Blockade of hippocampal dopamine (DA) receptors: a tool for antipsychotics with low extrapyramidal side effects.
1. 32 neuroleptics (NL) and a Ciba-Geigy antipsychotic (savoxepine, CGP 19 486 A) were tested on adult male rats and mice. 2. Interaction with D2 DA receptors was assessed using in vivo (3H)spiperone (SPI) binding in rat hippocampus and striatum. 3. Antipsychotic efficacy of NL was checked by their ability to antagonize apomorphine-induced climbing behavior in mice. 4. We found a good correlation between blockade of DA receptors in hippocampus and antagonism of climbing with both classical and atypical NL. 5. No correlation was found between blockade of DA receptors in striatum and climbing with the atypical NL. 6. It is suggested that NL exerting preferential blockade of hippocampal as compared to striatal DA receptors may show a better dissociation between antipsychotic efficacy and induction of extrapyramidal side effects (EPS) in the clinic. The antipsychotic agent savoxepine, displayed such a favourable profile of action.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005116:Extrapyramidal Tracts / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D013134:Spiperone; D001058:Apomorphine