Spinal antinociception: comparison of a dermorphin tetrapeptide analogue, [D-arginine2, sarcosine4]-dermorphin (1-4) and morphine in rats.
Intracerebroventricular injections of [D-arginine2, sarcosine4]-dermorphin (1-4) (DAS-DER 1-4) and morphine produced a dose-dependent inhibition of the tail-flick response to thermal stimulation. The ED50 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 ED50 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.
Nakata
N
N
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Sakurada
S
S
Sakurada
T
T
Kawamura
S
S
Kisara
K
K
Suzuki
K
K
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003655:Decerebrate State; D007267:Injections; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013346:Subarachnoid Space
D000700:Analgesics; D009842:Oligopeptides; C047133:dermorphin (1-4), Arg(2)-Sar(4)-; D009270:Naloxone; D009020:Morphine