| Autor: |
Daria S. Gorina, Anastasiya V. Lastovka, Artem D. Rogachev, Alexandra V. Podturkina, Alla V. Pavlova, Oleg V. Ardashov, Nikolai S. Li-Zhulanov, Tatyana G. Tolstikova, Konstantin P. Volcho, Nariman F. Salakhutdinov |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Molecules, Vol 29, Iss 18, p 4498 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1420-3049 |
| DOI: |
10.3390/molecules29184498 |
| Popis: |
The novel antiparkinsonian agent PA-96 is the focus of our research. PA-96 supported the survival of cultured naïve dopamine neurons, alleviated motor deficits in MPTP and haloperidol-based mice models of Parkinson’s disease, and increased the density of tyrosine hydroxylase positive neurons and dopamine concentration in the midbrain of an MPTP-damaged brain. In this work, an HPLC–MS/MS method was developed and validated, and the pharmacokinetics of the agent was investigated in mice after a single or multiple oral administration (p.o.) and intravenous injection (i.v.) at various doses. The dose proportionality was also evaluated after a single p.o. administration of three ascending doses (1, 5, and 10 mg/kg) and a single i.v. injection of two doses (1 and 10 mg/kg); also, the bioavailability was estimated. The disproportionality of pharmacokinetic parameters could be explained by the saturation of active centres of enzymes or receptors binding the substance: at low doses, part of the compound is bound, leaving a small amount circulating in blood, and rapidly metabolised and/or bound too. The bioavailability of PA-96 was c.a. 7 and 35% for the doses of 5 and 10 mg/kg, correspondingly. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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