Effect of neuroleptics on the disappearance rate of [14C] labelled catecholamines formed from [14C]tyrosine in mouse brain

Abstract

Abstract The accumulation and disappearance of [14C] labelled dopamine and noradrenaline formed from [14C]tyrosine in mouse brain has been investigated. After reaching peak concentrations the [14C]dopamine and noradrenaline concentration declined exponentially with half-lives of 2·5 and 6·7 h respectively. The effect of some known neuroleptics belonging to different chemical groups as well as of a new neuroleptic compound, Lu 10–022 [2-trifluormethyl-6-fluoro-9-(3-(4-(2-hydroxyethyl) piperazin-l-yl)propyl) thioxanthen], on the disappearance rate of [14C]catecholamines between 1·5 and 3 h after administration of [14C]tyrosine was compared. All neuroleptics tested, except clozapine, increased the disappearance rate of [14C]dopamine in a dose-dependent manner at the lower dose intervals. However, above a certain dose the disappearance rate was not elevated further. Halo-peridol, fluphenazine and Lu 10–022 increased the disappearance of [14C]dopamine more strongly than the rest of the neuroleptics. The disappearance rate of [14C]noradrenaline was also increased by all the neuroleptics, except clopenthixol, although the change was less than for [14C] dopamine disappearance, resulting in a rather poor dose-response relation. Pimozide and Lu 10–022 influenced the [14C] noradrenaline disappearance less than the other neuroleptics. The hypothermic effect caused by the neuroleptics was not related to the change in the disappearance rate of the catecholamines.