Aripiprazole is an atypical antipsychotic used in the treatment of a wide variety of mood and psychotic disorders, such as schizophrenia, bipolar I, major depressive disorder, irritability associated with autism, and Tourette's syndrome. Aripiprazole may be administered with or without food and is available in oral tablets, disintegrating tablets (10 mg and 15 mg), oral solution, and intramuscular (IM) injections for acute symptoms and long-acting IM injections. Aripiprazole is a quinolinone antipsychotic that is a partial agonist at the D2 and 5HT-1a receptors and an antagonist at the 5HT-2a receptor. It has a high affinity for D2, D3, 5HT-1a, and 5HT2a receptors and moderate affinity for D4, 5HT-2c, 5-HT7, alpha-1 adrenergic, and H1 receptors. Aripiprazole has no affinity for muscarinic receptors at recommended doses. It stabilizes dopamine and serotonin within the nucleus accumbens, ventral tegmental area, and frontal cortex resulting in the management of positive, negative, and cognitive symptoms in schizophrenia. Aripiprazole demonstrates functional selectivity in intracellular signaling pathways by requiring a greater than 90% occupancy rate at D2 receptors to be clinically active, thus not producing as many extrapyramidal symptoms. Aripiprazole will act as a functional antagonist in areas of high dopamine, such as the mesolimbic pathway, while remaining inactive in areas with normal dopamine, such as the nigrostriatal and tuberoinfundibular pathways. The partial agonism of aripiprazole at D2 receptors may be responsible for the effective management of positive, negative, and cognitive symptoms of schizophrenia. Research has shown that it has more selective effects on the mesolimbic dopaminergic pathway than haloperidol and olanzapine. Although the side effects of aripiprazole are similar to those found in typical and atypical antipsychotics, the degree of extrapyramidal symptoms (EPS) and metabolic syndromes are less due to receptor specificity. Aripiprazole is associated with lower incidences of weight gain, hypercholesterolemia, glucose dysregulation, cardiovascular abnormalities, and hyperprolactinemia.

Aripiprazole Serotonin Agonist Pathway References