Uptake, metabolism and efflux of l-alpha-acetylmethadol (LAAM) by rat lung tissue

DH Lau and GL Henderson

The uptake, metabolism and efflux of the longacting narcotic analgesic l-alpha-[2-3H]acetylmethadol ([3H]LAAM) were studied using rat lung tissue slices. Uptake of [3H]LAAM by lung slices incubated in 1 micrometer [3H]LAAM in Krebs-Ringer phosphate buffer was rapid for the first 10 minutes, slow thereafter and reached equilibrium after 30 minutes. Less than 10% of the accumulated radioactivity was found to be in the form of the metabolites noracetylmethadol and methadol. LAAM accumulates in lung tissue primarily by passive diffusion and nonspecific binding. Uptake was against a concentration gradient and could be reduced significantly by iodoacetate or by boiling the tissue and slightly reduced by removing oxygen or Na+ from the medium. However, the uptake process was nonsaturable, was not affected by the removal of Ca++ or glucose from from the medium, lacked stereospecificity and was reversible. Efflux of accumulated [3H]LAAM from lung tissue was a first-order process with an apparent t1/2 of 46 minutes. Many drugs which may possibly be used by patients receiving LAAM, such as methadone, fentanyl, propoxyphene, norpropoxyphene, imipramine, promazine and chlorpromazine, were found to have a significant inhibitory effect on [3H]LAAM uptake and could displace accumulated [3H]LAAM from lung tissue.

Volume 206, Issue 1, pp. 143-150, 07/01/1978
Copyright © 1978 by American Society for Pharmacology and Experimental Therapeutics