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.[1]References
- Antinociceptive effect of some carboxypeptidase A inhibitors in comparison with D-phenylalanine. Giusti, P., Carrara, M., Cima, L., Borin, G. Eur. J. Pharmacol. (1985) [Pubmed]
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