Referenced in: none

Automatically associated channels: Kir2.3

Title: Anxiolytic-like effects of PNU-101017, a partial agonist at the benzodiazepine receptor.

Authors: A H Tang, S R Franklin, D B Carter, V H Sethy, L M Needham, E J Jacobsen, P F Von Voigtlander

Journal, date & volume: Psychopharmacology (Berl.), 1997 Jun , 131, 255-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/9203236

Abstract
PNU-101017 is a chemically novel ligand at the benzodiazepine recognition site of cloned GABAA receptors. It was reported to potentiate GABA-mediated chloride current in cultured cells with a moderate intrinsic activity and a biphasic dose-response relationship. In this study, we confirmed that PNU-101017 has a partial agonist-like effect in the antagonism of metrazole-induced seizures in mice. It produced no sedation or ataxia, but did antagonize diazepam-induced motor deficit of mice in the rotarod test. PNU-101017 was weakly active in anti-conflict anxiolytic tests, but attenuated the plasma corticosteroid response to mild stress in rats. It also antagonized stress-induced elevation of cerebellar cGMP levels in mice. Like chlordiazepoxide, it increased drinking of saline solution in thirsty rats. PNU-101017 did not potentiate the CNS-depressant effects of ethanol, and produced no evidence of physical dependence when administered repeatedly. Agonists with low intrinsic activity at the benzodiazepine receptor, such as PNU-101017, should be further explored for therapeutic uses.