Enhancement of a kappa-opioid receptor agonist-induced analgesia by L-tyrosine and L-tryptophan.
The effects of the methyl esters of L-tyrosine (L-Tyr-OMe) and L-tryptophan (L-Trp-OMe) on the analgesic action of trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidin)cyclohexyl]-benzene acetamide methane sulfonate (U-50,488H), a kappa-opioid receptor agonist, were determined in male Swiss-Webster mice using the tail-flick test. Intraperitoneal injections of U-50,488H produced a dose-dependent analgesic response. The analgesic response to all doses of U-50,488H was potentiated by L-Tyr-OMe at 200 mg/kg injected intraperitoneally 30 min prior to the injection of U-50,488H. The effect of various doses of L-Tyr-OMe (50, 100 and 200 mg/kg) on the analgesia produced by 20 mg/kg of U-50,488H was also determined. The lowest dose (50 mg/kg) of L-Tyr-OMe did not modify U-50,488H-induced analgesia but the two higher doses enhanced it significantly. L-Tyr-OMe by itself at all the doses tested had no effect on the tail-flick latency. L-Trp-OMe (200 mg/kg) enhanced the analgesic action of 10 and 20 mg/kg doses of U-50,488H but not that induced by a 5 mg/kg dose. The analgesia induced by 20 mg/kg of U-50,488H was potentiated by L-Trp-OMe at 100 and 200 mg/kg but not by a 50 mg/kg dose. L-Trp-OMe by itself also did not alter the tail-flick latency. Previously, the studies in this laboratory have shown that L-Try-OMe potentiates morphine, a mu-opioid receptor agonist-induced analgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
Barjavel
M J
MJ
Department of Pharmaceutics and Pharmacodynamics (M/C 865), University of Illinois at Chicago 60612.
Thorat
S N
SN
Bhargava
H N
HN
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D010147:Pain Measurement; D011759:Pyrrolidines / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000187:drug effects* / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000700:Analgesics; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C040444:tyrosine methyl ester; D014443:Tyrosine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C028129:tryptophan methyl ester; D014364:Tryptophan