2719 Aripiprazole Aripiprazole is an atypical antipsychotic medication used for the treatment of schizophrenia. It has also recently received FDA approval for the treatment of acute manic and mixed episodes associated with bipolar disorder. Aripiprazole appears to mediate its antipsychotic effects primarily by partial agonism at the D2 receptor. In addition to partial agonist activity at the D2 receptor, aripiprazole is also a partial agonist at the 5-HT1A receptor, and like the other atypical antipsychotics, aripiprazole displays an antagonist profile at the 5-HT2A receptor. Aripiprazole has moderate affinity for histamine and alpha adrenergic receptors, and no appreciable affinity for cholinergic muscarinic receptors. 129722-12-9 60795 C23H27Cl2N3O2 447.148030 White powder. 139-139.5°C Oral Aripiprazole's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia. Aripiprazole exhibits high affinity for dopamine D2 and D3, serotonin 5-HT1A and 5- HT2A receptors, moderate affinity for dopamine D4, serotonin 5-HT2C and 5-HT7, alpha1-adrenergic and histamine H1 receptors and moderate affinity for the serotonin reuptake pump. Aripiprazole has no appreciable affinity for cholinergic muscarinic receptors. Aripiprazole functions as a partial agonist at the dopamine D2 and the serotonin 5-HT1A receptors, and as an antagonist at serotonin 5-HT2A receptor. Aripiprazole is metabolized primarily by three biotransformation pathways: dehydrogenation, hydroxylation,and N-dealkylation.Based on in vitro studies,CYP3A4 and CYP2D6 enzymes are responsible for dehydrogenation and hydroxylation of aripiprazole, and N-dealkylation is catalyzed by CYP3A4.Aripiprazole is the predominant drug moiety in the systemic circulation. At steady-state, dehydro-aripiprazole, the active metabolite, represents about 40% of aripiprazole AUC in plasma (RxList, A308). Route of Elimination: Less than 1% of unchanged aripiprazole was excreted in the urine and approximately 18% of the oral dose was recovered unchanged in the feces. Half Life: 75-146 hours No indication of carcinogenicity to humans (not listed by IARC). For the treatment of schizophrenia and related psychotic disorders. Health effetcs include hyperpyrexia,muscle rigidity,altered mental status,and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Other effects may include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology (RxList, A308). No specific information is available on the treatment of overdose with aripiprazole. An electrocardiogram should be obtained in case of overdosage and if QT interval prolongation is present, cardiac monitoring should be instituted. Otherwise, management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms. Close medical supervision and monitoring should continue until the patient recovers. Consider charcoal and hemodialysis. (A308) 2009-07-15T20:47:50Z 2014-12-24T20:25:49Z Cytochrome P450 3A4 (CYP3A4) (P08684) (A308) Cytochrome P450 2D6 (CYP2D6) (P10635) (A308). Aripiprazole C12564 31236 Aripiprazole DB01238 true Cytochrome P450 3A4 (P08684) Cytochrome P450 2D6 (P10635) (A308) OC1=NC2=C(CC1)C=CC(OCCCCN1CCN(CC1)C1=CC=CC(Cl)=C1Cl)=C2 C23H27Cl2N3O2 InChI=1S/C23H27Cl2N3O2/c24-19-4-3-5-21(23(19)25)28-13-11-27(12-14-28)10-1-2-15-30-18-8-6-17-7-9-22(29)26-20(17)16-18/h3-6,8,16H,1-2,7,9-15H2,(H,26,29) InChIKey=CEUORZQYGODEFX-UHFFFAOYSA-N 448.385 447.148032537 Exogenous Solid 4.5 HMDB05042 CHEMBL1112 54790