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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1988-7-29
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pubmed:abstractText |
SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine] was synthesized as a p.o. active prodrug enkephalinase inhibitor. In vivo, it is de-esterified to SCH 32615 (N-[L-(-1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), the active constituent. In vitro, the Ki for SCH 32615 to block the degradation of Met5-enkephalin by isolated enkephalinase is 19.5 +/- 0.9 nM. In contrast, SCH 32615 did not inhibit aminopeptidase or diaminopeptidase III degradation of Met5-enkephalin up to 10 microM and did not affect angiotensin converting enzyme up to 10 microM. In vivo, p.o. administered SCH 34826 potentiated the analgesic effects of D-Ala2-Met5-enkephalinamide in mice (ED50 = 5.3 mg/kg p.o.) and rats [minimal effective dose (MED) = 1 mg/kg p.o.]; SCH 32615 had no effect up to 30 mg/kg p.o., but was active parenterally (ED50 in mice = 1.4 ng/kg sc). Direct, naloxone-reversible analgesic effects of SCH 34826 were demonstrated in the mouse low temperature hot-plate test (MED = 30 mg/kg p.o.), the mouse acetic acid-induced writhing test (MED = 30 mg/kg p.o.), the rat stress-induced analgesia test (MED = 10 mg/kg p.o.) and the modified rat yeast-paw test (MED = 100 mg/kg p.o.). Using the rat D-Ala2-Met5-enkephalinamide potentiation test the duration of action of SCH 34826 was at least 4 hs. No respiratory or gastrointestinal side effects of any consequence were noted at doses up to 100 times those active in the D-Ala2-Met-5-enkephalinamide potentiation test.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics,
http://linkedlifedata.com/resource/pubmed/chemical/Dioxolanes,
http://linkedlifedata.com/resource/pubmed/chemical/Dioxoles,
http://linkedlifedata.com/resource/pubmed/chemical/Dipeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Enkephalin, Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Naloxone,
http://linkedlifedata.com/resource/pubmed/chemical/Neprilysin,
http://linkedlifedata.com/resource/pubmed/chemical/enkephalinamide-Met, Ala(2)-
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-3565
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
245
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
829-38
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:3164388-Administration, Oral,
pubmed-meshheading:3164388-Analgesics,
pubmed-meshheading:3164388-Animals,
pubmed-meshheading:3164388-Dioxolanes,
pubmed-meshheading:3164388-Dioxoles,
pubmed-meshheading:3164388-Dipeptides,
pubmed-meshheading:3164388-Drug Synergism,
pubmed-meshheading:3164388-Enkephalin, Methionine,
pubmed-meshheading:3164388-Gastrointestinal Motility,
pubmed-meshheading:3164388-Male,
pubmed-meshheading:3164388-Metalloendopeptidases,
pubmed-meshheading:3164388-Mice,
pubmed-meshheading:3164388-Naloxone,
pubmed-meshheading:3164388-Neprilysin,
pubmed-meshheading:3164388-Rats,
pubmed-meshheading:3164388-Respiration
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pubmed:year |
1988
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pubmed:articleTitle |
Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic.
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pubmed:affiliation |
Research Division, Schering-Plough Corporation, Bloomfield, New Jersey.
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pubmed:publicationType |
Journal Article
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