title: The novel GABA adamantane derivative (AdGABA): design, synthesis, and activity relationship with gabapentin.
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.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771 Athens, Greece. zoidis@pharm.uoa.gr
authors.forename: Grigoris
authors.initials: G
authors.lastname: Zoidis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Papanastasiou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Dotsikas
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sandoval
authors.forename: Raquel Gouvea
authors.initials: RG
authors.lastname: Dos Santos
authors.forename: Zeta
authors.initials: Z
authors.lastname: Papadopoulou-Daifoti
authors.forename: Alexander
authors.initials: A
authors.lastname: Vamvakides
authors.forename: Nicolas
authors.initials: N
authors.lastname: Kolocouris
authors.forename: Ricardo
authors.initials: R
authors.lastname: Felix
mesh_terms: 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
chemical_list: 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