Comparison of the antiparkinsonian activity of N-decyltropine (IEM-1556) and levodopa in rats with rotenone-induced parkinsonism

Abstract

BACKGROUND: Previously, we published a hypothesis regarding the possible role of adenosine and vagal afferents in the mechanism of the antiparkinsonian action of N-decyltropine (IEM-1556). It lies in the ability of IEM-1556 to stimulate gastric vagal afferents as a key link in the this mechanism.

AIM: This study is to compare the antiparkinsonian activity of IEM-1556 with the reference antiparkinsonian agent (levodopa) during their chronic oral administration in a prophylactic regimen to rats with rotenone-induced parkinsonism.

METHODS: The antiparkinsonian effect of IEM-1556 (3 and 10 mg/kg), as well as the reference agent levodopa (10 and 20 mg/kg), in rats with rotenone-induced parkinsonism was assessed based on the elimination of catalepsy and oligokinesia.

RESULTS: Oral administration of N-decyltropine (IEM-1556) at a dose of 10 mg/kg significantly exceeds the antiparkinsonian activity of levodopa at a dose of 20 mg/kg, being three times more effective in reducing the number of rats with severe oligokinesia. Additionally, unlike levodopa, IEM-1556 completely eliminates severe catalepsy in rats with rotenone-induced parkinsonism. IEM-1556 appears to be a safer agent compared with levodopa, as it prevents rat mortality throughout the experiment, whereas levodopa increases mortality by the end of the study. Preliminary anesthesia of the gastric mucosa with 1% lidocaine almost completely abolishes the antiparkinsonian activity of IEM-1556 at a dose of 10 mg/kg, while not affecting the antiparkinsonian activity of levodopa at a dose of 20 mg/kg.

CONCLUSIONS: This suggests that stimulation of vagal afferents in the stomach may underlie the antiparkinsonian effect of IEM-1556 but not levodopa. IEM-1556 may be considered a potential alternative to levodopa in patients with parkinsonism resistant to levodopa therapy.Oral administration of N-decyltropine (IEM-1556) at a dose of 10 mg/kg significantly exceeds the antiparkinsonian activity of levodopa at a dose of 20 mg/kg, being three times more effective in reducing the number of rats with severe oligokinesia. Additionally, unlike levodopa, IEM-1556 completely eliminates severe catalepsy in rats with rotenone-induced parkinsonism. IEM-1556 appears to be a safer agent compared with levodopa, as it prevents rat mortality throughout the experiment, whereas levodopa increases mortality by the end of the study. Preliminary anesthesia of the gastric mucosa with 1% lidocaine almost completely abolishes the antiparkinsonian activity of IEM-1556 at a dose of 10 mg/kg, while not affecting the antiparkinsonian activity of levodopa at a dose of 20 mg/kg. This suggests that stimulation of vagal afferents in the stomach may underlie the antiparkinsonian effect of IEM-1556 but not levodopa. IEM-1556 may be considered a potential alternative to levodopa in patients with parkinsonism resistant to levodopa therapy.

Keywords

parkinsonism / rotenone / levodopa / N-decyltropine / IEM-1556

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Funding

Министерство науки и высшего образования РФMinistry of Science and Higher Education of the Russian Federation(FGWG-2025-0020)

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