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The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice
- Source :
- Nature. 288:286-288
- Publication Year :
- 1980
- Publisher :
- Springer Science and Business Media LLC, 1980.
-
Abstract
- There is both theoretical and therapeutic interest in establishing whether the signals conveyed by the enkephalins are turned off under the action of a specific peptidase which might, in this case, represent a target for a new class of psychoactive agents. Enkephalinase, a dipeptidyl carboxypeptidase cleaving the Gly3-Phe4 bond of enkephalins and distinct fropm angiotensin coverting enzyme (ACE), might be selectively involved in enkephalinergic transmission. It is a membrane-bound enzyme whose localization in the vicinity of opiate receptors in the central nervous system is suggested by parallel regional and subcellular distributions as well as by the effects of lesions. Such a role is further supported by the ontogenetic development of enkephalinase, its substrate specificity accounting for the increased biological activity of several enkephalin analogues and its adaptive increase following chronic treatment with morphine. To investigate the functional role of this enzyme further, we have designed a potent and specific enkephalinase inhibitor. We report here that this compound, thiorphan [(DL-3-mercapto-2-benzylpropanoyl)-glycine; patent no. 8008601] protects the enkephalins from the action of enkephalinase in vitro in nanomolar concentration and in vivo after either intracerebroventricular or systemic administration. In addition, thiorphan itself displays antinociceptive activity which is blocked by naloxone, an antagonist of opiate receptors.
- Subjects :
- Thiorphan
Enkephalin
RB-101
(+)-Naloxone
Pharmacology
Mice
chemistry.chemical_compound
medicine
Animals
Enkephalinase inhibitor
Protease Inhibitors
Binding Sites
Multidisciplinary
Dose-Response Relationship, Drug
Tiopronin
Nociceptors
Drug Synergism
Enkephalinase
Biological activity
Enkephalins
Amino Acids, Sulfur
chemistry
Neprilysin
Endorphins
Analgesia
Kelatorphan
medicine.drug
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....6c4fc8b47afdb8b4ab07094d10f9fd00