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.