Pharmacological analysis of the activity of phenazepam and flunitrazepam administered in superlow doses

Молодавкин, Г. М.; Burlakova, E. B.; Chernyavskaya, L. I.; Воронина, Т. А.; Khorseva, N. I.; Seredenin, S. B.

doi:10.1007/bf02446622

Cited by 6 publications

(7 citation statements)

References 6 publications

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“…In support of our previous observations [3], both usual and superlow doses o f phenazepam increased the number of punished drinkings in the conflict test (Table 1), the effect of usual doses was much more pronounced.…”

Section: Resultssupporting

confidence: 90%

“…These agents are usually effective in the plus-maze test [8,14,15], and side effects typical of potent benzodiazepines with these drugs are less pronounced o1 absent [14,15]. Previous studies showed [3] that in a conflict situation phenazepam administered in super- low doses acts similarly to anxioselective drugs: it is effective in weak punishing current (0.5 mA) and ineffective in stronger current (1 mA). In these doses the tranquilizer has no side effects.…”

Section: Resultsmentioning

confidence: 99%

“…It has been previously demonstrated that phenazepam in low doses (up to 10 -1~ mol/kg) exerts a pronounced anxiolytic effect under conditions of a conflict situation without inducing adverse effects [3].…”

Section: Abstract: Tranquilizers; Phenazepam; Superlow Doses; Eeg; Amentioning

confidence: 99%

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Effect of superlow doses of phenazepam on the EEG and behavior of rats in different models of anxiety

et al. 1997

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Phenazepam administered in superlow doses exerts an anxiolytic effect in albino male rats under conditions of plus-maze and conflict test and induces typical inhibition of 0-activity in the EEG. Contrary to the effect of usual doses, other frequency intervals remain practically unchanged. Phenazepam in superlow doses acts as an anxioselective tranquilizer. Key Words: tranquilizers; phenazepam; superlow doses; EEG; anxiolytic activitySince benzodiazepines usually have various side effects, new approaches to pharmacotherapy of neurosis-like and borderline-neurotic states are directed toward anxioselectivity of the treatment. It has been previously demonstrated that phenazepam in low doses (up to 10 -1~ mol/kg) exerts a pronounced anxiolytic effect under conditions of a conflict situation without inducing adverse effects [3].Our goal was to evaluate electrophysiological effects of low doses of phenazepam and their relationship with rat behavior in different models of anxiety. MATERIALS AND METHODSExperiments were carried out on random-bred albino male rats with initial body weight of 200-220 g.The EEG was recorded under conditions of free behavior [6] using a Neurograph 18-channel electroencephalograph (O.T.E. Biomedica) with amplifiers set at a standard mode: 0. After initial habituation, the background EEG was recorded for 5 min. Phenazepam (10 -1~ mol/kg) was administered intragastrally through a tube; EEG was recorded and analyzed every 15 rain during the first hour and then every hour. Control animals received placebo according to the same scheme. The effects of phenazepam administered in superlow and usual doses were compared.Anxiolytic activity of phenazepam was assessed in the standard conflict test [5,13] and in elevated plus-maze test [9].The conflict situation test is based on a conflict between drinking motivation and painful electrical stimulation in water-deprived animals. A considerably increased number of punished drinkings in the experimental group in comparison with the control served as a measure of the effect.The

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

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Effect of superlow doses of phenazepam on the EEG and behavior of rats in different models of anxiety

et al. 1997

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“…The effect was evaluated by statistically significant increase in the number of punished water takings in the control group rats in comparison with the punished control group at an electrical current strength of 0.5 or 1 mA. The effects of preparations on motor activity were assessed visually by the number of erossings of the lines, which were drawn on the floor under the electrode wires spaced at 5 cm [5].The EEG was recorded under unrestrained behavioral conditions from the rats in which Nichrome electrodes were implanted into the hippocampus and frontal cortex under local anesthesia and Nembutal narcosis (40 mg/kg). The reference electrode was fixed in the nasal bones.…”

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Behavioral and electrophysiological analysis of anxiolytic effect of mongolian astragalus

et al. 1998

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Medical herb Mongolian astragalus has anxiolytic activity in conflict situation imposed on random-bred male albino rats, and evokes changes in electroencephalogram which are characteristic of tranquilizers. The drug moderates the x-rhythm in cerebral hemispheres and hippocampus. In contrast to benzodiazepine tranquilizers, it does not affect the frequencies in other bands. Key Words: medical herbs; anxiolytic effect; conflict situation; electroencephalogramMedical herbs are widely used in the therapy of neurotic and borderline-neurotic states as sedative [4] and supporting [2] preparations. Since the drugs used in the treatment of these diseases produce unfavorable side-effects, some medical herbs may be prospective as minor daytime tranquilizers. This paper deals with anxiolytie effect of Mongolian astragalus (MA), which is a herb of the leguminous family growing in Russia and Mongolia. The mechanism of MA action was examined by analysis of changes in the electroencephalogram (EEG). MATERIALS AND METHODSThe study was carried out on random-bred male albino rats weighing 200-250 g.Anxiolytic activity was examined on the model of conflict situation based on antagonism (conflict) of drinking motivation and electrical noeieeptive stimulation [12]. The study used a multichamber setup developed at the Laboratory of Psyehopharmacology of the Institute of Pharrnaeology, Russian Academy of Medical Sciences [6]. After deprivation and conditioning to drink from a drinking bowl, the rats were arbitrary subdivided into the following groups: nonpunished control group, in which rats were given distilled water with no electrical current Institute of Pharmacology, Ru~nn Academy of Medical Sciences, Moscow; Institute of Folk Medicine, Ulan-Bator applied to the drinking bowl (this group was used to estimate motor activity and drinking motivation on the day of experiment); punished control group, in which rats were given water, but electrical current was applied to the drinking bowl; three groups of rats, in which MA was administered in increasing doses; and three groups of rats, in which increasing doses of phenazepam (a control drug) were given. The effect was evaluated by statistically significant increase in the number of punished water takings in the control group rats in comparison with the punished control group at an electrical current strength of 0.5 or 1 mA. The effects of preparations on motor activity were assessed visually by the number of erossings of the lines, which were drawn on the floor under the electrode wires spaced at 5 cm [5].The EEG was recorded under unrestrained behavioral conditions from the rats in which Nichrome electrodes were implanted into the hippocampus and frontal cortex under local anesthesia and Nembutal narcosis (40 mg/kg). The reference electrode was fixed in the nasal bones. On postoperative days 7-10 (restoration period surgery operation and narcosis) the EEG was recorded with the help of a Neurograph 18-channel electroencephalograph (O.T.E. Biomediea), with amplifiers tuned for the standard...

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“…Experimental studies of bipathic mode of drug administration showed that phenazepam in ultralow doses (10 -9 -10 -14 mol/kg) exhibited a pronounced anxiolytic effect, not accompanied by side effects characteristic of benzodiazepine tranquilizers (myorelaxant and sedative) [1,2,4].…”

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Study of bipathic effect of haloperidol

et al. 2008

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Pharmacological analysis of the activity of phenazepam and flunitrazepam administered in superlow doses

Cited by 6 publications

References 6 publications

Effect of superlow doses of phenazepam on the EEG and behavior of rats in different models of anxiety

Effect of superlow doses of phenazepam on the EEG and behavior of rats in different models of anxiety

Behavioral and electrophysiological analysis of anxiolytic effect of mongolian astragalus

Study of bipathic effect of haloperidol

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