The Influence of Chlorpromazine on the Metabolism of 5-hydroxytryptamine in the Mouse.

The aim of the present experiments was to clarify the influence of chlorpromazine on 5-hydroxytryptamine (5HT) in mouse brain. It was shown earlier (Bartlet, 1960) that the injection of iproniazid into mice produced an accumulation of cerebral 5HT, and that the rate of accumulation of the amine was reduced by chlorpromazine. It was suggested that chlorpromazine reduced the rate of formation of cerebral 5HT, so that, when monoamine oxidase was inhibited, chlorpromazine reduced the accumulation of unmetabolized amine. Ehringer, Hornykiewicz & Lechner (1960) and Gey & Pletscher (1961) confirmed that chlorpromazine reduced the accumulation of cerebral 5HT produced by inhibitors of monoamine oxidase, and suggested that chlorpromazine impaired the storage of cerebral 5HT, so that, when monoamine oxidase was inhibited, 5HT diffused out of the brain as the cells could no longer store the amine. More recently, Morpurgo (1962) reported that the influence of chlorpromazine on 5HT metabolism was an outcome of hypothermia. A mechanism controlling the metabolism or storage of 5HT may well be temperaturedependent; nevertheless, according to Gey & Pletscher (1964), the influence of chlorpromazine on monoamine metabolism was not solely dependent upon hypothermia. The results of the experiments described in the present paper are in accord with the concept of a reduction in metabolism of brain 5HT after chlorpromazine, but do not support the hypothesis that the effect of chlorpromazine on 5HT is primarily an impairment of storage in the tissues. The present experiments also confirm that the influence of chlorpromazine on 5HT metabolism is an outcome of hypothermia.