The novel GABA adamantane derivative (AdGABA): design, synthesis, and activity relationship with gabapentin.
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.
Zoidis
Grigoris
G
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771 Athens, Greece. zoidis@pharm.uoa.gr
Papanastasiou
Ioannis
I
Dotsikas
Ioannis
I
Sandoval
Alejandro
A
Dos Santos
Raquel Gouvea
RG
Papadopoulou-Daifoti
Zeta
Z
Vamvakides
Alexander
A
Kolocouris
Nicolas
N
Felix
Ricardo
R
D000085:Acetates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000218:Adamantane / Q000737:chemistry*; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D000077206:Gabapentin; D006801:Humans; D051379:Mice; D023421:Models, Animal; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D012663:Semicarbazides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013329:Structure-Activity Relationship; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C503772:2-aminomethyl-2-tricyclo(3.3.1.1(1,7))decaneacetic acid hydrochloride; D000085:Acetates; D000588:Amines; D000700:Analgesics; D000927:Anticonvulsants; D015220:Calcium Channels; D003509:Cyclohexanecarboxylic Acids; D012663:Semicarbazides; C010059:carbamylhydrazine; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D000218:Adamantane; D010433:Pentylenetetrazole