Abstract
The antinociceptive effect of cyclic dipeptide, cyclo[Tyr(Et)-homoarginine](C.TEHA) was examined using tail flick test and digitus pinching test in rats in comparison with linear dipeptide, Boc-Tyr(Et)-homoarginine-OMe(B.TEHM). Though both dipep-tides administered into the lateral, the 3rd and the 4th cere-broventricle produced antinociceptive effect eguipotent to morphine,except the 4th cerebroventricle administration of B.TEHM, the administration into the spinal subarachnoid space was without effect. The effect of B.TEHM was completely antagonized by the pretreatment of naloxone(i.ρ.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the strongest, but naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipep-tides act on the upper brain stem, especially around the 3rd cerebroventricle. Moreover, it was also thought that the effect of B.TEHM may be involved in the brain opioid system,and that of C.TEHA can be produced via naloxone-resistant opioid system or non-opioid system.
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