Reference

Aripiprazole: First of a new class of antipsychotics

Aripiprazole: First of a new class of antipsychotics. Luisi, Andrea F. (University of Rhode Island College of Pharmacy, Kingston, RI, USA). Formulary, 37(11), 575-576, 579-582 (English) 2002 Advanstar Communications, Inc. CODEN: FORMF9. ISSN: 1082-801X. DOCUMENT TYPE: Journal; General Review CA Section: 1 (Pharmacology) A review. Aripiprazole is an investigational atypical antipsychotic that received an approvable status from FDA in Sept. 2002 for the treatment of schizophrenia. The decision on approval could be made as early as the end of this year. Aripiprazole offers a unique mechanism of action as a dopamine system stabilizer. Aripiprazole has been effective in both short-term (4-6 wk) and long-term (26-52 wk) treatment trials. It appears to produce less hyperprolactinemia, wt. gain, and extrapyramidal symptoms than other antipsychotics. Aripiprazole is metabolized via the cytochrome P 450 system; however, no drug interactions are known at this time.Except for chemicals metioned above, 9002-62-4 and 129722-12-9 are also used. .

Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology

Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Shapiro, David A.; Renock, Sean; Arrington, Elaine; Chiodo, Louis A.In this study， 51-61-6 and 129722-12-9 are also used.; Liu, Li-Xin; Sibley, David R.; Roth, Bryan L.; Mailman, Richard ( Department of Biochemistry, Case Western Reserve University Medical School, Cleveland, OH 44106, USA). Neuropsychopharmacology, 28(8), 1400-1411 (English) 2003 Nature Publishing Group. CODEN: NEROEW. ISSN: 0893-133X. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Atypical antipsychotic drugs have revolutionized the treatment of schizophrenia and related disorders. The current clin. approved atypical antipsychotic drugs are characterized by having relatively low affinities for D2-dopamine receptors and relatively high affinities for 5-HT2A serotonin receptors (5-HT, 5-hydroxytryptamine (serotonin)). Aripiprazole (OPC-14597) is a novel atypical antipsychotic drug that is reported to be a high-affinity D2-dopamine receptor partial agonist. We now provide a comprehensive pharmacol. profile of aripiprazole at a large no. of cloned G protein-coupled receptors, transporters, and ion channels. These data reveal a no. of interesting and potentially important mol. targets for which aripiprazole has affinity. Aripiprazole has highest affinity for h5-HT2B-, hD2L-, and hD3-dopamine receptors, but also has significant affinity (5-30 nM) for several other 5-HT receptors (5-HT1A, 5-HT2A, 5-HT7), as well as a1A-adrenergic and hH1-histamine receptors. Aripiprazole has less affinity (30-200 nM) for other G protein-coupled receptors, including the 5-HT1D, 5-HT2C, a1B-, a2A-, a2B-, a2C-, b1-, and b2-adrenergic, and H3-histamine receptors. Functionally, aripiprazole is an inverse agonist at 5-HT2B receptors and displays partial agonist actions at 5-HT2A, 5-HT2C, D3, and D4 receptors. Interestingly, we also discovered that the functional actions of aripiprazole at cloned human D2-dopamine receptors are cell-type selective, and that a range of actions (eg agonism, partial agonism, antagonism) at cloned D2-dopamine receptors are possible depending upon the cell type and function examd. This mixt. of functional actions at D2-dopamine receptors is consistent with the hypothesis proposed by Lawler et al (1999) that aripiprazole has functionally selective' actions. Taken together, our results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of functionally selective' activation of D2 (and possibly D3)-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors-particularly 5-HT receptor subtypes (5-HT1A, 5-HT2A). .