The use of thioproperazine, a phenothiazine derivative, as a ligand for neuroleptic receptors—I: In vitro studies

Abstract

The use of [ 3H]thioproperazine (a neuroleptic of the phenothiazine family) as a ligand for neuroleptic receptors has been studied in vitro in various brain regions of the rat. Specific thioproperazine binding has been observed in two regions rich in dopamine terminals: striatum and nucleus accumbens. No specific binding was observed in frontal cortex and hippocampus. Thioproperazine binds with high affinity ( K d = 0.30 nM) to rat microsomal striatal fraction. In this fraction the number of binding sites (1.47 pmoles/mg protein) is rather similar to that found with haloperidol and spiperone, two neuroleptics of the butyrophenone type. Subcellular distribution of thioproperazine binding reveals a pattern similar to that of 5'-nucleotidase, a plasma membrane marker. This indicates that the receptor sites of [ 3H]thioproperazine are associated with membrane-like structures. Inhibition studies indicate that all neuroleptic compounds, belonging to different chemical families, are capable of displacing thioproperazine from its binding sites. The most potent drugs are spiperone, thioproperazine and pipotiazine. Dopamine and the two dopamine agonists, apomorphine and bromocryptine, present affinity for thioproperazine binding sites. It is concluded that thioproperazine, a phenothiazine neuroleptic, can be used, like the butyrophenone derivatives haloperidol and spiperone, as a ligand for studying neuroleptic receptors.