Antinociception and physical dependence produced by [D-Arg2] dermorphin tetrapeptide analogues and morphine in rats.

1. The antinociceptive effects of [D-Arg2] dermorphin tetrapeptide analogues, H-Tyr-D-Arg-Phe-Gly-NH2 and H-Tyr-D-Arg-Phe-beta-Ala-OH when administered subcutaneously (s.c.) in rats were measured by the tail-flick test. In addition, the appearance of typical withdrawal signs upon cessation of administration or on subsequent treatment with naloxone were measured after chronic administration of either peptide or morphine. 2. The dose of peptides and of morphine in the physical dependence test was determined from the AD50 to inhibit the tail-flick test in rats. Doses from 4 to 64 times the AD50 doses were employed in the s.c. administration schedules. 3. The intensity of the antinociception induced by either peptide was greater than that produced by morphine. Moreover, the antinociception induced by the peptides was of much longer duration than that produced by morphine. 4. Abrupt withdrawal after chronic administration of either peptide produced only slight loss of body weight. In contrast, morphine withdrawal produced sharp loss of body weight. 5. Naloxone precipitated withdrawal signs after chronic administration of either peptide were less intense than those after chronic morphine. 6. These results suggest that the antinociception produced by these peptides is more intense and of longer duration than that produced by morphine. It is also interesting to note that the physical dependence produced by these peptides is less marked than that produced by morphine.