Exploring Various Crystal and Molecular Structures of Gabapentin—A Review

Abstract

Novel antiepileptic drugs have been developed at an unparalleled rate during the past 15 years. Gabapentin (GBP), which was approved for the treatment of refractory localization-related epilepsies in the U.K. and Europe in 1993, was one of the first drugs to come out of this era. Since then, GBP has become well-known across the world, not only for its antiepileptic qualities but also for its effectiveness in the treatment of chronic pain disorders, particularly neuropathic pain. In this review, the crystal structures of GBP and GBP-related compounds have been analyzed and compared. Particular attention has been paid to the polymorphism of GBP and its hydrates, their thermodynamic stability, and conformational differences. In addition, the puckering parameters for the cyclohexane ring of a total of 118 molecules of GBP found in the analyzed crystal structures have been calculated and analyzed. The results of recent high-pressure crystallization studies and quantum chemical calculations indicate that the entire landscape of GBP has not been revealed yet.