L-tyrosine potentiation of opioid-induced analgesia utilizing the hot-plate test.
The effects of L-tyrosine (L-TYR) on the analgesic activity of several opioids were determined utilizing a hot-plate test. L-TYR (200 mg/kg) significantly potentiated (P < .05) the analgesic activity of morphine sulfate (10 mg/kg) and codeine sulfate (30 mg/kg). The opioid-induced analgesia and its potentiation by L-TYR was abolished by naloxone pretreatment. Increasing the dose of L-TYR (25-200 mg/kg) resulted in a dose-dependent potentiation of morphine-induced analgesia. The observed potentiation was positively correlated with increases in brain TYR concentrations; blockade of L-TYR uptake into the brain by the coadministration of L-valine attenuated this potentiation. With the exception of L-tryptophan, all other L-amino acids, as well as D-TYR, failed to mimic the potentiating action of L-TYR. As determined by alpha-methyl-p-TYR pretreatment, the L-TYR-induced potentiation was dependent upon increased catecholamine synthesis. These results demonstrate that L-TYR dose dependently potentiates the analgesic activity of opioids and are consistent with the requirement of the central conversion of L-TYR to catecholamines via TYR hydroxylase for this response.
Department of Pharmacology, Massachusetts College of Pharmacy, Boston.
K M
KM
Hull
D E
DE
Tolland
T J
TJ
Maher
D000698:Analgesia; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D003061:Codeine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism / Q000494:pharmacology*; D014633:Valine / Q000494:pharmacology; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D009270:Naloxone; D014443:Tyrosine; D019805:alpha-Methyltyrosine; D009020:Morphine; D014633:Valine; D003061:Codeine