Makarenko O. V., Kryvoruchko T. M.

ANTIPARKINSONIAN PROFILE OF AMANTADINE AND GLYCINE IN RATS UNDER EXPERIMENTAL MPTPPARKINSON’S DISEASE


About the author:

Makarenko O. V., Kryvoruchko T. M.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

This work is a fragment of the research work of the Department of Pharmacology and Clinical Pharmacology at the SE “Dnipropetrovsk Medical Academy of the Ministry of Health of Ukraine” on the topic: “Systemic pharmacology of nonopioid analgesics and drugs for medical protection of the brain in conditions of pathological conditions” (SR № 0114U000935). It is known that Parkinson’s disease, which is also defined as tremulous paralysis, is a prolonged progressive condition that is accompanied by impaired motor function and neuropsychological state of the patient. Аt the initial stages of the Parkinson’s disease the NMDA-receptor inhibitor Amantadine, due to blockade of glutamate transmission, reduces the over-stimulating effect of cortical glutamate neurons on neostriatum that develops against the backdrop of insufficiency of dopamine. However, in addition to traditionally known motor disorders, the clinical picture of the Parkinson’s disease includes various non-muscular disorders – dyssomnia, sensory, neuro-psychic (cognitive, emotional-affective, behavioral) and vegetative-visceral changes. In previous works, we analysed the possibilities of using Glycine in conditions of experimental Parkinsonism (catalepsy and tremor states), taking into account the basic amantadine therapy, where it was established that the optimal Amantadine and Glycine dose ratio was Amantadine 50 mg/kg + Glycine 200 mg/kg, which is became the further object of our study. Therefore, the objective of this work was to evaluate the manifestations of catalepsy, rigidity and tremor in intra gastric administration of Glycine and Glycine in combination with Amantadine in the experimental mixed form of Parkinsonism caused by neurotoxin MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine). It was established that after 5-days administration indicated drugs (A, G200, and A + G200), the behaviour of animals in the «open field» test was characterized as active with a distinct experimental and emotional state. It was shown that under conditions of intraperitoneal administration of neurotoxin MPTP (30 mg/kg) there were changes of motor activity by type of hypokinesia. The administration of Amantadine and Amantadine in combination with Glycine contributed to the reduction of the number of crossed squares to almost the baseline. However, the emotional and research activity in these groups remained weakened: the number of visits to the mink was recorded at 1.9 (p≤0.05) and 1.96 (p≤0.05) times smaller than the baseline. In the evaluation of antiparkinsonological phenomenology, it has been found that in the control group rigidity (slouch state) was observed in 100% of animals with an estimate of 1.89 points (at the maximum possible –2 points). However, with 5-day administration of Amantadine and Amantadine in combination with Glycine, the number of rats in the state of slouch was reduced: rigidity was observed in 62.5% and 37.5% of rats of these groups with a score of 0.5 and 0.31, respectively. A similar picture is observed in evaluating the manifestations of tremor: against the background of the basic antiparkinsonal therapy Amantadine and Amantadine in combination with Glycine, the manifestations of tremor were recorded in 75% of animals in each group, with a score of 2.8 times the intensity on the scale (p≤0.05) and at 2.9 times (p≤0.05) lower compared to control group (2.81±0.23 points). Thus, in conditions of MPTP-induced parkinsonism, there is a sufficient anti-parkinsonian effect of Amantadine + Glycine in a dose of 200 mg/kg.

Tags:

Glycine, Amantadine, antiparkinson action, MPTP-Parkinsonism

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Publication of the article:

«Bulletin of problems biology and medicine» Issue 1 Part 1 (142), 2018 year, 144-147 pages, index UDK 616.858

DOI: