Tolerance and cross-tolerance to the antinociceptive effects of [D-Arg2]-dermorphin tetrapeptide analogue and morphine.
Rats were given repeated subcutaneous injections of [D-Arg2, Sar4]-dermorphin (1-4) [DAS-DER-(1-4)] and/or morphine over a period of 4 or 7 days. Antinociception was determined at 90 min for DAS-DER (1-4) and 30 min for morphine after each morning injection (9:00 a.m.), using the tail-flick and digit pinching tests in rats. Subcutaneous administration of DAS-DER (1-4) and morphine produced the development of antinociceptive tolerance, respectively. A marked tolerance to DAS-DER (1-4) and morphine was seen in rats made tolerant to morphine. However, administration of morphine produced no significant decrement in the antinociceptive activity in rats made tolerant to DAS-DER (1-4). These results suggest that the site of action of DAS-DER (1-4) may be more limited than that of morphine in the nociceptive pathways, for lack of its antinociceptive efficacy in morphine-tolerant rats.
Sakurada
S
S
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Nakata
N
N
Sakurada
T
T
Chaki
K
K
Kawamura
S
S
Kisara
K
K
Suzuki
K
K
D000595:Amino Acid Sequence; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance; D008297:Male; D008969:Molecular Sequence Data; D009020:Morphine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000700:Analgesics; D009842:Oligopeptides; C047133:dermorphin (1-4), Arg(2)-Sar(4)-; D009020:Morphine; C045484:dermorphin, Arg(2)-