Effects of a single administration of clozapine on mouse brain catecholamines.

Abstract

Abstract The effects of clozapine on the accumulation and disappearance of 14C‐labelled catecholamines formed from 14C‐tyrosine, and on the endogenous levels of catecholamines have been studied in mouse brain. Rather low doses of clozapine increased noradrenaline accumulation and disappearance (from 2.5 and 0.16 mg/kg, respectively), whereas dopamine accumulation was only increased from 10 mg/kg and disappearance after 80 mg/kg. However, in the dosage interval of 1.25 to 5 mg/kg dopamine disappearance was decreased. Endogenous noradrenaline levels were decreased from 10 mg/kg in contrast to the dopamine levels which remained unchanged, except in the dosage interval 2.5 to 10 mg/kg, where they were elevated, at the same time at which dopamine disappearance was decreased. It is concluded that clozapine differs biochemically from the typical neuroleptics by changing the metabolism of noradrenaline in doses much lower than those influencing dopamine metabolism. It is suggested that this property together with the ability of clozapine to decrease dopamine disappearance in a certain dose range, could contribute to the unique psychopharmacological action of clozapine.