Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro

Using radioligand binding techniques, we determined the equilibrium dissociation constants (K_D's) for a series of neuroleptics at the dopamine (D-2), muscarinic, histamine H₁, α₁- and α₂-adrenergic receptors of normal human brain tissue obtained at autopsy. Seventeen different compounds were studied at the D-2 receptor and 15 compounds at the remaining receptors. At the D-2 receptor of caudate nucleus, spiperone was the most potent compound (K_D = 0.16 nM); clozapine the least potent (K_D = 180 nM). The K_D's for six compounds at the D-2 receptor of nucleus accumbens were not significantly different from their respective K_D's in the caudate nucleus. The most potent and least potent compounds at the other receptors were clozapine and molindone at the muscarinic receptor, mesoridazine and molindone at the H₁ receptor, spiperone and molindone at the α₁-receptor, and clozapine and haloperidol at the α₂-receptor, respectively.