Abstract
The antinociceptive effect of the cyclic dipeptide cyclo[Tyr(Et)- homoarginine] (C.TEHA) was examined utilizing the tail flick test and the digitus pinching test in rats in comparison with the linear dipeptide Boc-Tyr(Et)-homoarginine-OMe (B.TEHM). Though both dipeptides administered into the lateral, 3rd and 4th cerebroventricles produced antinociceptive effects equipotent to morphine, except for the 4th cerebroventricular 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.p.) when administered into the 3rd cerebroventricle where its effect was demonstrated to be the most potent. However, naloxone had no significant effect on C.TEHA administered into the 3rd cerebroventricle in both tests. It was concluded that both dipeptides 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 a naloxone-resistant opioid system or a non-opioid system.
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