Insomnia model selection for comparative evaluation of melatonin-based preparations

N.V. Demakova1, ORCID 0000-0002-2145-9289, 
M.A. Korotyhina1,
ORCID 0000-0002-2368-3268
Yu.I. Sysoev1–3, ORCID 0000-0003-4199-5318
A.V. Karshin4, ORCID 0000-0001-8145-9603
N.A. Anisimova1, ORCID 0000-0002-2620-2976
D.Yu. Ivkin1, ORCID 0000-0001-9273-6864
1Saint Petersburg State Chemical Pharmaceutical University of the Ministry of Health Care of Russia,
197376, Russian Federation, Saint Petersburg, Professora Popova str., 14;
2Institute of Translational Biomedicine, Saint Petersburg State University,
199034, Russian Federation, Saint Petersburg, Universitetskaya emb., 7–9;
3Pavlov Institute of Physiology, Russian Academy of Sciences (RAS),
199034, Russian Federation, Saint Petersburg , Makarova emb., 6;
4OOO «Farmamed»,194292, Russian Federation, Saint Petersburg, Domostroitelnaya st., 16, lit. E
E-mail: demakova.natalya@pharminnotech.com

Abstract

Currently insomnia is prevalent among 30–35% of population. As it stands now the pharmaceutical market for insomnia drugs is practically not replenished, and therefore, it is urgent to create new, more effective and / or safer drugs.

The aim of the presented work is to select and test the optimal insomnia model for a comparative assessment of the effectiveness of melatonin preparations.

A number of existing Russian and foreign models of insomnia and methods of its study were assessed, including the use of such a database of medical and biological publications as PubMed. The considered models were divided into three large blocks: models associated with stress factors, pharmacological models and genetic ones.  Animals such as rabbits, rats, mice, Danio rerio and Drosophila sp. were used as test systems for studies on models of insomnia from the analyzed literature sources. As the most suitable for the study of the comparative pharmacodynamics of a new drug based on melatonin and herbal components in terms of the severity of the hypnotic effect, rodent cage change insomnia model was chosen. Its essence boils down to changing the usual cage in sexually mature males to a cage with stale bedding containing an olfactory trace of another gender-identical animal, which acts as a stress factor in the form of expectation of aggression and allows creating the necessary conditions for conducting an experiment.

The results of a study of a melatonin preparation with a phytocomplex containing extracts of raw materials of Valeriana officinalis, Leonurus cardiaca, Crataegus sanguinea, Mentha piperita (+ oleum Menthae piperitae) indicates a significant improvement in the ratio of the theta and delta rhythm indices of animals and the alpha rhythm index, which are close to the values of the control group animals. On the basis of the EEG study, it can be concluded that the tested combination drug is more effective in comparison with the reference melatonin. Rodent cage change insomnia model is an effective and easily reproducible model which can be used not only for comparative assessment of melatonin preparations efficacy, but also for other pharmacological agents for the treatment of insomnia.

Full text avaliable in Russain only 

Author’s Contribution

M.A. Korotyhina – carried out the experiment, discussed the results, worked with literature sources, wrote the manuscript, corrected the text in accordance with the requirements of the journal
N.V. Demakova – carried out the experiment, discussed the results, worked with literature sources, wrote the manuscript, corrected the text in accordance with the requirements of the journal
Yu.I. Sysoev – carried out the experiment, performed ECOG electrode implantation, analysed the data, discussed the results, wrote the manuscript
A.V. Karshin – provided the laboratory with tested substance of melatonin + phytocomplex, confirmed the experiment design, approved the final version of the article for publication
N.A. Anisimova – literature sources analysis
D.Yu. Ivkin – designed the experiment, summarized the material, wrote the manuscript, approved the final version of the article for publication

Acknowledgements

The study was performed without external funding

 

Conflict of interest

The authors declare no conflicts of interest.

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