Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABA(A) [corrected] receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function.
The aim of the present paper was to study the effects of GABAA receptor-positive modulators (L-838417 and NS11394) showing a preference for α2/3 subunits of the GABAA receptor, in models of pain, anxiety, learning, memory and motor function. These compounds have been suggested to have a favourable therapeutic profile over nonselective compounds such as diazepam. In this study, we tested both compounds for their effects in rat models of formalin-induced pain, spinal nerve-ligation-induced mechanical allodynia, plus maze, open field, rotarod, balance beam walking, contextual fear conditioning and Morris water maze. Both compounds exerted analgesic, but no anxiolytic effects. However, they induced motor side-effects, and learning and memory impairment at similar doses. Therefore, the anxiolytic effect and the lack of side-effects of these compounds, as described in the literature, could not be confirmed in the present study.
Departments of In vivo Pharmacology, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.
Martine
M
Hofmann
Krisztina Sz
KS
Kordás
Andreas
A
Gravius
Kata
K
Bölcskei
Chris G
CG
Parsons
Andrzej
A
Dekundy
Wojciech
W
Danysz
László
L
Dézsi
Ina M
IM
Wittko-Schneider
Katalin
K
Sághy
István
I
Gyertyán
Csilla
C
Horváth
D000494:Allosteric Regulation; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001007:Anxiety / Q000188:drug therapy; D001562:Benzimidazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005239:Fear; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced; D009043:Motor Activity; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
C533864:3'-(5-(1-hydroxy-1-methylethyl)benzoimidazol-1-yl)biphenyl-2-carbonitrile; D000700:Analgesics; D001562:Benzimidazoles; D005464:Fluorobenzenes; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D014230:Triazoles; C409903:L 838,417