IDENTIFICATION OF NOVEL LIGANDS FOR THE GABAPENTIN BINDING-SITE ON THE ALPHA(2)DELTA SUBUNIT OF A CALCIUM-CHANNEL AND THEIR EVALUATION AS ANTICONVULSANT AGENTS

As part of a program to investigate the structure-activity relationshi ps of Gabapentin (Neurontin), a number of alkylated analogues were syn thesized and evaluated in vitro for binding to the Gabapentin binding site located on the alpha(2) delta subunit of a calcium channel. A num ber of other bridged and heterocyclic analogues are also reported alon g with their in vitro data. Two compounds showing higher affinity than Gabapentin were selected for evaluation in an animal model of epileps y. One of these compounds, (1S,3R)-(1-(aminomethyl)-3-methylcyclohexyl )acetic acid hydrochloride (19), was shown to be effective in this mod el with a profile similar to that of Gabapentin itself.