Interactions of neuroleptic compounds at alpha 2-adrenergic receptor affinity states in bovine caudate nucleus.

Several recent studies have suggested a connection between neuroleptics and/or dopamine systems, and alpha 2-adrenergic receptors. Competition of a variety of neuroleptics at specific alpha 2-adrenergic binding sites (labeled with [3H]rauwolscine or [3H]p-aminoclonidine) in bovine caudate and cortex was examined. Few of the compounds were potent competitors, with (+)-butaclamol, alpha-flupenthixol, clozapine and pimozide the most potent (IC50 range 100-600 nM), while triflupromazine, mesoridazine, and haloperidol were the least potent (IC50 range 5 000-10 000 nM). These findings indicate that few, if any, of the examined neuroleptics have specific, high-affinity interactions with the multiple affinity states of the alpha 2-adrenergic receptor.