Regulation in the central norepinephrine neurotransmission induced in vivo by alpha adrenoceptor active drugs.

The level of the two major norepinephrine metabolites, 3-methoxy-4-hydroxyphenylglycol (MOPEG) and 3,4-dihydroxyphenylglycol (DOPEG), was estimated in the central nervous system of rats to study receptor-mediated regulation of release in vivo as reflected in biochemical changes. The norepinephrine receptor stimulating drug clonidine (0.02-0.5 mg/kg) decreased the level of endogenous total MOPEG. The accumulation of 3H-MOPEG and 3H-DOPEG was decreased by clonidine (0.5 mg/kg) regardless of whether 3H-tyrosine or 3H-dopamine was used as precursor of 3H-norepinephrine. In contrast to clonidine, the two alpha adrenoceptor blocking drugs, phenoxybenzamine (20 mg/kg) and aceperone (20 mg/kg), induced an increase in endogenous total MOPEG and also an increase in 3H-MOPEG and 3H-DOPEG regardless of the precursor used. These results indicate that clonidine decreases the release of norepinephrine in vivo and that phenoxybenzamine and aceperone increase the release of norepinephrine. Clonidine inhibited completely the effect of phenoxy benzamine or aceperone on endogenous MOPEG. On the contrary, it was not possible to block completely the effect of small doses of clonidine by pretreatment with either phenoxybenzamine, yohimbine (2 mg/kg) or a high dose of aceperone. These results indicate that clonidine may act on a different target than the alpha adrenoceptor blocking drugs. In vitro experiments with occipital cortex synaptosomes did not indicate a direct effect of clonidine on tyrosine hydroxylation in noradrenergic nerve terminals.