THE EFFECT OF ALTERED THYROID FUNCTION ON THE ACTIONS AND FATE OF d,l-METHADONE

Rats treated with thiouracil or methimazole for 8 to 30 days showed tolerance to the actions of d,l-methadone as evidenced by the absence of general depression and body rigidity following a dose of 7.5 mgm./kgm. The increase in pain response threshold was also less. The latter effect was also observed for thyroid-ectomized rats. Rats fed thyroid powder were more susceptible to the toxic effects of methadone but the increase in pain response threshold did not differ significantly from control rats. Liver slices from thiouracil and thyroid fed rats metabolized methadone more slowly than those from controls. Tissue levels of methadone were higher in the thiouracil-treated and in the thyroid-fed rats than in the control animals. However, total urinary and fecal excretion of methadone in all groups showed no marked differences. An attempt was made to correlate these findings with cellular and enzyme changes which ensue with altered thyroid function.