UPTAKE, METABOLISM AND EFFLUX OF L-ALPHA-ACETYLMETHADOL (LAAM) BY RAT LUNG-TISSUE

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 143-150
Abstract
L-.alpha.-Acetylmethadol (LAAM), an orally active synthetic narcotic analgesic with a duration of action 3 times longer than methadone, is currently being evaluated as a substitute for methadone in the maintenance treatment of opiate addicts. The uptake, metabolism and efflux of the long-acting narcotic analgesic [3H]LAAM were studied using rat lung tissue slices. Uptake of [3H]LAAM by lung slices incubated in 1 .mu.M [3H]LAAM in Krebs-Ringer phosphate buffer was rapid for the first 10 min, slow thereafter and reached equilibrium after 30 min. Less than 10% of the accumulated radioactivity was in the form of the metabolites noracetylmethadol and methadol. LAAM accumulated 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 O2 or Na+ from the medium. The uptake process was nonsaturable, was not affected by the removal of Ca2+ or glucose from the medium, lacked stereospecificity and was reversible. Efflux of accumulated [3H]LAAM from lung tissue was a 1st-order process with an apparent t1/2 [half-life] of 46 min. Many drugs which may possibly be used by patients receiving LAAM, such as methadone, fentanyl, propoxyphene, norpropoxyphene, imipramine, promazine and chlorpromazine, had a significant inhibitory effect on [3H]LAAM uptake and could displace accumulated [3H]LAAM from lung tissue.

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