Further evidence that 3H-cis(Z)flupenthixol binds to the adenylate cyclase-associated dopamine receptor (D-1) in rat corpus striatum

Abstract

The proposal that ³H-cis(Z)flupenthixol (³H-FPT) preferentially binds to striatal dopamine receptors associated with adenylate cyclase activity (D-1), distinct from dopamine receptors to which ³H-haloperidol (³H-hal) binds (D-2), has been investigated further. The dopamine agonists bromocriptine and ergotamine were 60-times more potent as displacers of ³H-hal than ³H-FPT binding. Other dopamine agonists (ergometrine, dopamine, apomorphine, 2-amino-6,7-dihydroxy-tetralin (ADTN), and ergocornine) also shared this profile, although a smaller ratio was found for these compounds. Substituted benzamides (clebopride > sultopride > sulpiride > metoclorpramide > tiapride) displace ³H-hal but have only a very slight displacing effect towards ³H-FPT, and did not inhibit dopamine-stimulated adenylate cyclase activity. The same pattern is shared by oxiperomide and molindone. Together, these results support the idea that ³H-FPT labels another class of dopamine receptors than does ³H-hal, and that the former class most likely is associated with adenylate cyclase.