Semicarbazide Substitution Enhances Enkephalins Resistance to Ace Induced Hydrolysis |
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Authors: | Zahra Rezaee Armin Arabanian Saeed Balalaie Abolhassan Ahmadiani Sanaz Nasoohi |
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Affiliation: | 1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, P.O. Box 19839-63113, Tehran, Iran 2. Peptide Chemistry Research Center, K.N. Toosi University of Technology, P.O. Box 15875-4416, Tehran, Iran 3. Department of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Golestan, P.O. Box 6287, Ahvaz, Iran
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Abstract: | In our previous study on [Met5]-enkephalin analogues, [Met5]-enkephalin semicarbazide was found as a new enkephalin amide that produces antinociception even in ACE (Angiotensin Converting Enzyme) exposure in vivo. In the present work we examined the corresponding [Leu5]-enkephalin derivatives to confirm the influence of semicarbazide substitution. To prevent the enkephalins biodegradation animals were pretreated with a mixture of peptidase inhibitors. As assessed by tail-flick test no significant difference was detected between the produced antinociception by the [Leu5]-enkephalin derivatives. Based on our results both semicarbazide and ethylamide groups could preserve the provided analgesia after captopril (ACE inhibitor) omission from the peptidase inhibitors mixture. This work confirms that semicarbazide substitution on enkephalins yields ACE resistance antinociceptive peptides, nevertheless it may necessarily not enhance the peptides analgesic potencies. |
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