{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T20:42:18Z","timestamp":1778877738393,"version":"3.51.4"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Pharmacokinetic characteristics as well as cognitive-enhancing nootropic activity of latrepirdine (Dimebon<jats:sup>\u00ae<\/jats:sup>) in relationship with its polymorphic forms have been studied in SD and Wistar rats.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The pharmacokinetics of six polymorphs (A, B, C, D, E, F) of latrepirdine were studied in male SD rats after 7\u00a0days of oral administration in corn oil at a dose of 10\u00a0mg\/kg once a day. Blood and brain samples were taken on the 7th day of administration at 15\u00a0min, 30\u00a0min, 60\u00a0min and 120\u00a0min after administration and analyzed for latrepirdine content by LC-MS. The cognitive-enhancing nootropic effect was studied in male and female Wistar rats after 9\u00a0days of oral administration in corn oil at a dose of 10\u00a0mg\/kg, after prior administration of scopolamine, an agent that causes memory impairment similar to that in Alzheimer\u2019s disease. The animals\u2019 cognitive function was studied in the passive avoidance test.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> When studying the pharmacokinetics, the highest bioavailability both in the blood and in the brain was demonstrated by polymorph E, whose AUC was the highest relative to other polymorphs. In the study of the cognitive-enhancing nootropic effect, polymorph E also showed the highest activity, whose values of the latent period of entering the dark chamber did not differ from control animals, and differed from other polymorphs.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Thus, the crystal structure has been shown to play a key role in the bioavailability and efficacy of latrepirdine, and polymorph E has also been shown to be a promising drug for the treatment of neurodegenerative diseases associated with memory impairment, such as Alzheimer\u2019s disease.<\/jats:p>","DOI":"10.3389\/fphar.2023.1091858","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T05:01:25Z","timestamp":1677042085000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Differences in bioavailability and cognitive-enhancing activity exerted by different crystal polymorphs of latrepirdine (Dimebon\u00ae)"],"prefix":"10.3389","volume":"14","author":[{"given":"Boris I.","family":"Gorin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena A.","family":"Tukhovskaya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alina M.","family":"Ismailova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gulsara A.","family":"Slashcheva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oksana A.","family":"Lenina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantin A.","family":"Petrov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilya V.","family":"Kazeev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arkady N.","family":"Murashev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1111\/j.1471-4159.1992.tb09752.x","article-title":"Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer\u2019s and Parkinson\u2019s diseases","volume":"58","author":"Aubert","year":"1992","journal-title":"J. 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