linear accumulation of 3-methoxytyramine and normetanephrine during the first 3 hours. gamma-Butyrolactone, 750 mg/kg i.p. reduced the accumulation of 3-methoxytyramine despite a marked increase of dopamine. (+)-Amphetamine stimulated 3-methoxytyramine as well as normetanephrine accumulation at doses of 3 and 10 mg/kg i.p. In line with the concept of receptor-mediated negative feedback control of catecholaminergic transmission the dopamine receptor agonists apomorphine, 0.3 mg/kg i.p., lisuride, 0.05--0.3 mg/kg i.p., and bromocriptine, 10 mg/kg i.p., decrease 3-methoxytyramine formation while the dopamine receptor blocking agent haloperidol, 1 mg/kg i.p., led to a 3-fold increase. The alpha-adrenoceptor agonist clonidine, 0.1 mg/kg i.p., reduced the formation of normetanephrine and the alpha-adrenoceptor antagonists yohimbine, 10 mg per kg i.p., phenoxybenzamine, 20 mg/kg i.p., and mianserine, 50 mg/kg i.p., stimulated normetanephrine accumulation 1.5- to 4-fold. 3-Methoxytyramine and normetanephrine accumulating after inhibition of monoamine oxidase appear to be reliable indicators of dopamine and noradrenaline release and metabolism.