Relationship between the ability of some neuroleptics to enhance striatal [3H]dopamine release and their lipophilicity.
The ability of micromolar concentrations (100 microM) of some neuroleptics to enhance release of [3H]dopamine from rat striatum was studied. All the neuroleptics tested potentiated [3H]dopamine release, the most potent being chlorpromazine, prochlorperazine and fluphenazine and the least potent being sulpiride and metoclopramide. Apomorphine did not reverse the effects of fluphenazine and the stereo-isomers of flupenthixol were almost equipotent. These results indicated a direct, non-receptor, mediated mechanism. The lipophilicity of the neuroleptics, determined by reversed-phase TLC, showed a good correlation with their ability to enhance dopamine release. It is concluded that the lipophilicity of these drugs is partly responsible for the enhanced release of dopamine and may be clinically important following chronic administration of neuroleptics.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005476:Fluphenazine / Q000494:pharmacology; D066298:In Vitro Techniques; D008055:Lipids; D008297:Male; D010640:Phenothiazines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D014316:Tritium
D014150:Antipsychotic Agents; D008055:Lipids; D010640:Phenothiazines; D014316:Tritium; D011188:Potassium; D005476:Fluphenazine; D004298:Dopamine