Analgesic properties of a systemically-administered synthetic dipeptide of 5-hydroxytryptophan.
Synthetic peptides of 5-hydroxytryptophan (5-HTP), including N-acetyl-5-HTP-5-HTP amide (5-HTP-ACETYL-DP), specifically inhibit the binding of serotonin to serotonin binding protein. 5-HTP-ACETYL-DP also produces a long-lasting, opiate-sensitive analgesia following central, but not systemic administration. The present study evaluated an apolar derivative of 5-HTP dipeptide, N-hexanoyl-5-HTP-5-HTP amide (5-HTP-HEX-DP), for its analgesic properties in rats following systemic administration. 5-HTP-HEX-DP (5-50 mg/kg) significantly increased jump thresholds in a dose-dependent manner with peak analgesia occurring at 2.5 hr after injection, and lasting up to 5 hr. In the tail-flick assay, 5-HTP-HEX-DP (20 mg/kg) produced a significant antinociceptive effect at 1 hr post-injection using both high and low intensity levels of radiant heat. While 5-HTP-HEX-DP and morphine each elicited analgesia following acute administration, chronic (14 days) incremental dosing with 5-HTP-HEX-DP or morphine resulted in persistent analgesia in 5-HTP-HEX-DP-treated animals, and a loss of analgesia in morphine-treated rats. Thus, significant tolerance to morphine, but not 5-HTP-HEX-DP analgesia developed using this protocol. Hence, 5-HTP-HEX-DP is a systemically-active analgesic which fails to develop tolerance when administered daily over 14 days.
D006916:5-Hydroxytryptophan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004334:Drug Administration Schedule; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000700:Analgesics; C022197:N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophanamide; D006916:5-Hydroxytryptophan