Effect of neuroleptic drugs on central catecholamine turnover assessed using tyrosineand dopamine-β-hydroxylase inhibitors

Abstract

The effects of some neuroleptic drugs on the noradrenaline turnover in the rat brain and spinal cord were studied biochemically and histochemically with the help of a new inhibitor of the enzyme dopamine-β-hydroxylase, bis(4-methyl-1-homopiperazinyl-thiocarbonyl) disulphide; (FLA-63). Haloperidol (1 mg/kg, i.p.), chlorpromazine (5–10 mg/kg, i.p.), pimozide (1–5 mg/kg, i.p.) and fluspirilene (1–5 mg/kg, i.p.) produced an acceleration of the noradrenaline disappearance induced by FLA-63. Clothiapine (1 mg/kg, i.p.) was ineffective. The lowering of brain dopamine after treatment with α-methyltyrosine methylester (H44/68) was markedly enhanced by haloperidol (5 mg/kg, i.p.) and slightly so by chlorpromazine (5 mg/kg, i.p.), whereas both drugs simultaneously caused a significant increase in the noradrenaline loss. Thus, the same results were obtained with dopamine-β-hydroxylase and tyrosine-hydroxylase inhibition on the influence of neuroleptic drugs on the noradrenaline turnover. The acceleration seen after haloperidol and chlorpromazine, but not after pimozide and fluspirilene, could be due to a compensatory activation of noradrenaline neurons produced by a noradrenaline receptor blockade.