Cariprazine (RGH-188, 
trans-4-{2-[4-(2,3-dichlorophenyl)-piperazine-1-yl]-ethyl}-N,N-dimethylcarbamoyl-cyclohexyl-amine 
hydrochloride), is a novel antipsychotic with dopamine D2 and D3 receptors 
antagonist-partial agonist properties. Cariprazine has also moderate affinity 
for serotonin 5-hydroxytryptophan (5-HT) 1A receptors, high affinity for 5-HT1B 
receptors with pure antagonism and low affinity for 5-HT2A receptors. 
Randomized, double blind, placebo controlled, flexible-dose (3-12 mg/day) 
studies have demonstrated cariprazine is effective in both schizophrenia and 
acute manic episodes associated with bipolar disorder. The incidence of serious 
adverse events in cariprazine arm was no different than in placebo arm in these 
studies. The most common adverse events were extrapyramidal symptoms, headache, 
akathisia, constipation, nausea, and dyspepsia which can be explained with 
cariprazine's partial dopamine agonism. Although cariprazine treatment was 
associated with a higher incidence of treatment-emergent adverse events, 
particularly akathisia and tremor, common side effects of marketed second 
generation antipsychotics such as weight gain, metabolic disturbances, prolactin 
increase or QTc prolongation were not associated with cariprazine, probably due 
to its moderate to low binding affinity for histamine H1 and 5-HT2C receptors. 
Animal studies show that cariprazine may have additional therapeutic benefit on 
impaired cognitive functioning with D3 receptor activity, however clinical data 
is still scarce. The aim of this article is to review the potential use of 
cariprazine for the treatment of acute manic episodes in the light of the 
preclinical and clinical trials reported to date.