Study of the possibility of using metformin by intranasal administration for the correction of behavioral and cognitive dysfunctions of rats
Relevance. Metformin is an antidiabetic agent in the therapy of type 2 diabetes mellitus, which has a complex of pharmacological effects that may allow its use as a geroprotector and a means for the treatment of cognitive and behavioral disorders. Metformin when administered orally has low bioavaila...
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| Main Authors: | , |
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| Format: | Article |
| Language: | Russian |
| Published: |
LLC “Publisher OKI”
2025-05-01
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| Series: | Фармакокинетика и Фармакодинамика |
| Subjects: | |
| Online Access: | https://www.pharmacokinetica.ru/jour/article/view/448 |
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| Summary: | Relevance. Metformin is an antidiabetic agent in the therapy of type 2 diabetes mellitus, which has a complex of pharmacological effects that may allow its use as a geroprotector and a means for the treatment of cognitive and behavioral disorders. Metformin when administered orally has low bioavailability (50–60 %), as well as the risk of side effects, which is the rationale for studying the intranasal route of administration of metformin.Objective. To investigate the behavioral effects of metformin during intranasal administration as a rationale for the development of its intranasal dosage form.Materials and methods. The object of the study was metformin administered intranasally (i/n) to rats at a dose of 70 mg/kg. The intragastric (i/g) route of administration (70 mg/kg) was used for comparison. After 30-day i/n and i/g administration of metformin, the rats were subjected to behavioral tests: the T-Maze test, Water Maze test, Elevated Plus-Maze test (EPM), and Extrapolation Escape task (EE). The Student's t-test in Graph pad Prism 8.0.1 program was used for statistical processing.Results. When administered i/n, there was 5.6 times (p = 0.022) decrease in the latent period of arm selection (p = 0.022), and when administered i/g, there was 2.9 times (p = 0.01) decrease in the “T-maze”test compared to the control. No statistically significant result was found in the “EPM”test when applied i/n, in contrast to i/g, in which the duration of stay of rats in the OА of the maze was 3.0 times (p = 0.01) more than the control, and in the CA — 1.3 times (p = 0.01) less. In the “EE” test, i/n administration of metformin contributed to 5.1 times (p = 0.02) decrease in jump duration compared to control. In case of i/g administration metformin, the duration of the jumping period was 2.9 times shorter (p = 0.038).Conclusion. Intranasal administration of metformin can be considered as an alternative way of its use and be the basis for the development of a system of directed delivery of metformin. |
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| ISSN: | 2587-7836 2686-8830 |