A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats

Kashkin V.A.; Shekunova E.V.; Makarova M.N.; Makarov V.G.

doi:https://doi.org/10.17116/jnevro20171177159-63

Kashkin V.A.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia;
Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia

Shekunova E.V.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia;
Pavlov First State medical university, St. Petersburg, Russia

Makarova M.N.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia

Makarov V.G.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia

A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats

Authors:

Kashkin V.A., Shekunova E.V., Makarova M.N., Makarov V.G.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(7): 59‑63

DOI: 10.17116/jnevro20171177159-63

Read: 4616 times

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Kashkin VA, Shekunova EV, Makarova MN, Makarov VG. A study of combination treatment with nacom (levodopa + carbodope) and citicoline in the model of Parkinson disease in rats. S.S. Korsakov Journal of Neurology and Psychiatry. 2017;117(7):59‑63. (In Russ.)
https://doi.org/10.17116/jnevro20171177159-63

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

Close metadata

Recommended articles:

Pathomorphosis of the Parkinson’s disease against the background of DBS STN. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(2):21-27

Cognitive impairment in asthenic disorders. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(3):27-32

The effect of bilateral subthalamic nucleus deep brain stimulation on gait and balance in patients with Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(3):94-101

Neuroinflammatory and neurodegenerative aspects of Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(3):102-111

Schizophrenic spectrum disorders and Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(3):136-141

Art and creativity in Parkinson’s disease: the mysterious effects of dopamine. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):13-20

Correlation of motor symptoms and cardiovascular dysfunction in Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):59-67

Diagnosis of pathological and adaptive balance changes in Parkinson’s disease to select a rehabilitation program. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4):88-94

Sleep disorders in patients with Lewy body dementia and Parkinson’s disease. S.S. Korsakov Journal of Neurology and Psychiatry. 2025;(4-2):81-87

Potential and prospects of the astragaloside IV use for age-associated diseases prevention. Russian Journal of Preventive Medicine. 2025;(7):94-99

Abstract:

Objective. To evaluate the efficacy of the combined use of citicoline (neipilept) and levodopa/carbidopa (nakom) in the rotenone model of Parkinson’s disease in rats. Material and methods. Rotenone was administrated during 14 days in dose 2 mg/kg/day subcutaneously. The duration of treatment was 7 days, intragastrically. Alteration of locomotor behavior components, muscular rigidity in resistance to passive flexion in the ankle joint and signs of extrapyramidal disorders were assessed. Results and conclusion. Combined therapy led to the decrease in muscle rigidity (the decrease of gibbosity in resistance to passive flexion in the ankle joint). There was a decrease in oligokinesia that emerged in higher vertical and horizontal locomotor activity of experimental animals, decrease in the time of head turning during climbing down the pole and total time of climbing down the pole. The combination of drugs had a more pronounced therapeutic effect on extrapyramidal disorders compared to monotherapy.

Keywords:

Parkinson`s disease

levodopa

rotenone

citicoline

rat

Authors:

Kashkin V.A.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia;
Sechenov Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia

Shekunova E.V.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia;
Pavlov First State medical university, St. Petersburg, Russia

Makarova M.N.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia

Makarov V.G.

Scientific and Production Association «House of pharmacy», St. Petersburg, Russia

Close metadata

References:

Alexander GE. Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues in Clinical Neuroscience. 2004;6(3):259-280.
DeLong MR, Wichmann T. Circuits and circuit disorders of the basal ganglia. Archives of neurology. 2007;64(1):20-24. https://doi.org/10.1001/archneur.64.1.20
Sonsalla PK, Heikkila RE. The influence of dose and dosing interval on MPTP-induced dopaminergic neurotoxicity in mice. Eur J Pharmacol. 1986;129(3):339-345. https://doi.org/10.1016/0014-2999(86)90444-9
Kirik D, Rosenblad C, Bjorklund A. Preservation of a functional nigrostriatal dopamine pathway by GDNF in the intrastriatal 6-OHDA lesion model depends on the site of administration of the trophic factor. The European journal of neuroscience. 2000;12(11):3871-3882. https://doi.org/10.1046/j.1460-9568.2000.00274.x
Alam M, Schmidt WJ. Rotenone destroys dopaminergic neurons and induces parkinsonian symptoms in rats. Behavioural brain research. 2002;136(1):317-324. https://doi.org/10.1016/S0166-4328(02)00180-8
Cannon JR, Tapias V, Na HM, Honick AS, Drolet RE, Greenamyre JT. A highly reproducible rotenone model of Parkinson’s disease. Neurobiology of disease. 2009;34(2):279-290. https://doi.org/10.1016/j.nbd.2009.01.016
Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa, Y. Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochemical and biophysical research communications. 1989;163(3):1450-1455. https://doi.org/10.1016/0006-291x(89)91141-8
Haas RH, Nasirian F, Nakano K, Ward D, Pay M, Hill R, Shults CW. Low platelet mitochondrial complex I and complex II/III activity in early untreated Parkinson’s disease. Annals of neurology. 1995;37(6):714-722. https://doi.org/10.1002/ana.410370604
Fleming SM, Salcedo J, Fernagut PO, Rockenstein E, Masliah E, Levine MS, Chesselet MF. Early and progressive sensorimotor anomalies in mice overexpressing wild-type human alpha-synuclein. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2004;24(42):9434-9440. https://doi.org/10.1523/jneurosci.3080-04.2004
Colamartino M, Padua L, Meneghini C, Leone S, Cornetta T, Testa A, Cozzi R. Protective effects of L-dopa and carbidopa combined treatments on human catecholaminergic cells. DNA and cell biology. 2012;31(11):1572-1579. https://doi.org/10.1089/dna.2011.1546
Saligaut C, Daoust M, Chadelaud M, Moore N, Chretien P, Boismare F. Oxotremorine-induced cholinergic syndrome: modifications by levodopa and/or oral cytidine diphosphocholine. Methods and findings in experimental and clinical pharmacology. 1985;7(1):5-8.
Matteucci A, Varano M, Gaddini L, Mallozzi C, Villa, M, Pricci F, Malchiodi-Albedi F. Neuroprotective effects of citicoline in in vitro models of retinal neurodegeneration. International journal of molecular sciences. 2014;15(4):6286-6297. https://doi.org/10.3390/ijms15046286
Fleming SM, Zhu C, Fernagut PO, Mehta A, DiCarlo CD, Seaman RL, Chesselet MF. Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone. Experimental neurology. 2004;187(2):418-429. https://doi.org/10.1016/j.expneurol.2004.01.023
Mironov AN. A guide to preclinical drug research. Part one. M.: Grif and K.; 2012.
Shrestha S, Phornchirasilp S, Nakornchai S, Thisayakorn K. Quantitative Analysis of Behavior in Rotenone-Induced Parkinsonism in Rats Using Force Plate Actimeter. 2016;38(1):10.
Hiam Rushdy A. Salem, Amira Abd El-Raouf Mohamed, Eman M. Saleh, Kamal A.F. Shalaby. Influence of Hesperidin combined with Sinemet on genetical and biochemical abnormalities in rats suffering from Parkinson’s disease. Life Sci J. 2012;9(4):930-945. https://doi.org/10.7537/marslsj090412.145
Lindner MD, Plone MA, Francis JM, Emerich DF. Validation of a rodent model of Parkinson’s Disease: evidence of a therapeutic window for oral Sinemet. Brain Res Bull. 1996;39(6):367-372. https://doi.org/10.1016/0361-9230(96)00027-5
Saligaut C, Daoust M, Moore N, Boismare F. Circling behaviour in rats with unilateral lesions of the nigrostriatum induced by 6-hydroxydopamine: changes induced by oral administration of cytidine-5’-diphosphocholine. Neuropharmacology. 1987;26(9):1315-1319. https://doi.org/10.1016/0028-3908(87)90093-1
Ogawa N, Hirose Y, Ohara S, Ono T, Watanabe Y. A simple quantitative bradykinesia test in MPTP-treated mice. Research communications in chemical pathology and pharmacology. 1985;50(3):435-441.
Nagatsu T, Sawada M. L-dopa therapy for Parkinson’s disease: Past, present, and future. Parkinsonism & Related Disorders. 2009;15:3-8. https://doi.org/10.1016/s1353-8020(09)70004-5
Blessing H, Bareiss M, Zettlmeisl H, Schwarz J, Storch A. Catechol-O-methyltransferase inhibition protects against 3,4-dihydroxyphenylalanine (DOPA) toxicity in primary mesencephalic cultures: new insights into levodopa toxicity. Neurochemistry international. 2003;42(2):139-151. https://doi.org/10.1016/S0197-0186(02)00075-X
Hattori N, Wang M, Taka H, Fujimura T, Yoritaka A, Kubo S, Mochizuki H. Toxic effects of dopamine metabolism in Parkinson’s disease. Parkinsonism & Related Disorders. 2009;15:35-38. https://doi.org/10.1016/S1353-8020(09)70010-0
Eberhardt R, Birbamer G, Gerstenbrand F, Rainer E, Traegner H. Citicoline in the treatment of Parkinson’s disease. Clinical therapeutics. 1990;12(6):489-495.
Cubells JM, Hernando C. Clinical trial on the use of cytidine diphosphate choline in Parkinson’s disease. Clinical therapeutics. 1988;10(6):664-671.
Hardie RJ, Malcolm SL, Lees AJ, Stern GM, Allen JG. The pharmacokinetics of intravenous and oral levodopa in patients with Parkinson’s disease who exhibit on-off fluctuations. British journal of clinical pharmacology. 1986;22(4):429-436. https://doi.org/10.1111/j.1365-2125.1986.tb02913.x
Leppert PS, Cortese M, Fix JA. The effects of carbidopa dose and time and route of administration on systemic L-dopa levels in rats. Pharmaceutical research. 1988;5(9):587-591. https://doi.org/10.1023/A:1015946114321.
Goole J, Amighi K. Levodopa delivery systems for the treatment of Parkinson’s disease: an overview. International journal of pharmaceutics. 2009;380(1-2):1-15. https://doi.org/10.1016/j.ijpharm.2009.07.026
Agut J, Ortiz JA, Wurtman RJ. Cytidine (5’)diphosphocholine modulates dopamine K(+)-evoked release in striatum measured by microdialysis. Annals of the New York Academy of Sciences. 2000;920:332-335. https://doi.org/10.1111/j.1749-6632.2000.tb06944.x
Petkov VD, Kehayov RA, Mosharrof AH, Petkov VV, Getova D, Lazarova MB, Vaglenova J. Effects of cytidine diphosphate choline on rats with memory deficits. Arzneimittel-Forschung. 1993;43(8):822-828.