Spiperone: A ligand of choice for neuroleptic receptors

It is concluded that spiperone is a more suitable ligand than haloperidol for studying the neuroleptic receptors.

Abstract

A binding assay for neuroleptic receptors has been developed with spiperone as the labelled ligand. As compared to haloperidol, spiperone showed a 2-times higher ratio of specific versus aspecific binding, a 10-fold greater association constant and a slower dissociation of the receptor ligand complex. The receptor sites labelled by spiperone appeared to be for a great deal similar to those of haloperidol, however certain differences were apparent; the number of receptor sites per gram of tissue was found to be higher for the former; spiperone showed a biphasic receptor ligand dissociation curve which was not observed for haloperidol; also a slight difference in physical stability between spiperone and haloperidol binding sites was noted. Inhibition studies using antagonists and agonists in comparison with the pharmacological profile of the compounds showed that the receptor sites labelled by both ligands are mainly of dopaminergic nature, but also a serotonergic and to a minor extent a noradrenergic component should be involved. Within the striatum haloperidol binding sites seemed to be relatively more related to dopaminergic sites whilst the spiperone binding sites appeared to comprise a higher serotonergic component. It is concluded that spiperone is a more suitable ligand than haloperidol for studying the neuroleptic receptors. The use of different labelled ligands provided evidence for the heterogeneity of the neuroleptic binding sites in the striatum.