Action of beta-phenylethylamine and related amines on nigrostriatal dopamine neurotransmission

Abstract

The present paper describes the effect of beta-phenylethylamine and its metabolites phenylethanolamine, tyramine, acetyl-phenylethylamine and phenylacetaldehyde on the dopaminergic nigrostriatal system. The rotational behavioural response to the i.v. injection of these drugs was quantified in animals with a unilateral 6-hydroxydopamine lesion of the nigrostriatal dopamine system. Only beta-phenylethylamine and acetyl-phenylethylamine induced rotations ipsilateral to the side of the brain lesion. None of the compounds under study stimulated contralateral rotations. Acetyl-phenylethylamine was 90% less active than beta-phenylethylamine. After beta-phenylethylamine injection all animals (16/16) showed ipsilateral rotations. The dose-response curve showed that at doses as low as 1.75 mg/kg ipsilateral turns increase, with a dose-related rotational response between 1.75 mg/kg and 11.66 mg/kg, no differences being found at doses between 11.66 and 29.16 mg/kg. Rotations began a few seconds after beta-phenylethylamine injection. The highest response was found 30-60 s after the injection. The duration of the response was dose-related (4 min for the 3.5 mg/kg doses). The inhibition of dopamine-beta-hydroxylase activity with [1-3,5-difluorobenzyl)imidazole-2-thiol (SKF102698) did not modify the rotational response to beta-phenylethylamine. The inhibition of type B monoamine oxidase activity with l-deprenyl induced a slight increase in the ipsilateral rotational response to beta-phenylethylamine. The inhibition of tyrosine hydroxylase activity with alpha-methyl-p-tyrosine decreased the rotational response to beta-phenylethylamine. The dopamine receptor antagonist, haloperidol, completely blocked the ipsilateral rotational response to beta-phenylethylamine. The blocking of dopamine uptake into storage vesicles with reserpine increased the rotational action of beta-phenylethylamine. Taken together, the data suggest that, at low doses, beta-phenylethylamine stimulates the release of dopamine from the cytoplasmic pool and behaves as a dopamine receptor agonist with a very rapid and brief action.