The novel GABA adamantane derivative (AdGABA): design, synthesis, and activity relationship with gabapentin

A facile preparation of 2-aminomethyl-2-tricyclo[3.3.1.11,7]decaneacetic acid hydrochloride 5 (AdGABA) is described. The synthesis of AdGABA involves the hydrogenation of 2-cyano-2-tricyclo[3.3.1.11,7]decaneacetic acid 11, which was synthesized by two different synthetic routes. AdGABA was found to antagonize the pentylenetetrazole (PTZ) and semicarbazide (SCZ) induced tonic convulsions and exhibits analgesic activity in the hot plate test on mice. Although its mechanism of action is quite similar to that proposed previously for gabapentin (interaction with the α2δ subunit of the voltage gated Ca2+ channels), further studies were undertaken in order to clarify the precise mechanism of the anticonvulsant and analgesic effects of AdGABA on a molecular level.

In the current work, we report the design, synthesis (following two different synthetic routes), stability studies, and comprehensive pharmacology of a novel GABA adamantane derivative (AdGABA), which displays a close structure–activity relationship with gabapentin.Figure optionsDownload as PowerPoint slide