L-tyrosine potentiation of opioid-induced analgesia utilizing the hot- plate test

KM Hull, DE Tolland and TJ Maher

Department of Pharmacology, Massachusetts College of Pharmacy, Boston.

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.

Volume 269, Issue 3, pp. 1190-1195, 06/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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