Abstract
Some 2-substituted-(2'-aminophenyl)-4-thioxohydantoic acids (o-amino PTC-amino acids) have antinociceptive activity when administered (icv) alone (IC50 = 0.04-0.87 microM/animal) and show a striking prolongation of the antinociceptive action of (D-Ala-2 D-Leu5)-enkephalin (DADL) in combination. The effects are thought to be mediated via opioid receptors since they are naloxone-reversible. Although inhibitors of the enkephalin degrading puromycin-insensitive, bestatin-sensitive aminopeptidase (possibly aminopeptidase M) their action is weak (IC50 = 32 microM leucine, 536 microM, glycine) and they might be considered to have a direct antinociceptive effect on opioid receptors. The titled compounds constitute novel 'lead' compounds for the development of potent aminopeptidase M inhibitors.
MeSH terms
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Aminopeptidases / antagonists & inhibitors
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Analgesics*
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Animals
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Glycine / analogs & derivatives*
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Glycine / chemical synthesis
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Glycine / pharmacology
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Indicators and Reagents
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Leucine / analogs & derivatives*
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Leucine / chemical synthesis
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Leucine / pharmacology
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Mice
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Naloxone / pharmacology
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Neprilysin / antagonists & inhibitors*
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Pain / physiopathology*
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Proline / analogs & derivatives*
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Proline / chemical synthesis
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Proline / pharmacology
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Protease Inhibitors / chemical synthesis*
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Thiohydantoins / chemical synthesis*
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Thiohydantoins / pharmacology
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Thiorphan / pharmacology
Substances
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Analgesics
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Indicators and Reagents
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Protease Inhibitors
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Thiohydantoins
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N(5)-(2'-aminophenyl)-4-thioxohydantoic acid
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2-(2'-methylpropyl)-N(5)-(2'-aminophenyl)-4-thiohydantoic acid
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N-(N'-(2'-nitrophenyl)thiocarbamyl)pyrrolidine-2-carboxylic acid
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Naloxone
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Proline
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Thiorphan
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Aminopeptidases
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Neprilysin
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Leucine
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Glycine