The Distribution of Morphine in the Brain in Fatal Cases Due to the Intravenous Administration of Heroin

Abstract

Heroin (3,6-diacetylmorphine) is deacetylated in the human body to 6-mono-acetylmorphine and finally to morphine. These metabolites are responsible for the major pharmacologic effects of heroin (I,2). Since the conversion of heroin to morphine is rapid, it is that metabolite that has been measured in tissues following administration. In deaths due to heroin overdose, the tissue distribution of morphine has been studied (3),but the concentrations in brain regions have scldom been reported. The most extensive study of brain morphine concentrations following the intravenous administration of heroin was that of Richards et al. (4), who provided blood:brain correlations in 50 cases. This study did not, however, utilize any particular section of the brain. Animal studies have indicated a close relationship between the concentration of morphine in the brain and the degree of analgesia (5,6). In these studies, entire rat brains were homogenized and aliquots analyzed, thus yielding no information on distribution within the brain. The investigation of the fine distribution of morphine has been hindered by the lack of sensitivity of analytical procedures for morphine. In 1970 Spector and Parker (7) reported the production of antibodies to morphine using 3-0 carboxymethoxy-morphine-bovine serum albumin. Spector and Parker employed this morphine antibody in quantitative determination of morphine by a competitive binding assay using the ability of morphine to inhibit binding of dihydromorphine3H to the antimorphine antibody. The radioimmunoassay for morphine has a sensitivity of less than I ng morphine added and a specificity sufficient to detect and quantitate morphine in biological samples without extraction of the drug. The sensitivity and specificity of morphine radioimmunoassay has been applied to the study of morphine distribution in postmortem human tissues by Coubis and Kaul (8). Spiehler et al. have compared results for quantitative determination of morphine in urine, postmortem blood, bile, brain, and lung by radioimmunoassay, enzyme immunoassay, and spectrofluorometry (9). From our preliminary study (9). it appears that morphine radioimmunoassay possesses the necessary sensitivity for determination of morphine distribution in the brain.