Evidence that 2-phenylpyrazolo[4,3-c]-quinolin-3(5H)-one antagonises pharmacological, electrophysiological and biochemical effects of diazepam in rats.
The effects of the acute administration of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one on diazepam-induced behaviour and electrophysiological activity were studied in rat. The compound, in doses of 5-10 mg/kg (i.p.), which per se did not induce alterations in spontaneous locomotor activity, antagonised the sedative effect induced by 5-10 mg/kg (i.p.) of diazepam. The injection of diazepam in rats, induced a profound reduction in the first negative wave of the recording of the visual evoked potential used as a sensitive electrophysiological test, in vivo. 2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (10 mg/kg, i.p.) caused a recovery of the amplitude of the first negative wave within a few minutes. This result was confirmed by the finding that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one, injected acutely in rats, pretreated with diazepam exhibited the capacity to antagonise the binding of [3H]diazepam determined in vitro on synaptic membrane preparations from cortex. The comparison of the pattern of the visual-evoked potential, recorded after the injection of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one (50 mg/kg) with the patterns recorded after the injection of ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazolo(1,5a) (1,4)benzodiazepine-3-carboxylate (50 mg/kg) and ethyl-beta-carboline-3-carboxylate and 1-methyl-beta-carboline demonstrated that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one is devoid of intrinsic activity.
Santi
M
M
Pinelli
G
G
Ricci
P
P
Penne
A
A
Zeneroli
M L
ML
Baraldi
M
M
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000378:metabolism; D003975:Diazepam / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005074:Evoked Potentials, Visual / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011720:Pyrazoles / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism
D011720:Pyrazoles; D011963:Receptors, GABA-A; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D003975:Diazepam