HR 375: a potential antipsychotic drug that interacts with dopamine D2 receptors and sigma-receptors in the brain.
The potential antipsychotic HR 375 (3-(4-(3-(4-fluorobenzoyl)-propyl-piperazino-1-yl-isoquinolino+ ++-hydrochloride) inhibited [3H]spiperone binding to dopamine D2 receptors and (+)-[3H]SKF-10047 binding to sigma-receptors. The drug was, however, almost inactive in phencyclidine and mu-, kappa- and delta-opioid receptor binding assays. HR 375 inhibited binding of (+)-[3H]SKF-10047 to sigma-sites in a competitive manner. The dissociation constant of (+)-[3H]SKF-10047 binding to sigma-receptors was increased from 62 nM (47-91 nM) to 263 nM (204-370 nM) in the presence of 33 nM HR 375. The number of binding sites (Bmax) was, however, not affected. It is concluded that the pharmacological properties of HR 375, at least in part, may be attributable to its interaction with sigma-receptors.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D006168:Guinea Pigs; D007546:Isoquinolines / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid / Q000187:drug effects*; D017480:Receptors, sigma; D013134:Spiperone / Q000378:metabolism
D014150:Antipsychotic Agents; D007546:Isoquinolines; D010879:Piperazines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011957:Receptors, Opioid; D017480:Receptors, sigma; D013134:Spiperone; C012134:SK&F 10047; C051009:HR 375; D010620:Phenazocine