Neuroembryopathic effect of clobazam in rat: a histological study

Clobazam is a derivative of the benzodiazepines used as an anti-epileptics drug. The pregnant rat had received, orally, 125 mg/kg of clobazam daily from 1st-7th day of gestation and fetuses were collected on 20th day of pregnancy. Brain of the clobazam treated fetuses showed no significant change in weight and size in comparision to that of the controls. Other gross abnormalities were also not found in the brains of treated group. Histological examination revealed the alteration in cytoarchitecture of the cerebral and the cerebellar cortex. Strips of focal coagulate necrosis extended through most of the layers of the cerebral cortex. There were paucity of neurons and neurological elements in the cortex and the central grey area of spinal cord. Many of these neurons showed pyknotic nuclei. The intercellular spaces increased either because of decrease in cell number or due to shrinkage and clumping of degenerated neurons. Subcortical (white matter) zone showed the paucity and derangement of the oligodendrocytes and the astrocytes, which revealed vigorous proliferation in the treated group. These findings showed that the benzodiazepines and their derivatives have teratogenic effect in the developing mammalian central nervous system.