|Trade names||Vraylar (US), Reagila (EU)|
|Drug class||Atypical antipsychotic|
|Main uses||Schizophrenia, bipolar disorder|
|Side effects||Movement disorders, heart burn, sleepiness, restlessness|
|By mouth (capsules)|
|Typical dose||1.5 to 6 mg OD|
|Metabolism||Liver via CYP3A4 and to a lesser extent CYP2D6|
|Elimination half-life||2–5 days (2–3 wks for active metabolite, desmethylcariprazine)|
|Excretion||Urine (21%), bile|
|Chemical and physical data|
|Molar mass||427.41 g·mol−1|
|3D model (JSmol)|
Cariprazine, sold under the brand names Vraylar and Reagila, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken by mouth. Use is not recommended by Wales.
Common side effects include movement disorders, heart burn, sleepiness, and restlessness. Other side effects may include neuroleptic malignant syndrome, tardive dyskinesia, diabetes, weight gain, low white blood cells, low blood pressure with standing, and seizures. Use in older people with dementia increase the risk of death. Safety in pregnancy is unclear. It acts primarily on dopamine and serotonin receptors.
Cariprazine was approved for medical use in the United States in 2015 and Europe in 2017. In the United Kingdom 4 weeks of treatment costs the NHS about £80 as of 2021. This amount in the United States costs about 1,250 USD.
Cariprazine is used to treat schizophrenia and manic or mixed episodes, and depressive episodes associated with bipolar I disorder. Cariprazine consistently improved depressive symptoms across a spectrum of patients with bipolar I depression, and has been considered an effective and well tolerated treatment for the condition.
It is typically taken at a dose of 1.5 to 6 mg per day.
Side effects may first appear on the first day after starting cariprazine. The most prevalent side effects for cariprazine include akathisia, and insomnia. Cariprazine does not appear to impact prolactin levels, and unlike many other antipsychotics, does not increase the QT interval on the electrocardiogram (ECG). In short term clinical trials extrapyramidal effects, sedation, akathisia, nausea, dizziness, vomiting, anxiety, and constipation were observed. One review characterized the frequency of these events as "not greatly different from that seen in patient treated with placebo" but a second called the incidence of movement-related disorders "rather high".
Regarding side effects, the label of cariprazine states, "The possibility of lenticular changes or cataracts cannot be excluded at this time."
|Site||Ki (nM)||IA (%)||Action|
|The smaller the Ki value, the more strongly the drug binds to the site. IA=intrinsic activity.|
Unlike many antipsychotics that are D2 and 5-HT2A receptor antagonists, cariprazine is a D2 and D3 partial agonist. It also has a higher affinity for D3 receptors. The D2 and D3 receptors are important targets for the treatment of schizophrenia, because the overstimulation of dopamine receptors has been implicated as a possible cause of schizophrenia. Cariprazine acts to inhibit overstimulated dopamine receptors (acting as an antagonist) and stimulate the same receptors when the endogenous dopamine levels are low. Cariprazine's high selectivity towards D3 receptors could prove to reduce side effects associated with the other antipsychotic drugs, because D3 receptors are mainly located in the ventral striatum and would not incur the same motor side effects (extrapyramidal symptoms) as drugs that act on dorsal striatum dopamine receptors. Cariprazine also acts on 5-HT1A receptors, though the affinity is considerably lower than the affinity to dopamine receptors (seen in monkey and rat brain studies). In the same studies, cariprazine has been noted to produce pro-cognitive effects, the mechanisms of which are currently under investigation. An example of pro-cognitive effects occurred in pre-clinical trials with rats: rats with cariprazine performed better in a scopolamine-induced learning impairment paradigm in a water labyrinth test. This may be due to the selective antagonist nature of D3 receptors, though further studies need to be conducted. This result could be very useful for schizophrenia, as one of the symptoms includes cognitive deficits.
Cariprazine has partial agonist as well as antagonist properties depending on the endogenous dopamine levels. When endogenous dopamine levels are high (as is hypothesized in schizophrenic patients), cariprazine acts as an antagonist by blocking dopamine receptors. When endogenous dopamine levels are low, cariprazine acts more as an agonist, increasing dopamine receptor activity. In monkey studies, the administration of increasing doses of cariprazine resulted in a dose-dependent and saturable reduction of specific binding. At the highest dose (300 μg/kg), the D2/D3 receptors were 94% occupied, while at the lowest dose (1 μg/kg), receptors were 5% occupied.
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.
Society and culture
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