Teratogenic and biochemical studies of the atypical antipsychotic, Aripiprazole on chick embryo

Aripiprazole is a third-generation atypical antipsychotic drug, typically used to treat schizophrenia, bipolar disorder, and treatment-resistant depression. Although its pharmacological profile has been well-characterized, its developmental toxicity remains poorly understood. Though it is classified as ‘Pregnancy Category C’ based on animal studies, this drug is the second-most-used antipsychotic drug among pregnant individuals.
The objective of our study was to evaluate the effects of Aripiprazole on chick embryonic development, with a focus on teratogenesis, vascular anomalies, and protein expression. Dose-response tests of a commercial Aripiprazole tablet at concentrations of 5 ppm and 10 ppm were performed on 3 distinct stages of development: HH stages 20-21 (72 hours or 3 days), HH stages 25-26 (120 hours or 5 days), and HH stages 33-34 (192 hours or 8 days). Each inoculation used 100 µl of the appropriate working solution, and the incubation period was 24 hours. The isolated embryos were checked for visible teratogenesis, fluctuations in protein and ALP levels.
The results showed varying degrees of, but irrefutable, teratogenic effects and impact on protein expression at all stages of development. Morphological analysis revealed dose-dependent malformations and growth retardation. The effects of the drug at these doses were observed to decrease as the developmental stage progressed. Tissue and vascular damage were documented, and biochemical evaluations revealed a trend of increase in total protein content with increasing drug concentration. Our findings allow us to conclude that Aripiprazole may not be safe for embryos. Further studies on mammalian models and/or cell lines are required.