Antiexudative Effects of Finasteride and a New Pyrazolo[C]Pyridine Derivative GIZh-72 in Acetic Acid-Induced Experimental Peritonitis.

It was shown that finasteride, a 5α-reductase inhibitor (50 mg/kg, intraperitoneally) produced analgesic and antiexudative effects in experimental peritonitis induced by intraperitoneal injection of 1% acetic acid. These results agree with published data on its anti-inflammatory properties and ability to potentiate the analgesic effect of morphine in rodents. New pyrazolo[C] pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]pyridine-3-on, chloral hydrate) injected intraperitoneally in doses of 20-80 mg/kg produced dose-dependent antiexudative effects, but exhibited no analgesic properties.

Psychotropic Effects of a New Pyrazolo[C]Pyridine Derivate GIZh-72 are Related to Functional Activity of Atp-Sensitive Potassium Channels.

We studied the influence of intraperitoneal injection of ATP-sensitive potassium channels inhibitor glibenclamide in doses of 0.01, 0.1, 1, and 10 mg/kg on the effects of a new pyrazolo[C]pyridine derivative GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1Hpyrazolo[ 4,3-C]pyridine-3-on, chloral hydrate; 20 mg/kg, intraperitoneally) in the marble burying and open-field tests in mice. It was found that glibenclamide produced an anxiolytic effect in the open-field test (in a dose of 0.01 mg/kg) and anticompulsive effect in the marble burying test (in doses of 1 and 10 mg/kg). The observed behavioral effects of glibenclamide did not depend on blood glucose level. At the same time, glibenclamide in subeffective (0.01 and 0.1 mg/kg) and effective (1 and 10 mg/kg) doses potentiated the psychotropic effects of GIZh-72 in these tests. It can be assumed that the psychotropic effects of GIZh-72 depend on functional activity of ATP-sensitive potassium channels.

Anticompulsive Activity of a New Pyrazolo[C]Pyridine Derivative GIZh-72 under Conditions of Unpredictable Chronic Mild Stress.

Anticompulsive activity of a novel compound GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]Pyridine-3-on, chloral hydrate) in a dose of 20 mg/kg (single, subchronic, and chronic administration) in comparison with fluvoxamine (25 mg/kg) was studied in the marble burying test in the model of unpredictable chronic mild stress on BALB/c mice. GIZh-72 produced an anticompulsive effect that increased with increasing treatment duration under stress conditions in contrast to fluvoxamine that induced inversion of this effect after long-term administration. Neuroleptic activity of GIZh-72 in doses of 20 and 40 mg/kg was studied on the model of apomorphine-induced climbing in C57Bl/6 mice. In contrast to haloperidol (0.5 mg/kg), GIZh-72 exhibited no neuroleptic properties. Our results indicate that GIZh-72 holds much promise for pharmacotherapy of obsessive-compulsive disorder.

[THE STUDY OF ANXIOLYTIC PROPERTIES OF NEW PYRAZOLO[C]PYRIDINE DERIVATIVE GIZH-72].

It was studied the anxiolytic properties of 4,6-dimethyl-2-(4-chlorophenyl)-2,3-dihydro-1Í-pyrazolo[4,3-c]pyridin-3-one chloralhydrate (GIZh-72, 20 mg/kg, i.p.) and afobazole (1 mg/kg, i.p.) in comparison to fluoxetine (20 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) in open-field and marble burying tests on male mice of inbred strains BALB/C and C57BL/6. It is established that GIZh-72 administered both 30 min and 24 h before testing produces anxiolytic effect in the open-field test. The open field anxiety response patterns following GIZh-72 administration differed from these in diazepam or afobazole treated BALB/C mice. This drug also decreased the number of buried marbles in both BALB/C and C57BL/6 mice, the effect being comparable to that of afobazole and fluoxetine. In operant drug discrimination liquid-reinforcement paradigm in male Wistar rats, GIZh-72 failed to antagonize or substitute for the interoceptive stimulus cues of pentylenetetrazole evoking the saline-like responses in the latter case, which was evidence for the absence of properties of a ligand bearing positive modulator sites of GABA-A receptor.

[Behavioral and radioreceptor analysis of viloxazine stereoisomers]. / Povedencheskii i radioprotektornyi analiz stereoizomerov viloksazina.

The differences in the pharmacological effects of R(+)- and S(-)-isomers of the atypical antidepressant viloxazin were discovered in two behavioral models. The S(-)-isomer appeared 5 times as active as the R(+)-isomer under acute administration. In chronic administration, (15 days), the R(+)-isomer appeared ineffective. Comparison of the affinity of the racemate, R(+) and S(-)-isomers for alpha 1-, alpha 2- and beta-adrenoreceptors, as well as for serotonin, C1, benzodiazepine, imipramine and dopamine receptors did not demonstrate any stereospecificity of viloxazin isomers. It is assumed that some other receptors (histamine, acetylcholine) present the targets for the pharmacological action of viloxazin or the latter one has, like zimelidin , specific binding sites of its own.

[Pharmacological characteristics of a new phenyl analog of piracetam--4-phenylpiracetam]. / Farmakologicheskaia kharakteristika novogo fenil'nogo analoga piratsetama--4-fenilpiratsetama.

The central neurotropic effects of 4-phenylpyracetam, a new phenyl analog of pyracetam, were studied and compared with the effects of pyracetam, morpholene and 4-phenylpyrrolidone. 4-Phenylpyracetam was found to activate the operant behavior more powerfully, to remove psychodepressant effects of diazepam, to inhibit post-rotational nystagmus, and to prevent the development of retrograde amnesia. Unlike pyracetam, 4-phenylpyracetam exhibits a specific anticonvulsant action. When given in high doses, the compound under study produces psychodepressant effects.