The study examined the effect of 9-(2-morpholinoethyl)-2-(4-fluorophenyl)imidazo[1,2-α] benzimidazole dihydrochloride (RU-1205) on the latency of seizures provoked by corazol, bicuculline, or picrotoxin. This agent (10 and 20 mg/kg) increased the seizure latency in the experimental models of epileptogenesis. The blockers of GABA and GABA -ρ receptors picrotoxin and (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid, respectively, were employed to study the effects of RU-1205 on electrical activity of somatosensory cortical neurons and on formation of pathological rhythms in the rat brain. RU-1205 inhibited the focal background rhythm and eliminated the epileptiform activity, which can be mediated by interaction with GABA receptors.
Antiepileptic activity of a new derivative of benzimidazole RU-1205 was studied on the model of pentylenetetrazole-induced generalized seizures in mice. Sodium valproate was used as the reference substance. RU-1205 was superior to sodium valproate by anticonvulsant activity (by 12 times) and therapeutic index (by 8.5 times). In contrast to sodium valproate, RU-1205 exhibited significant anticonvulsant activity on the model of pentylenetetrazole-induced kindling without tendency to resistance development.
Since ischemic stroke is an extremely common and dangerous pathology, it is important to use drugs with neuroprotective activity. The depth and degree of brain damage due to ischemia are reflected in its bioelectrical activity. This makes it possible to use the electrocorticography or intracranial electroencephalography (EEG) as a tool for evaluating the effectiveness of neuroprotective therapy. In the present study the neuroprotective properties of the experimental compound RU-1205 and the kappa-opioid agonist butorphanol were analyzed. The neuroprotective effect of the substances was assessed by measuring the extent of the neurological deficit and the changes in bioelectrical activity of the ischemic brain of rats. Compound RU-1205 (10 mg/kg, i.v.) as well as the reference drug butorphanol (2,5 mg/kg, i.v.) restored to normal neurological status and power of the EEG signal in delta and theta frequency bands.
Background. Schizophrenia is a socially signifi cant disease that takes a variety of forms. The form of the course determines prescribing antipsychotic drugs with a different range of clinical effects. The study of the pharmacological activity of neuroleptics involves an experimental model using animals which makes it possible to reproduce some aspects of schizophrenia.Objectives. The study is aimed at evaluating the antipsychotic activity of 5-HT2A— RU-31 antagonist and atypical neuroleptic clozapine in behavioral tests and electroencephalography (EEG).Methods. The research methodology involved a dysontogenetic model of schizophrenia, implemented via aspiration destruction of the ventral hippocampus of rats on day 7 of postnatal development. The study was carried out on white outbred male rats selected from the offspring of females, represented by a simple random sample, provided by Rappolovo animal breeding facility of the National Research Center “Kurchatov Institute”. Injection of the studied substances was initiated on day 35 of postnatal development. Motor activity was assessed on day 54 of postnatal development in the Open Field unit and included assessing vertical motor activity, measured as the number of acts of verticalization in 5 minutes, and horizontal motor activity of rats, recorded as the number of crossed squares in 5 minutes. EEG signals were recorded on day 55 of postnatal development; thereafter the spectral density was calculated in the delta- (д) (0.4–4 Hz), theta- (и) (4.8–8 Hz), alpha- (б) (8–12 Hz) and beta- (в) (12–30 Hz) frequency ranges and the effect of the “operation” and “substance” factors on spectral density was evaluated in comparison with control groups. Statistical data processing was performed using GraphPad Prism 9 (Insight Partners, USA).Results. The antipsychotic activity of 1-(2-diethylaminoethyl)-2-(4-methoxyphenyl)-imidazo[1,2-a] benzimidazole — RU-31 compound with 5-HT2A-antagonistic mechanism of action was evaluated. RU-31 compound (10 mg/kg, intraperitoneally (i.p.)) statistically signifi cantly reduced vertical and horizontal spontaneous locomotor activity in rats with psychotic disorder by 18.8% and 20.9%, while the atypical neuroleptic clozapine (2 mg/kg, i.p.) signifi cantly reduced these values by 41.15% and 27.67%, respectively. The 5-HT2A-receptor antagonist RU-31 increased EEG signal power in the delta range by 123.33% and decreased it in the alpha range by 41.86% in surgically operated animals (p < 0.05). Clozapine increased the EEG signal power in all studied frequency ranges: in delta — by 107.99%, theta — by 97.16%, alpha — by 41.86% and in beta — by 49.16% in animals with neonatal destruction of the ventral hippocampus (p < 0.05).Conclusion. The studied substances contributed to the correction of behavioural disturbances associated with hypermobility as well as electrophysiological changes induced by a surgical operation, while similar activity was not observed (or was observed to a lesser extent) in healthy animals.
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