Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms
This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide – cyclic...
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my.upm.eprints.296822015-11-11T07:07:55Z http://psasir.upm.edu.my/id/eprint/29682/ Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms Zakaria, Zainul Amiruddin Sani, Mohammed Hijaz Mohammat, Mohammed Fazli Mansor, Nurul Shulehaf Shaameri, Zurina Teh, Lay Kek Salleh, Mohd. Zaki Hamzah, Ahmad Sazali This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide – cyclic guanosine monophosphate (NO/cGMP) systems in modulating the observed antinociception. ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally to mice 60 mins prior to exposure to various antinociceptive assays. From the results obtained, ASH21374 exhibited significant (P< 0.05) antinociceptive activity in the abdominal constriction, hot-plate, and formalin tests that was comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively. ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre-treatment with 5 mg/kg naloxone significantly (P< 0.05) inhibited the activity in all assays, while pretreatment with 10 mg/k-funaltraxamine, 1 mg/kg naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P< 0.05) reversed the activity in the abdominal constriction test. L-Arginine,NG-nitro-L-arginine methyl esters (L-NAME), methylene blue, and their combinations, failed to inhibit the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated antinociceptive activities on the peripheral and central nervous systems, mediated through the activation of opioid receptors, inhibition of the glutamatergic system, and attenuation of vanilloid-mediated nociceptive transmission. Further studies have been planned to determine the pharmacological potential of ASH21374. NRC Research Press 2013-12 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/29682/1/Antinociceptive%20activity%20of%20a%20synthetic%20oxopyrrolidine.pdf Zakaria, Zainul Amiruddin and Sani, Mohammed Hijaz and Mohammat, Mohammed Fazli and Mansor, Nurul Shulehaf and Shaameri, Zurina and Teh, Lay Kek and Salleh, Mohd. Zaki and Hamzah, Ahmad Sazali (2013) Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms. Canadian Journal of Physiology and Pharmacology , 91 (12). pp. 1143-1153. ISSN 0008-4212; ESSN: 1205-7541 http://www.nrcresearchpress.com/doi/abs/10.1139/cjpp-2013-0099?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#.VV7J5vmqqko 10.1139/cjpp-2013-0099 |
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This study was carried out to determine the antinociceptive activity of a novel synthetic oxopyrrolidine-based compound, (2R,3R,4S)-ethyl 4-hydroxy-1,2-dimethyl-5-oxopyrrolidine-3-carboxylate (ASH21374), and to elucidate the involvement of the opioid, vanilloid, glutamate, and nitric oxide – cyclic guanosine monophosphate (NO/cGMP) systems in modulating the observed antinociception. ASH21374, in the doses of 2, 10, and 100 mg/kg body mass, was administered orally to mice 60 mins prior to exposure to various antinociceptive assays. From the results obtained, ASH21374 exhibited significant (P< 0.05)
antinociceptive activity in the abdominal constriction, hot-plate, and formalin tests that was comparable with 100 mg/kg acetylsalicylic acid or 5 mg/kg morphine, respectively. ASH21374 also attenuated capsaicin- and glutamate-induced paw licking. Pre-treatment with 5 mg/kg naloxone significantly (P< 0.05) inhibited the activity in all assays, while pretreatment with 10 mg/k-funaltraxamine, 1 mg/kg naltrindole, or 1 mg/kg nor-binaltorphimine significantly (P< 0.05) reversed the activity in the
abdominal constriction test. L-Arginine,NG-nitro-L-arginine methyl esters (L-NAME), methylene blue, and their combinations, failed to inhibit the ASH21374 antinociceptive activity. In conclusion, ASH21374 demonstrated antinociceptive activities on the
peripheral and central nervous systems, mediated through the activation of opioid receptors, inhibition of the glutamatergic system, and attenuation of vanilloid-mediated nociceptive transmission. Further studies have been planned to determine the pharmacological potential of ASH21374. |
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Article |
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Zakaria, Zainul Amiruddin Sani, Mohammed Hijaz Mohammat, Mohammed Fazli Mansor, Nurul Shulehaf Shaameri, Zurina Teh, Lay Kek Salleh, Mohd. Zaki Hamzah, Ahmad Sazali |
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Zakaria, Zainul Amiruddin Sani, Mohammed Hijaz Mohammat, Mohammed Fazli Mansor, Nurul Shulehaf Shaameri, Zurina Teh, Lay Kek Salleh, Mohd. Zaki Hamzah, Ahmad Sazali Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
author_facet |
Zakaria, Zainul Amiruddin Sani, Mohammed Hijaz Mohammat, Mohammed Fazli Mansor, Nurul Shulehaf Shaameri, Zurina Teh, Lay Kek Salleh, Mohd. Zaki Hamzah, Ahmad Sazali |
author_sort |
Zakaria, Zainul Amiruddin |
title |
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
title_short |
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
title_full |
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
title_fullStr |
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
title_full_unstemmed |
Antinociceptive activity of a synthetic oxopyrrolidine-based compound, ASH21374, and determination of its possible mechanisms |
title_sort |
antinociceptive activity of a synthetic oxopyrrolidine-based compound, ash21374, and determination of its possible mechanisms |
publisher |
NRC Research Press |
publishDate |
2013 |
url |
http://psasir.upm.edu.my/id/eprint/29682/1/Antinociceptive%20activity%20of%20a%20synthetic%20oxopyrrolidine.pdf http://psasir.upm.edu.my/id/eprint/29682/ http://www.nrcresearchpress.com/doi/abs/10.1139/cjpp-2013-0099?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&#.VV7J5vmqqko |
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1643829833439903744 |
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13.188404 |