Antiamnestic effect of new nicotinic acid derivatives

Introduction: The search for new drugs for the prevention and treatment of vascular cognitive disorders continues to be a relevant task of pharmacology. In this regard, the aim of this work is to study the antiamnestic effect of five new nicotinic acid derivatives in comparison with the well-known drug mexidol (ethylmethylhydroxypyridine succinate) in animals. Materials and methods: The experiments were carried out on white male mice using conditioned passive avoidance reflex (CPAR). Electroconvulsive shock (ECS), scopolamine administration, and acute hypoxia in a hermetic chamber were used as amnesic effects. Testing for the safety of CPAR was performed 24 h after amnesic exposure. The new substances, reference drug mexidol, and a 0.9% sodium chloride solution (control group) were administered once intraperitoneally 60 min before mice training. Results and discussion: Three of the five new nicotinic acid derivatives, LKhT 4-19 (100 mg/kg), LKhT 6-19 (25, 50, and 100 mg/kg), and LKhT 7-19 (100 mg/kg), have antiamnestic properties on models of amnesia in mice induced by ESC, scopolamine, and acute hypoxia in a hermetic chamber. At the same time, the most efficient substance – LKhT 6-19 – exceeds the reference drug mexidol on all three models used. In addition, this compound is also more efficient than two other new compounds, LKhT 4-19 and LKhT 7-19, on the model of ESC-induced amnesia and LKhT 7-19 on the scopolamine-induced amnesia model. Conclusion: Compound LKhT 6-19 is promising for further advanced preclinical studies as a potential drug with antiamnestic activity. Graphical abstract:

ВЛИЯНИЕ ОБЕДНЕННОГО ДЕЙТЕРИЕМ ПИТЬЕВОГО РАЦИОНА НА ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫ ЖИВОТНЫХ В УСЛОВИИ ГИПОКСИИ

The effects of prolonged (42 days) addition of deuterium-depleted water into rat’s diet on the functional state of the central nervous system in normal conditions and under conditions of normobaric hypoxia with hypercapnia were studied. It was also established that the use of deuterium-depleted water both in normal conditions and after exposure to oxidative stress contributes to a significant reduction in the emotional anxiety of animals. Prolonged use of deuterium-depleted water before hypoxic exposure (amnestic effect) helps to maintain learning and memory at the control level, i.e. it has a pronounced protective antiamnestic effect. In normal conditions, deuterium-depleted water does not affect the learning ability of animals.

Correction of cognitive-mnestic dysfunction of rats after ketamine anesthesia under the influence of heteroside

Today, in medical practice, a very promising direction of development can be the expansion of the range of primary and secondary neuroprotection drugs through the use of targeted synthesis of potential neuroprotective agents with analeptic effect. This is necessary to improve anesthetic safety during surgery and to alleviate post-anesthetic intoxication after anesthesia. Therefore, the aim of our study was to compare the neuroprotective activity of original derivatives of sulfur and nitrogen-containing heterocycles (heterosides) and reference drugs, which are already known in pharmacology (cerebroprotective agent with neurotrophic action ¾ cerebrocurin and nootropic drug with neuroprotective action ¾ noopept). In the course of the research, it was found that after ketamine anesthesia, the excitability of the central nervous system increases, the anxious behavior of animals increases, while the indicators of the research work of animals in the experiment sharply deteriorate. After 2 days or more (10 days) after the transferred ketamine anesthesia, a deterioration in mnestic functions was noted in this group of animals. With the introduction of 100 mg / kg of heteroside to a group of rats after ketamine anesthesia, the indicators of anxiety behavior and excitability of animals significantly decreased, their research activity increased, a pronounced antiamnestic effect was manifested, and the ability of animals to learn was increased as well. It also turned out that in terms of the degree of influence on the indicators of the cognitive-mnestic functions of the central nervous system, heteroside statistically significantly exceeds the comparison drugs cerebrocurin and noopept, which in turn showed high efficiency in reducing anxiety of animals, and also had an antiamnestic effect, but did not affect the ability of animals to learn.

Antiamnestic effect of Phlojodicarpus sibiricus extract in a scopolamine-induced amnesia model

The present study was investigated influence of Phlojodicarpus sibiricus (Steph. ex. Spregel) K.-Pol. extract on memory in scopolamine-induced amnesia in rats using object recognition test. The rats were divided into four groups: the first group consist of rats received purified water; rats of two groups administrated scopolamine in dose 1 mg/kg and purified water intraperitoneally; rats of three and four groups introduced scopolamine and P. sibiricus extract in doses 50 and 100 mg/kg accordingly intraperitoneally. The object recognition test was performed 30 minutes after the administration of scopolamine and the P. sibiricus extract. The results of the studies showed that administration of the P. sibiricus extract in animals at doses of 50 and 100 mg/kg prevented the development of amnesia caused by the administration of scopolamine. The antiamnestic effect of P. sibiricus extract is due to the cholinergic effect of coumarins contained in the plant. (For citation: Gulyaev SM, Taraskin VV, Radnayeva LD, Nikolaev SM. Antiamnestic effect of Phlojodicarpus sibiricus extract in a scopolamine-induced amnesia model. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):53-57. doi: 10.17816/RCF15453-57).