Pharmacology of the pyrazolo-type compounds: Agonist, antagonist and inverse agonist actions

Towards functional selectivity for α6β3γ2 GABAA receptors: a series of novel pyrazoloquinolinones

“…Residue modifications led to varying neurochemical and behavioural properties. For example, compound 1 (CGS9895; R '4 = methoxy; see Figure ) (Ramerstorfer et al, ; Varagic et al, ) not only antagonized the effects of diazepam but also showed anxiolytic and weak anticonvulsant activity while being devoid of sedation, muscle relaxation or motor impairments (Bennett et al, ; Bennett, ). These findings encouraged the possibility of separately eliciting only specific desired BZD‐like effects (Kolata, ).…”

“…These findings encouraged the possibility of separately eliciting only specific desired BZD‐like effects (Kolata, ). Early on, researchers noted a dissociation between BZD receptor activity and the in vivo pharmacology of PQs (Bennett, ; Cooper et al, ).…”

Ligands of the GABAA Receptor Benzodiazepine Binding Site

“…CGS8216 was originally considered to be an antagonist for the BZ-binding site (49,51), but recent studies suggest that it possesses a weak inverse agonist efficacy (7,52). CGS9895 and CGS9896 are partial agonists (51,53); however, CGS9895 displays a lower agonist efficacy than CGS9896 (53). The structure-efficacy relationship of these three analogs further suggests that unsubstituted 2-phenyl pyrazoloquinolines (such as CGS8216) are characterized by a lower intrinsic efficacy than substituted 2-phenyl pyrazoloquinolines (such as CGS9895 and CGS9896).…”

Pyrazoloquinolines and zolpidem: Effects on hypertonic saline consumption in rehydrating rats

“…CGS 17867A also shows high-affinity binding to benzodiazepine sites, is active in the Cook-Davidson conflict model, antagonizes the pentylenetetrazol (FTZ) discriminative cue, and blocks PTZ-induced convulsions in rats. Likc CGS 9895 and CGS 9896, CGS 17867A is devoid of sedativeimuscle relaxant effects, but differs from them in not antagonizing the diazepam discriminative stimulus or a diazepam-induced rotorod deficit [Bennett, 1987;Bennett et al, 19861. The second main aim of the present series of cxperiments was to evaluate CGS 17867A in the test of hypertonic saline ingestion for agonist or antagonist activity.…”

“…A saturated version of CGS 9896 has recently been described [Bennett, 1987;Bennett et al, 19861. CGS 17867A also shows high-affinity binding to benzodiazepine sites, is active in the Cook-Davidson conflict model, antagonizes the pentylenetetrazol (FTZ) discriminative cue, and blocks PTZ-induced convulsions in rats.…”