ACUTE, SUBCHRONIC, AND CHRONIC TOXICITY STUDIES WITH FELBAMATE, 2-PHENYL-1,3-PROPANEDIOL DICARBAMATE

Felbamate, 2-phenyl-1,3-propanediol dicarbamate, is a novel anticonvul sant that is effective against both chemically and electrically induce d seizures in laboratory animals. Acute, subchronic, and chronic studi es were conducted in mice, rats, and dogs to establish a preclinical s afety profile for this drug. Clinical signs following single intraperi toneal doses included hypoactivity, tremors, decreased muscle tone, at axia, prostration, and labored breathing. Death was observed after int raperitoneal but not oral administration. A consistent drug-related ef fect noted in all multiple-dose studies with this compound was decreas ed 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 accompani ed in some cases by increases in serum enzyme levels. No histopatholog ical changes were observed in the liver that could explain these eleva ted 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. (C) 1998 society of Toxicology.