75% in the putamen". Cariprazine, as well as other third generation antipsychotics possesses a lower chance of exacerbating extrapyramidal symptoms. However the ability to induce akathasia remains relatively high. This may be mediated through a lack of anticholinergic effects (as agents of this class undo akathasia sometimes), as well as a lack of a balanced dopaminergic/serotonergic ratio (compared to the second generation antipsychotics serving a more nuanced profile in this regard). Moreover partial agonists though their limited response triggering ironically often have the tendency to occupy near all targeted receptors at relatively low dosages of the drug. An extrem example is ariprizole with an average occupancy of 70% at a 2mg dose, way below its usual antipsychotic dosage (to think of, that the often citated treshold of occupancy for an antipsychotic effect is 70%). This could possibly be one more reason for akathasia from partial agonists. Pharmacokinetics Cariprazine has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic. In rats, the oral bioavailability was 52% (with a dose of 1 mg/kg). Cariprazine is metabolized primarily by the cytochrome P450 3A4 isoenzyme (CYP3A4), with some minor metabolism by CYP2D6. Cariprazine does not induce the production of CYP3A4 or CYP1A2 in the liver, and weakly, competitively inhibits CYP2D6 and CYP3A4. Research Positive Phase III study results were published for schizophrenia and mania in early 2012, and for bipolar disorder I depression from a Phase II trial in 2015. Cariprazine is also potentially useful as an add-on therapy in major depressive disorder. It is being developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the U.S., Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela). In February 2022, AbbVie requested approval by the US Food and Drug Administration (FDA) for adjunctive treatment for major depressive disorder. Approval was granted by the FDA in December 2022, for cariprazine to be used as an adjunctive treatment for major depressive disorder. References External links 2,3-Dichlorophenylpiperazines AbbVie brands Atypical antipsychotics Dimethylamino compounds Dopamine antagonists H1 receptor antagonists Mood stabilizers Serotonin receptor antagonists Ureas