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

Valery E. Gmiro , Sergey E. Serdyuk , Petr D. Shabanov

Psychopharmacology & biological narcology ›› 2025, Vol. 16 ›› Issue (1) : 5 -10.

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Psychopharmacology & biological narcology ›› 2025, Vol. 16 ›› Issue (1) : 5 -10. DOI: 10.17816/phbn653995
Neuropsychopharmacology
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Comparison of the antiparkinsonian activity of N-decyltropine (IEM-1556) and levodopa in rats with rotenone-induced parkinsonism

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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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Valery E. Gmiro, Sergey E. Serdyuk, Petr D. Shabanov. Comparison of the antiparkinsonian activity of N-decyltropine (IEM-1556) and levodopa in rats with rotenone-induced parkinsonism. Psychopharmacology & biological narcology, 2025, 16(1): 5-10 DOI:10.17816/phbn653995

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References

[1]

Gmiro VE, Serdyuk SE. Сomparative study of analgesic effect of n-decyltropine (IEM-1556), adenosine and mecamylamine. Russian Journal of Physiology. 2017;103(10):1106–1113. EDN: ZIXHBP

[2]

Grigoryan GA, Bazyan AS. Experimental models of Parkinson’s disease in animals Advances in Physiological Sciences. 2007;38(4):80–88. (In Russ.) EDN: HFULAT

[3]

Abdurasulova IN, Matsulevich АV, Serdyuk SE, et al. Comparative study of the influence of IEM-1556 and glatiramer acetate (Copaxon) on the severity of neurologic disorders and the duration of experimental allergic encephalomielitis in the rats. J Multiple Sclerosis. 2018;5(1):1–3. doi: 10.4172/2376-0389.1000217

[4]

Alam M, Schmidt WJ. L-DOPA reverses the hypokinetic behaviour and rigidity in rotenone-treated rats. Behav Brain Res. 2004;153(2):439–446. doi: 10.1016/j.bbr.2003.12.021

[5]

Cannon JR, Tapias V, Na HM, et al. A highly reproducible rotenone model of Parkinson’s disease. Neurobiol Dis. 2009;34(2):279–290. doi: 10.1016/j.nbd.2009.01.016

[6]

Fleming SM, Zhu C, Fernagut PO, et al. Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Exp Neurol. 2004;187(2):418–429. doi: 10.1016/j.expneurol.2004.01.023

[7]

Gmiro VE, Serdyuk SE. New innovative drug for the treatment of Parkinson’s disease, epilepsy and chronic pain, with a combined n-Cholinolitic, Adenosine-releasing and vagal-stimulating activity. J Pharm Drug Deliv Res. 2016;5(4S):81

[8]

Lin CH, Huang JY, Ching CH, et al. Melatonin reduces the neuronal loss, downregulation of dopamine transporter, and upregulation of D2 receptor in rotenone-induced parkinsonian rats. J Pineal Res. 2008;44(2):205–213. doi: 10.1111/j.1600-079X.2007.00510.x

[9]

Mercuri NB, Bernardi G. The ‘magic’ of L-dopa: why is it the gold standard Parkinson’s disease therapy? Trends Pharmacol Sci. 2005;26(7):341–344. doi: 10.1016/j.tips.2005.05.002

[10]

Pan-Montojo F, Anichtchik O, Dening Y, et al. Progression of Parkinson’s disease pathology is reproduced by intragastric administration of rotenone in mice. PLoS One. 2010;5(1):e8762. doi: 10.1371/journal.pone.0008762

[11]

Pan-Montojo FJ, Funk RH. Oral administration of rotenone using a gavage and image analysis of alpha-synuclein inclusions in the enteric nervous system. J Vis Exp. 2010;(44):2123. doi: 10.3791/2123

[12]

Phillips RJ, Walter GC, Wilder SL, et al. Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: autonomic pathway implicated in Parkinson’s disease? Neuroscience. 2008;153(3):733–750. doi: 10.1016/j.neuroscience.2008.02.074

[13]

Rascol O, Lozano A, Stern M, et al. Milestones in Parkinson’s disease therapeutics. Mov Disord. 2011;26(6):1072–1082. doi: 10.1002/mds.23714

[14]

Wu YN, Johnson SW. Dopamine oxidation facilitates rotenone-dependent potentiation of N-methyl-D-aspartate currents in rat substantia nigra dopamine neurons. Neuroscience. 2011;195:138–144. doi: 10.1016/j.neuroscience.2011.08.041

[15]

Yang Y, Liu X, Ding JH, et al. Effects of iptakalim on rotenone-induced cytotoxicity and dopamine release from PC12 cells. Neurosci Lett. 2004;366(1):53–57. doi: 10.1016/j.neulet.2004.05.009

Funding

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

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