Biomedical subjects
Publications and source records attributed to E A Val'dman.
Himantane introduced via a gastric tube to pregnant rats in a dose of 10, 30, 50, and 100 mg/kg produced a dose-dependent embryotoxic and teratogenic action. An analysis of the experimental results and published data suggests that the embryotoxicity of himantane can be related to its general toxic action upon the organism of pregnant female rats.
N-(Adamant-2-yl)hexamethyleneimine hydrochloride (hemantane) is a new potential antiparkinsonian drug with a complex mechanism of action. The drug exhibits the properties of a low-affinity blocker of the ion channels of NMDA receptors, increases the dopamine content in striatum, and inhibits monoamine oxidases (MAO-B). This combination of properties suggests that hemantane can also possess neuroprotector properties. In this context, the ability of hemantane to prevent from the development of MPTP neurotoxin action on the locomotor activity in mice and the EEG activity in rats has been studied. Preliminary single (and the more so, repeated over a period of 5 days) peroral administration of hemantane in a dose of 10 mg/kg significantly reduced the manifestations of MPTP-induced oligokinesia in C57BL/6 mice. Acute of subchronic (7-day) pretreatment with hemantane prevented the development of EEG changes typical of parkinsonism. The results of statistical EEG data processing showed that a systemic introduction of MPTP (30 mg/kg) on the background of hemantane pretreatment produced no reliable changes against control characteristics. Thus, hemantane is capable of protecting experimental animals from MPTP neurotoxicity.
The activity of the adamantane derivative PK-Merz and the new aminoadamantane derivative hemantane was studied by methods of electromyography and electroneuromyography in rats with a model of Parkinson syndrome induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The toxin produced an increase in the pulse conduction velocity (PCV) in the motor fibers of peripheral nerves and a decrease in the amplitude and frequency of the maximum muscle stress curve. A singe administration of both PK-Merz and hemantane produced unidirectional changes in the neuromyographic parameters and reduced the PCV down to a level in the control group. These results give ground for the clinical investigation of hemantane.
Chronic administration of a low dose of reversible monoamine oxidase (MAO) B inhibitors isatin or himantane (20 mg/kg) to mice during 21 day did not influence the enzyme activity assayed in isolated brain mitochondria. However in vivo sensitivity of brain MAO B to irreversible mechanism-based inhibitor deprenyl injected to animals right after the last administration of the reversible inhibitor sharply decreased. This suggests accumulation of these compounds (or their metabolites?) in the brain accompanied by increased protection of active site of MAO B against specific irreversible inhibitor. deprenyl. In vitro inhibition of MAO B activity in mitochondria isolated from brain of mice treated with isatin or himantane was somewhat higher than in control mitochondria. The latter suggests that long-term treatment of animals with reversible easily dissociating inhibitors may influence regulatory properties of MAO B.
Effect of the new potential antiparkinsonian drug hemantane (N-(adamant-2-yl)hexamethyleneimine hydrochloride) on the generative function and gonad morphology was studied in a group of male and female mongrel rats. The generative function was studied after peroral drug administration in a dose of 10 mg/kg (ED50) and 50 mg/kg (5 ED50): males were treated over a 60-day period of spermatogenesis, while females received the drug in the same doses over 15 days (three estrous cycles). The gonad morphology was studied after a 6-month treatment of experimental animals with hemantane in the same doses. It was established that the administration hemantane in indicated doses did not influence the generative function and gonad morphology in male and female rats.
Changes in the BDNF content in brain structures--hippocampus, hypothalamus, striatum, and frontal cortex--were determined in mice of different emotional-stress reaction phenotypes, which were subjected to emotional stress and treated by the selective anxiolytic afobazole. The changes were different in BALB/c and C57BL/6 mice. Afobazole exhibited a significant protector action against a decrease in the brain BDNF level caused by emotional stress in BALB/c mice.
The neuroprotective effect of the new selective anxiolytic afobazole was evaluated in rats with ischemic stroke produced by the occlusion of the left middle cerebral artery, with simultaneous ligation of the ipsilateral carotid artery. Afobazole exhibits a protective effect in a dose range from 0.1 to 5.0 mg/kg for the first injection delayed 24 h after operation and double daily injections over the following two days.