A novel GABA A alpha 5 receptor inhibitor with therapeutic potential
Send a publication request
close

Publication request

Thank you for your interest in our product range and your request for this publication, which will be sent to you if the research team and the journal allow it. Our commercial team will contact you as soon as possible.




- Categories : Miscellaneous research domains , Publications - ID: 763

Authors
Ling I, Mihalik B, Etherington LA, Kapus G, Pálvölgyi A, Gigler G et al.


Lab
Chemical Research Division, Egis Pharmaceuticals PLC, Budapest, Hungary.

Journal
Eur J Pharmacol.

Abstract
Novel 2,3-benzodiazepine and related isoquinoline derivatives, substituted at position 1 with a 2-benzothiophenyl moiety, were synthesized to produce compounds that potently inhibited the action of GABA on heterologously expressed GABAA receptors containing the alpha 5 subunit (GABAA ?5), with no apparent affinity for the benzodiazepine site. Substitutions of the benzothiophene moiety at position 4 led to compounds with drug-like properties that were putative inhibitors of extra-synaptic GABAA ?5 receptors and had substantial blood-brain barrier permeability. Initial characterization in vivo showed that 8-methyl-5-[4-(trifluoromethyl)-1-benzothiophen-2-yl]-1,9-dihydro-2H-[1,3]oxazolo[4,5-h][2,3]benzodiazepin-2-one was devoid of sedative, pro-convulsive or motor side-effects, and enhanced the performance of rats in the object recognition test. In summary, we have discovered a first-in-class GABA-site inhibitor of extra-synaptic GABAA ?5 receptors that has promising drug-like properties and warrants further development.

BIOSEB Instruments Used:
LabScribe 2.0 (LS-20)

Related products

Share this content