Spinal antinociception: Comparison of a dermorphin tetrapeptide analogue, [ d-arginine 2, sarcosine 4]-dermorphin (1–4) and morphine in rats

Abstract

Intracerebroventricular injections of [ d-arginine 2, sarcosine 4]-dermorphin (1–4)(DAS-DER 1–4) and morphine produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED 50 value for each drug was 3.23 (1.35–7.73) nmol/rat and 32.0 (13.3–76.6) nmol/rat, respectively. When injected into the spinal subarachnoid space, the ED 50 value was 0.035 (0.015–0.086) nmol/rat for the tetrapeptide and 11.9 (5.7–25.2) nmol/rat for morphine, respectively. Antinociception induced by DAS-DER 1–4 and morphine, through the intracerebroventricular and intrathecal routes, was clearly reduced by pretreatment with a small dose of naloxone. After spinal transection, the antinociceptive potency of systemically-administered morphine was significantly reduced while that of DAS-DER 1–4 was unaltered. The activity of DAS-DER 1–4 and morphine was also reversed by naloxone in spinal animals. It is concluded that DAS-DER 1–4, a dermorphin analogue, has a minor supraspinal action but acts mainly at the level of the spinal cord, in contrast to the action of morphine.