caa a22 4500 469079487 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00176626 doi (NATIONALLICENCE)springer-10.1007/BF00176626 Attenuation of the morphine withdrawal syndrome by inhibition of catabolism of endogenous enkephalins in the periaqueductal gray matter [Elektronische Daten] [R. Maldonado, M. Fournie-Zaluski, B. Roques] Summary: We have investigated the effects of the local administration into the periaqueductal gray matter of thiorphan, a selective inhibitor of endopeptidase 24.11 "enkephalinase”, kelatorphan, (R)-3-(N-hydroxy-carboxamido-2-benzylpropanoyl)-L-alanine, and RB 38 A, (R)-3-(N-hydroxycarboxamido-2-benzylpropanoyl)-L-phenylalanine, two almost complete inhibitors of enkephalin metabolism, on the naloxone-precipitated morphine withdrawal syndrome in rats. Local administration of these inhibitors decreased the severity of the withdrawal syndrome. Jumping, chewing, diarrhea, piloerection, salivation and hypothermia were decreased by all drugs. Lacrimation and weight loss were reduced by kelatorphah and RB 38 A whereas teeth chattering, tremor, eye twitch and rhinorrhea were decreased only by RB 38 A. The rise in plasma corticosterone levels was only slightly reduced by the three inhibitors. Wet dog shakes and ptosis remained unchanged. These results indicate that during the morphine withdrawal syndrome in rats there is a tonic or/and naloxone evoked release of opioid peptides, presumably enkephalins, into the periaqueductal gray matter and that inhibition of their degradation strongly decreases the severity of the withdrawal syndrome. Springer-Verlag, 1992 Morphine withdrawal nationallicence Periaqueductal gray matter nationallicence Enkephalin catabolism inhibitors nationallicence Kelatorphan nationallicence Thiorphan nationallicence Maldonado R. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut Fournie-Zaluski M. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut Roques B. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 466-472 0028-1298 345:4<466 1992 345 210 https://doi.org/10.1007/BF00176626 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00176626 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Maldonado R. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut NATIONALLICENCE 700 1- Fournie-Zaluski M. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut NATIONALLICENCE 700 1- Roques B. Département de Chimie Organique, U 266 INSERM, UA 498 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, F-75006, Paris, France aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 466-472 0028-1298 345:4<466 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer