Receptor-binding profiles of neuroleptics

Abstract

Dopamine-receptor blockade seems to be a prominent effect of neuroleptics. Blockade of other receptors might, however, contribute to the therapeutic effect. A series of neuroleptics have been tested for affinity to DA D-1 and D-2 receptors, serotonin receptors (S2), alpha-adrenoceptors (alpha 1), histamine receptors (H1), and muscarinic cholinergic receptors. According to the affinity to DA D-1 and D-2 receptors, neuroleptics can be divided into different groups. Thioxanthenes have affinity for both D-1 and D-2 receptors; phenothiazines have affinity for D-2 receptors and considerably lower affinity for D-1 receptors; and butyrophenones, diphenylbutylpiperidines, and benzamides have affinity only for D-2 receptors. Concerning affinity to other receptors the only consistent finding is affinity for S2 receptors. The clinical significance of these findings is speculative. In several behavioral tests the D-1/D-2 classification is also observed, and it is suggested that D-1-receptor activation is responsible for dyskinesia, and that thioxanthenes - due to their D-1 receptor blocking effect-induce less dyskinesia than other neuroleptics.