USE OF [H-3] CLOZAPINE AS A LIGAND OF THE DOPAMINE D-4 RECEPTOR SUBTYPE IN PERIPHERAL-TISSUES

1 Molecular biology studies have documented the presence of peripheral dopamine D-4 receptors. This site has not been characterized yet with classical radioligand binding assay techniques because of the lack of selective radioligands.2 The atypical neuroleptic clozapine labelled with tritium ([H-3]-clozapine) has been proposed and sold as a radioli gand for brain dopamine D-4 receptors. However, the selectivity of [H- 3]-clozapine for D-4 receptor subtypes, and its specificity for brain dopamine receptors, have been questioned. 3 In this study dopamine D-4 receptors were assayed in peripheral organs known to express them, su ch as rat atria and kidney, by using a radioligand binding assay techn ique with [H-3]-clozapine as the radioligand. Parallel experiments wer e performed using Chinese hamster ovary (CHO) cells transfected with t he D-4 receptor clone (variant D-4.2) 4 [H-3]-Clozapine was bound to s ections of rat atria and kidney. After appropriate blockade of sites o ther than dopamine receptors to which it can bind (i.e. muscarinic cho linergic, serotonergic and alpha-adrenergic receptors), the radioligan d was bound to a site displaying a pharmacological profile similar to that expressed by CHO cells transfected with the D-4 receptor. 5 The a bove findings indicate that with appropriate protocols, [H-3]-clozapin e may represent a radioligand for peripheral dopamine D-4 receptors.