Analgesic properties of N-terminal substituted phenylalanyl-alanine.
Phenylalanylalanine, an in vitro inhibitor of enkephalinase, and some of its N alpha-derivatives are shown to possess an analgesic action when injected i.p. and i.c.v. into mice in the presence or absence of Leu5-enkephalin. In the second case a synergistic response is observed. The intensity of the analgesic response depends markedly on the nature of the N-terminal substituent which affects the hydrophobic character of the resulting dipeptide, its subsequent transport and probably its rate of biotransformation by cleaving enzymes.
D000215:Acylation; D000700:Analgesics; D000818:Animals; D004151:Dipeptides / Q000494:pharmacology; D004357:Drug Synergism; D004743:Enkephalin, Leucine / Q000494:pharmacology; D005260:Female; D007700:Kinetics; D051379:Mice; D015260:Neprilysin; D011480:Protease Inhibitors; D013329:Structure-Activity Relationship
D000700:Analgesics; D004151:Dipeptides; D011480:Protease Inhibitors; C039553:N-benzyloxycarbonylphenylalanylalanine; C039555:N-trifluoroacetylphenylalanylalanine; C039552:phenylalanylalanine; C039554:t-butyloxycarbonylphenylalanylalanine; D004743:Enkephalin, Leucine; D015260:Neprilysin