A number of newly developed antiepileptic drugs are currently in use, among them Lamotrigine (LTG) is more common. Despite the extensive use of this drug, it has not been possible to predict the side effects especially the hepatotoxic reactions after long-term treatment. The present study was designed to find out alterations in the activities of liver enzymes after chronic exposure of rats to different dose of LTG. Adults male (Wistar) rats were treated orally with LTG [5 mg/kg body weight or 25mg/kg body wt.] for 60 days. After the experimental period, auto analyzer carried out liver function tests. The liver histopathology was obtained after scarifying the rats.There was a significant increase in the level of ALP, AST, ALT and bilirubin at therapeutic dose of LTG. The increase level of these enzymes and bilirubin at toxic dose were much higher and significant. However, the total protein and albumin significantly decreased at toxic dose of LTG. Elevation of liver enzymes and bilirubin after chronic exposure of rats to high dose of LTG reflects hepatocellular damage that may lead to hepatitis. It is concluded that regular liver function and drug monitoring should follow the treatment with LTG.

Levels of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) were estimated by HPLC in different regions of adult rat brain after feeding therapeutic (25 mg/kg) or toxic (100 mg/kg) doses of imipramine for 60 days. Imipramine (25 mg/kg) significantly enhanced the growth rate compared to control but the 100 mg/kg dose significantly reduced the body growth rate (but not brain weight) and in addition induced tremors, lethargy, hyperpigmentation and alopecia.Imipramine, 25 mg/kg, consistently decreased the levels of NE in cortex, striatum-accumbens, cerebellum and brainstem by about 24% (p < 0.01) and decreased DA levels in cortex, hippocampus and hypothalamus (p = 0.01). 5-HT levels were decreased in cortex, striatum-accumbens, hippocampus and brainstem by about 20% (p < 0.01) in imipramine-treated rats. On the contrary, 100 mg/kg of imipramine consistently increased NE levels in cortex, striatum-accumbens, hypothalamus (p < 0.01) and cerebllum (p < 0.05) and increased DA levels only in cerebllum by 39% (p = 0.01). Increased 5-HT levels were seen in all brain regions, of imipraminefed rats, by about 20% (p < 0.01). This study shows that the effects of imipramine on monoamine levels in brain is both region specific and dose dependent. The results suggest that decreased monoamine levels at 25 mg/kg of imipramine in humans might be responsible for the antidepressant effect of imipramine, and increased monoamine levels at higher doses might be responsible for various CNS toxic symptoms observed in patients with high doses of imipramine.