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1 School of Pharmacy, and the Departments of Pharmacology, School of Medicine, University of California, San Francisco, and University of Berne, Switzerland
2 Department of Pharmacology University of Utah, Salt Lake City, Utah
The metabolism of heroin was investigated in mice using a method which simultaneously measured heroin and two of its biotransformation products, 6-monacetylmorphine (MAM) and morphine in the total animal carcass and various organs. Heroin was found to be rapidly metabolized in vitro and in vivo. Deacetylation of heroin to MAM and morphine was found to occur most rapidly and to the greatest degree in the liver. Absorption of heroin after subcutaneous administration was found to be extremely rapid; over 80% of the injected dose was absorbed within 15 minutes. There was a rapid disappearance of heroin from the animal body after intravenous administration, the biologic half-life being approximately 2.5 minutes. The heroin disappearance was accompanied by a rapid appearance of MAM in the brain and after a brief interlude by the appearance also of morphine. Toxicity studies with heroin, MAM and morphine were carried out using three modes of administration. The relative toxicity of each compound with each route of administration was as follows: subcutaneous, heroin = MAM > morphine; intravenous, heroin > MAM > morphine; intracerebral, morphine > heroin > MAM. It was concluded that the phamacologic effects of heroin, excepting possibly for a brief interval during the initial phase of drug effect, are primarily mediated by MAM and morphine. Heroin penetrates the central nervous system
largely as MAM and to a much lesser degree as morphine. Morphine levels in the brain may also result from local deacetylation of MAM. During peak effects of heroin, it is probable that both MAM and morphine are eliciting pharmacologic actions but persistence of heroin effects are mainly attributable to morphine.
Submitted on November 12, 1959
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