Effect of Original Peptide Derivatives of Galantamine on Passive Avoidance in Mice
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Bulletin of Experimental Biology and Medicine, Vol. 170, No. 2, December, 2020
PHARMACOLOGY AND TOXICOLOGY Effect of Original Peptide Derivatives of Galantamine on Passive Avoidance in Mice I. I. Kostadinova1, N. D. Danchev1, L. T. Vezenkov2, D. S. Tsekova2, and V. V. Rozhanets3
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 165-167, August, 2020 Original article submitted April 30, 2020 The effect of original peptide derivatives of galantamine on scopolamine-induced memory impairment in mice was assessed using the passive avoidance test over 12 days. It was found that some galantamine derivatives administered in a dose of 1/20LD50 improved the memory in experimental mice, especially on days 5-12 of the experiment. Key Words: Alzheimer’s disease; peptide derivatives of galantamine; passive avoidance; galantamine; scopolamine Alzheimer‘s disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. One of the therapeutic strategies in the treatment of cognitive symptoms of AD is aimed at improvement of activity of the acetylcholinergic system of the brain [2]. Only 4 drugs are approved for the symptomatic treatment of AD: acetylcholinesterase inhibitors rivastigmine, donepezil, and galantamine, and NMDA receptor antagonist memantine. However, low efficacy and numerous side effects of approved drugs necessitate the search for new therapeutic approaches for the development of more effective drugs for successful treatment of AD. Here we studied the effects of original peptide derivatives of galantamine on learning and memory in mice with scopolamine-induced amnesia. Department of Pharmacology, Pharmacotherapy, and Toxicology, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria; 2 Department of Organic Chemistry, University of Chemical Techno logy and Metallurgy, Sofia, Bulgaria; 3Laboratory of Analytical Toxicology, National Scientific Centre of Narcology — Affiliated Branch of V. P. Serbsky National Medical Research Centre of Psychiatry and Narcology, Ministry of Health of the Russian Federation, Moscow, Russia. Address for correspondence: [email protected]. I. I. Kostadinova 1
MATERIALS AND METHODS The experiment was conducted on 64 male mice of line H with body weight 25-32 g. All experiments were approved by the Institutional Animal Care Committee at the Medical University of Sofia. The animals were divided into 7 groups (8 mice per group). All tested peptide derivatives (Table 1) and galantamine were administered intraperitoneally in a dose of 1/20LD50 (75 mg/kg for 21LD and 36D; 50 mg/kg for 43LD, 44LD, and 46LD; 0.5 mg/kg for galantamine). First, peptide derivatives were homo genized in 1-2 drops DMSO and then sterile saline was added. Scopolamine hydrobromide trihydrate (3 mg/kg, Sigma-Aldrich) and galantamine hydrobromide (0.5 mg/kg, Sigma-Aldrich) were also dissolved in sterile saline. Mice of the control group received intraperitoneal injection of the vehicle. Learning and memory of experimental mice
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