Neuroleptic Receptors: Their Characteristics in the Mammalian Central Nervous System and Their Alteration in Human Neuropsychiatric Disorders

3 H-Spiroperidol, a butyrophenone antipsychotic agent, binds specifically and with high affinity to neuroleptic receptors in the 3 corpus striatum and substantia nigra. Scatchard analysis of Hspiroperidol isotherms in the rat striatum revealed a dissociation constant (KQ) of 30 pM and a total receptor density (Bmax) of 430 fmoles/mg protein. In the substantia nigra, the and Bmax values were 42 pM and 41 fmoles/mg protein, respectively. Kinetic analysis of 3 H-spiroperidol binding to rat striatal membranes indicated that binding reached equilibrium by 20 minutes with a rate constant of association 9 -1 -1 (k^) of 2.5 x 10 M min . The rate constant for dissociation (k ) 3 -2 -1 of H-spiroperidol binding was 5.6 x 10 min . The determined from kinetic analysis in the striatum was 22.4 pM. Similarly, the ob3 tained from kinetic analysis for H-spiroperidol binding in the rat 3 substantia nigra was 26 pM. The t . of dissociation for H-spiroJ./ c. peridol binding in both the rat corpus striatum and substantia nigra was 12 minutes and 17 minutes, respectively. A number of dopamine antagonists and agonists effectively in3 hibited H-spiroperidoi binding in the corpus striatum. The rank order (from highest to lowest potency) of various antipsychotic agents in 3 displacing H-spiroperidol binding was spiroperidol > pimozide > (+)butaclamol > haloperidol > fluphenazine > chlorpromazine > clozapine > (,-).-butaclamol. Dopamine analogs were generally more potent than any 3 other neurotransmitter agonists in inhibiting H-spiroperidol. A