Comparison of the antinociceptive effect between D-Arg containing dipeptides and tetrapeptides in mice

D-Arg containing dipeptides, H-Tyr-D-Arg-OMe and H-Tyr (Et)-D-Arg-OMe, and D-Arg2 substituted N-terminal tetrapeptides of dermorphin, H-Tyr-D-Arg-Phe-Gly-OEt and H-Tyr (Et)-D-Arg-Phe-Gly-OEt administered intracerebroventricularly exhibited dose-dependent antinociceptive activities in mice as measured by the tail pressure and phenylbenzoquinone writhing tests. The effects of these peptides used were significantly antagonized by the pretreatment with naloxone, indicating that these effects must be produced through opioid receptors. Furthermore, it is of conspicuous interest that the effects of tetrapeptides revealed in infinitestimal order (ED50 = 12.5 and 355.0 pmole in the tail pressure test and 3.1 and 53.0 pmole in the phenylbenzoquinone writhing test, respectively) and was much more potent and prolonged than those of morphine, not to mention dipeptides used. However, judging from the difference of peak times and the degree of the antagonism by naloxone, it was suggested that dipeptides and tetrapeptides used might act on different sites of action in the central nervous system.