Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures
Introduction: Parkinson’s disease (PD) is a chronic neurodegenerative disease of the central nervous system, the pathogenesis of which is associated with the death of dopaminergic neurons of the midbrain substantia nigra. The mainstay of therapy for PD is levodopa. However, in the initial stages of...
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| Language: | English |
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Belgorod National Research University
2024-12-01
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| Series: | Research Results in Pharmacology |
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| Online Access: | https://rrpharmacology.ru/index.php/journal/article/view/540 |
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| author | Vladimir N. Fedorov Mikhail K. Korsakov Anton A. Shetnev Sergey S. Petukhov Nikita N. Volkhin Vladimir P. Vdovichenko Anastasia A. Khokhlova Salavat Sh. Suleymanov |
| author_facet | Vladimir N. Fedorov Mikhail K. Korsakov Anton A. Shetnev Sergey S. Petukhov Nikita N. Volkhin Vladimir P. Vdovichenko Anastasia A. Khokhlova Salavat Sh. Suleymanov |
| author_sort | Vladimir N. Fedorov |
| collection | DOAJ |
| description | Introduction: Parkinson’s disease (PD) is a chronic neurodegenerative disease of the central nervous system, the pathogenesis of which is associated with the death of dopaminergic neurons of the midbrain substantia nigra. The mainstay of therapy for PD is levodopa. However, in the initial stages of PD or in case of levodopa intolerance, MAO B inhibitors are used. Purpose of the study was to determine antiparkinsonian activity of newly synthesized selective MAO-B inhibitors in vivo on the model of experimental parkinsonism in white mice.
Materials and Methods: Parkinsonian syndrome in mice was modeled by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). As the criteria for its evaluation, we used the determination of muscle rigidity severity by step length of mice and evaluation of oligokinesia severity and emotional and mental disturbances in the open field test. A total of 9 candidate compounds were studied, assigned with laboratory codes S1-S5, S9, S10, S14, and S15. Rasagiline was used as a comparison drug.
Results and Discussion: Of the 9 compounds used at a dosage of 2mg/kg, the degree of rigidity was significantly reduced by compounds S1, S9, and S15; locomotor activity was restored to the level reached through rasagiline only by compound S9; the decline in exploratory activity was prevented only by S9 and to some extent by S5.
Conclusion: Only compound S9 having benzenesulfonamide chemotype showed significant therapeutic potential in a model of experimental parkinsonism and only in relation to it additional studies can be planned. |
| format | Article |
| id | doaj-art-d5548bc29c78452ca1ffc00bbf689970 |
| institution | Kabale University |
| issn | 2658-381X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj-art-d5548bc29c78452ca1ffc00bbf6899702025-01-08T13:23:22ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2024-12-0110412913510.18413/rrpharmacology.10.540Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structuresVladimir N. Fedorov0https://orcid.org/0009-0003-1296-1861Mikhail K. Korsakov1https://orcid.org/0000-0003-0913-2571Anton A. Shetnev2https://orcid.org/0000-0002-4389-461XSergey S. Petukhov3https://orcid.org/0009-0007-8435-7689Nikita N. Volkhin4https://orcid.org/0000-0002-4275-9037Vladimir P. Vdovichenko5https://orcid.org/0009-0009-6739-6154Anastasia A. Khokhlova6https://orcid.org/0009-0007-8258-7085Salavat Sh. Suleymanov7https://orcid.org/0000-0002-3176-2716Yaroslavl State Pedagogical University named after K.D. UshinskyYaroslavl State Pedagogical University named after K.D. UshinskyYaroslavl State Pedagogical University named after K.D. UshinskyYaroslavl State Pedagogical University named after K.D. UshinskyYaroslavl State Pedagogical University named after K.D. UshinskyGrodno State Medical UniversityRussian Medical UniversitySaiko Russian-Japanese Medical CenterIntroduction: Parkinson’s disease (PD) is a chronic neurodegenerative disease of the central nervous system, the pathogenesis of which is associated with the death of dopaminergic neurons of the midbrain substantia nigra. The mainstay of therapy for PD is levodopa. However, in the initial stages of PD or in case of levodopa intolerance, MAO B inhibitors are used. Purpose of the study was to determine antiparkinsonian activity of newly synthesized selective MAO-B inhibitors in vivo on the model of experimental parkinsonism in white mice. Materials and Methods: Parkinsonian syndrome in mice was modeled by systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). As the criteria for its evaluation, we used the determination of muscle rigidity severity by step length of mice and evaluation of oligokinesia severity and emotional and mental disturbances in the open field test. A total of 9 candidate compounds were studied, assigned with laboratory codes S1-S5, S9, S10, S14, and S15. Rasagiline was used as a comparison drug. Results and Discussion: Of the 9 compounds used at a dosage of 2mg/kg, the degree of rigidity was significantly reduced by compounds S1, S9, and S15; locomotor activity was restored to the level reached through rasagiline only by compound S9; the decline in exploratory activity was prevented only by S9 and to some extent by S5. Conclusion: Only compound S9 having benzenesulfonamide chemotype showed significant therapeutic potential in a model of experimental parkinsonism and only in relation to it additional studies can be planned.https://rrpharmacology.ru/index.php/journal/article/view/540parkinson’s diseasemao-b inhibitorsexperimental parkinsonismbenzenesulfonamide derivative |
| spellingShingle | Vladimir N. Fedorov Mikhail K. Korsakov Anton A. Shetnev Sergey S. Petukhov Nikita N. Volkhin Vladimir P. Vdovichenko Anastasia A. Khokhlova Salavat Sh. Suleymanov Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures Research Results in Pharmacology parkinson’s disease mao-b inhibitors experimental parkinsonism benzenesulfonamide derivative |
| title | Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures |
| title_full | Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures |
| title_fullStr | Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures |
| title_full_unstemmed | Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures |
| title_short | Antiparkinsonian activity of selective MAO-B inhibitors of different chemical structures |
| title_sort | antiparkinsonian activity of selective mao b inhibitors of different chemical structures |
| topic | parkinson’s disease mao-b inhibitors experimental parkinsonism benzenesulfonamide derivative |
| url | https://rrpharmacology.ru/index.php/journal/article/view/540 |
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