Suppression of craving and withdrawal in humans addicted to narcotics or amphetamines by administration of alpha-methyl-para-tyrosine (AMPT) and 5-butylpicolinic acid (fusaric acid)

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Drug addiction is a worldwide problem and its solution depends on the efforts of many disciplines. Two aspects of the treatment of the individual addict relate to prevention of the craving and dependence, be they psychological or physical, and to the prevention of the withdrawal or abstinence syndrome. Attempts to accomplish these objectives in a pharmacological manner can be considered in two major categories: the replacement of the offending drug with one more acceptable, although still addictive, and the use of compounds that may alter the biochemical basis of addiction and withdrawal symptoms.

Previous experimental work by Pozuelo and Kerr1 in morphine addicted monkeys demonstrated that treatment with alpha-methyl-paratyrosine (AMPT) abolished the craving for morphine and diminished or abolished the manifestations of the abstinence syndrome. When the results of this investigation were presented at the First International Congress on Alcoholism and Addiction (June 5 to 10, 1972, Seville, Spain) it was suggested that AMPT could be used “. . . in the treatment of narcotic and amphetamine addictions and other mental conditions where the catecholamines were known to play a fundamental role.” Later, Davis and Smith2 demonstrated that AMPT prevented the self-administration of morphine and amphetamines in addicted rats.

The encouraging results of these experiments led, in 1972, to the trial of AMPT in four patients addicted to morphine. They all developed AMPT crystalluria, as in retrospect, had the monkeys, and treatment was discontinued.

It was my impression that alkalinization of the urine to pH 8 or above could prevent . . .



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