Acute, subchronic, and chronic toxicity studies with felbamate, 2-phenyl-1,3-propanediol dicarbamate

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvulsant that is effective against both chemically and electrically induced seizures in laboratory animals. Acute, subchronic, and chronic studies were conducted in mice, rats, and dogs to establish a preclinical safety profile for this drug. Clinical signs following single intraperitoneal doses included hypoactivity, tremors, decreased muscle tone, ataxia, prostration, and labored breathing. Death was observed after intraperitoneal but not oral administration. A consistent drug-related effect noted in all multiple-dose studies with this compound was decreased body weight and food consumption. The only other consistent change noted in multiple-dose studies with felbamate was an increase in liver weight (relative and absolute) in the rat and dog which was accompanied in some cases by increases in serum enzyme levels. No histopathological changes were observed in the liver that could explain these elevated serum enzyme levels. Based on the results of these studies it was concluded that long-term administration of felbamate in human clinical trials was warranted.