CGS 8216: Receptor binding characteristics of a potent benzodiazepine antagonist

Non-xanthine heterocycles: Activity as antagonists of A1 and A2-adenosine receptors

“…A more extensive series of such heterocycles including the parent compound without an aryl substituent would be required before interpretations can be advanced. The 2-phenyl-pyrazoloquinolinone CGS 8216 (X) has been reported to have a K i value of 1.3 μM versus binding of [ 3 H]cyclohexyladenosine to A 1 receptors in rat brain membranes and to have a K i value of 3.1 μM versus A 2 -receptor stimulation of cyclic AMP accumulation in guinea pig brain vesicular preparations [15,22]. This heterocycle has much more potent activity as a benzodiazepine antagonist at the GABA-receptor channel complex [22], The furyl-substituted triazoloquinazoline CGS 15943a (XIII) has been proposed as a very potent A 2 -selective adenosine receptor antagonist [24], In the present study, CGS 15943a was found to be very potent at both A 1 and A 2 receptors (Table 1).…”

“…Other classes of heterocyclic compounds exhibit antagonist activity at adenosine receptors. These include: 9-methyladenines [10,14], various pyrazolopyridines (etazolate, cartazolate, tracazolate) [15][16][17][18], various pyrazolopyrimidines [19,20], imidazopyrazines [21], a phenyl-substituted pyrazoloquinoline (CGS 8216) [22,23], a furyl-sub-stituted triazoloquinazoline (CGS 15943a) [24], a triazolopyridazine (CL218872) [15], various mesoionic analogs of xanthines [25], pteridin-2,4-diones (lumazine) and benzopteridin-2,4-diones [10,26], β-carbolines [15,27], barbiturates [28,29] and dibenzazepines (carbamazepine) [30][31][32][33]. A phenylaminoimidazoline, clonidine, has been reported to antagonize adenosine responses in physiological experiments [34].…”

The Ro 15–1788 cue: Evidence for benzodiazepine agonist and inverse agonist properties

“…The barbiturates pentobarbital and phenobarbital, the non-specific or specific BDZ antagonists pentylenetetrazol, fl-CCM and CGS 8216 (Czernik et al, 1982;Haefely et al 1983) and the quinoline derivative PK 8165 (LeFur et al, 1981) induced partial generalization with Ro 15-1788. Generalization was more than 40% with these substances but failed to reach the maxima obtained with the BDZs even at the highest doses which could be tested (table 1).…”

Behavioral pharmacological profile of CGS 9895: A novel anxiomodulator with selective benzodiazepine agonist and antagonist properties

“…1) has generated particular interest because different neurochemical and behavioral properties result from minor molecular modifications [Czernik et al, 1982;Gee and Yamamura, 1982;Yokoyama et al, 19821. CGS 8216 is a benzodiazepine antagonist [Bernard et al, 1981 ;Yokoyama et al, 1982;Boast et al, 1983;Spencer and Lal, 19831 with some suggestion of weak benzodiazepine inverse agonism [File and Lister, 1983;Boast et al, 19831.…”