Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine.
It had previously been shown that D-phenylalanine and hydrocinnamic acid, two in vitro inhibitors of carboxypeptidase A, possess an analgesic action when injected i.p. in mice. We have studied the in vivo effects of indole-3-acetic acid, another carboxypeptidase A inhibitor, and of the following analogs of D-phenylalanine substituted in position 4: D-tyrosine, p-fluoro-D-phenylalanine and trifluoroacetyl-p-fluoro-D-phenylalanine. Whereas indole-3-acetic acid caused a higher and shorter analgesia in comparison with D-phenylalanine, p-fluoro-D-phenylalanine and its N-trifluoroacetyl derivative yielded both a greater and a much longer lasting analgesic effect. Since the latter compound showed only slight inhibitory activity on carboxypeptidase A in vitro, we suggest that inhibition of this enzyme and analgesia might not be directly correlated.
D000700:Analgesics; D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors*; D043422:Carboxypeptidases A; D005260:Female; D006993:Hypnotics and Sedatives; D007210:Indoleacetic Acids / Q000494:pharmacology; D051379:Mice; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology*; D010666:Phenylpropionates / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000494:pharmacology
D000700:Analgesics; D006993:Hypnotics and Sedatives; D007210:Indoleacetic Acids; D010666:Phenylpropionates; D014443:Tyrosine; C027218:3-fluorophenylalanine; D010649:Phenylalanine; C035253:3-phenylpropionic acid; C030737:indoleacetic acid; D002268:Carboxypeptidases; D043422:Carboxypeptidases A