Lack of physical dependence in mice after repeated systemic administration of the mixed inhibitor prodrug of enkephalin-degrading enzymes, RB101
| Autor: | Marie-Claude Fournie-Zaluski, Pascale Coric, Florence Noble, Bernard P. Roques |
|---|---|
| Přispěvatelé: | Pharmacochimie moléculaire et structurale, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 1992 |
| Předmět: |
Male
medicine.medical_specialty Enkephalin Substance-Related Disorders Phenylalanine RB-101 Physical dependence (+)-Naloxone Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Prodrugs Disulfides ComputingMilieux_MISCELLANEOUS Injections Intraventricular 030304 developmental biology Pharmacology 0303 health sciences Behavior Animal Morphine Naloxone business.industry Body Weight Prodrug [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences Substance Withdrawal Syndrome 3. Good health Endocrinology Opioid Systemic administration medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Journal of Pharmacology European Journal of Pharmacology, Elsevier, 1992, 223 (1), pp.91-96. ⟨10.1016/0014-2999(92)90822-L⟩ |
| ISSN: | 0014-2999 |
| Popis: | Development of physical dependence is observed after treatment with opioid agonists, but not after chronic i.c.v. administration of mixed inhibitors of enkephalin-degrading enzymes. The aim of this study was to investigate further this promising result of repeated administration of the systemically active mixed inhibitor prodrug RB101, N-[(R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyldithio]-1-oxopro pyl]- L-phenylalanine benzyl ester. In a comparative study, the naloxone-evoked withdrawal syndrome was quantified in mice chronically treated with i.p. administered morphine or RB101 (6 and 160 mg/kg, respectively) for 5 days, twice daily. After administration of naloxone (5 mg/kg s.c.) on the sixth day, large behavioral changes (jumps, paw shakes, wet-dog shakes, tremor, teeth chattering) and body weight losses occurred in the morphine-treated mice. In contrast, no significant behavioral signs of physical dependence, or body weight changes were observed in the RB101-treated mice. The difference between morphine and RB101 could be partially due to a very low tonic release of enkephalins in the locus coeruleus, a brain region critically involved in the development of physical dependence. These results confirm the potential of mixed inhibitors of enkephalin-degrading enzymes as new non-addictive analgesics. |
| Databáze: | OpenAIRE |
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