title: Antinociceptive effects of the enkephalinase inhibitor, SCH 34826, in the snail, Cepaea nemoralis.
abstract: In vertebrates the effects of endogenous opioid peptides are limited by proteolytic enzymes such as endopeptidase 24.11 (enkephalinase), which cleaves the Gly-Phe bonds in both methionine- and leucine-enkephalin. SCH 34826 ((S)-N-[n-[1-[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine-B-alanine) is a potent, highly specific, enkephalinase inhibitor that has marked analgesic effects in mammals. The present study examined the effects of SCH 34826 on opioid-mediated aversive thermal (nociceptive) response of an invertebrate, the land snail, Cepaea nemoralis. SCH 34828 had significant, dose-related antinociceptive effects in Cepaea that were reduced by naloxone and completely blocked by the specific data opiate antagonist, ICI-174,864, and only weakly affected by the specific kappa opiate antagonist nor-binaltrophimine. These findings with SCH 34826 suggest that an enkephalinase similar to that in vertebrates is present and involved in the mediation of opioid (enkephalin) activity in the snail, Cepaea.
authors.affiliation: Department of Psychology, University of British Columbia, Vancouver, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Saksida
authors.forename: L A
authors.initials: LA
authors.lastname: Galea
authors.forename: M
authors.initials: M
authors.lastname: Kavaliers
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004148:Dioxolanes / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D015260:Neprilysin / Q000037:antagonists & inhibitors*; D010146:Pain / Q000503:physiopathology; D012908:Snails / Q000502:physiology*
chemical_list: D000700:Analgesics; D004148:Dioxolanes; D004151:Dipeptides; D009292:Narcotic Antagonists; C056319:Sch 34826; D009270:Naloxone; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine; D015260:Neprilysin