Teratogenic effects of cariprazine hydrochloride, a new antipsychotic, on xenopus laevis embryos

Aim: Atypical antipsychotics are drugs that can be used for long periods of time in the patient groups for which they are indicated and its use is increasing in the pregnant patient population. Cariprazine is one of the newest members of atypical antipsychotic drugs, and its major metabolites, which are pharmacologically active, can be detected in plasma long after drug use has been discontinued. This should be taken into consideration in patients planning pregnancy or who are pregnant. In our study, we investigated the possible teratogenic effects of cariprazine and its metabolite didesmethyl-cariprazine on Xenopus laevis embryos. Material and Method: X. laevis tadpoles were exposed to cariprazine and its primary metabolite didesmethyl cariprazine at concentrations of 1 nM, 10 nM, 100 nM, 1000 nM and 10000 nM by the FETAX method. Afterwards, the tadpoles were subjected to behavioral testing. After euthanasia, tadpoles were examined histopathologically. Additionally, qPCR was applied to measure the expression levels of myf5, esr1, bmp-4, pax6, hsp70 and fmr1 genes. Findings: There was no significant difference in the developmental stages and frequency of congenital malformations or deaths of X. laevis tadpoles among the groups. In length measurements, a statistically significant shortening was observed in tadpoles in the 10000 nM group compared to the control and other groups. In histopathological examinations, no change was observed between the control and treatment groups. In qPCR measurements, a dose-related increase was observed in pax6 and fmr1 genes. Although this increase was interrupted in the 100 nM group of pax6 and in the 100 nM and 1000 nM groups of fmr1, it resulted in a more than 5-fold increase in the expression of both genes in the 10000 nM group. Conclusion: Our study suggests that cariprazine may be safe in therapeutic doses in X laevis embryos. Behavioral tests also support this. However, further studies are needed to reach a definitive conclusion on the effects of cariprazine on human embryo development.