Antipsychotic drug action: antagonism, inverse agonism or partial agonism.
The positive, psychotic symptoms of schizophrenia can be treated by antipsychotic drugs and it has been assumed that these are antagonists at the D(2) and D(3) dopamine receptors in the brain. Recently, the D(2)/D(3) partial agonist aripiprazole has been introduced as an antipsychotic drug. It has also been realized that, using in vitro assays, the other antipsychotic drugs are in fact inverse agonists at D(2)/D(3) dopamine receptors. This raises questions about how these disparate drugs can achieve a similar clinical outcome. In this review, I shall consider the efficacies of these drugs in signalling assays and how these efficacies might affect treatment outcomes. It seems that the treatment outcome might depend on the overall level of cell stimulation, which is in turn dependent on the level of residual dopamine and the efficacy of the drug in signalling assays.
Strange
Philip G
PG
School of Pharmacy, PO Box 228, University of Reading, Whiteknights, Reading RG6 6AJ, UK. p.g.strange@reading.ac.uk
D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D054314:Drug Inverse Agonism; D006801:Humans; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3 / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D000068180:Aripiprazole