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

Bioorg Med Chem. 2005 Apr 15;13(8):2791-8. doi: 10.1016/j.bmc.2005.02.030.

Abstract

A facile preparation of 2-aminomethyl-2-tricyclo[3.3.1.1(1,7)]decaneacetic acid hydrochloride 5 (AdGABA) is described. The synthesis of AdGABA involves the hydrogenation of 2-cyano-2-tricyclo[3.3.1.1(1,7)]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 alpha2delta 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates* / chemical synthesis
  • Acetates* / chemistry
  • Acetates* / pharmacology
  • Adamantane / chemistry*
  • Amines / chemistry
  • Amines / pharmacology*
  • Analgesics* / chemical synthesis
  • Analgesics* / chemistry
  • Analgesics* / pharmacology
  • Animals
  • Anticonvulsants* / chemical synthesis
  • Anticonvulsants* / chemistry
  • Anticonvulsants* / pharmacology
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cyclohexanecarboxylic Acids / chemistry
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Drug Design
  • Gabapentin
  • Humans
  • Mice
  • Models, Animal
  • Molecular Structure
  • Pentylenetetrazole / antagonists & inhibitors
  • Pentylenetetrazole / pharmacology
  • Rats
  • Semicarbazides / antagonists & inhibitors
  • Semicarbazides / pharmacology
  • Structure-Activity Relationship
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / chemical synthesis
  • gamma-Aminobutyric Acid / chemistry
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • 2-aminomethyl-2-tricyclo(3.3.1.1(1,7))decaneacetic acid hydrochloride
  • Acetates
  • Amines
  • Analgesics
  • Anticonvulsants
  • Calcium Channels
  • Cyclohexanecarboxylic Acids
  • Semicarbazides
  • carbamylhydrazine
  • gamma-Aminobutyric Acid
  • Gabapentin
  • Adamantane
  • Pentylenetetrazole