CATECHOLAMINES IN AUTISTIC DISORDER - EFFECTS OF AMISULPRIDE AND BROMOCRIPTINE IN A CONTROLLED CROSSOVER STUDY

The biochemical effects on catecholaminergic systems of the dopamine a ntagonist amisulpride and the dopamine agonist bromocriptine were eval uated in a double-blind, randomized, crossover study in children with autistic disorder. Plasma levels of dopamine, norepinephrine, and epin ephrine; urinary concentrations of homovanillic acid (HVA), vanillylma ndelic acid (VMA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG); and plasma prolactin were measured. At doses of amisulpride and bromo criptine that had the expected opposing effects on plasma prolactin, t he drugs' effects on the catecholaminergic systems were similar. Both agents unexpectedly lowered urinary HVA (total, free, and sulfated) al though only amisulpride decreased the HVA levels significantly. This p aradoxical decrease in HVA levels suggests that both dopamine agonists and antagonists could act on autoreceptors or presynaptic dopaminergi c receptors in the central nervous system. There was no significant ac tion of either drug on plasma epinephrine, urinary VMA, or urinary MHP G, suggesting that neither drug altered norepinephrine or epinephrine systems; however, a weak increase of plasma norepinephrine occurred af ter amisulpride treatment, consistent with effects observed with other neuroleptics. Neither agent altered plasma dopamine, suggesting that peripheral dopamine metabolism was unchanged. The clinical effects of amisulpride and bromocriptine have been reported to be unexpectedly co mplementary. The complementary clinical effects of a dopamine agonist and dopamine antagonist might speculatively be related to their simila r action on dopamine autoreceptors, leading to a correction of the dop aminergic hyperactivity that has been postulated in autistic children.