Early Preclinical Work Leading to the Development of Gabapentin

Gabapentin was conceived as part of a drug discovery program to treat neurological diseases, including epilepsy, spasticity, multiple sclerosis, and other central nervous system (CNS) disorders. This program began in the early 1970s at the German company, Goedecke, A.G., in Freiburg, Germany, which was a part of Warner-Lambert (now incorporated into Pfizer). The history of this project included chemical attempts to inhibit g-amino-butyric acid (GABA) degradation in brain with compounds that inhibited the catalytic pyridoxylphosphate of GABA-transaminase. It had already been known for some time that GABA was a key inhibitory neurotransmitter, and that experimental chemical impairment of GABA systems could cause seizures in experimental animals. The GABA transaminase project at Goedecke had progressed a compound to phase I clinical trials, but these were halted because of safety concerns. The chemical matter developed within the GABA transaminase project had no direct relationship to the chemical matter that led to gabapentin, although both had a similar conceptual approach based on GABA.

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