Levamisole, Aminorex, and Pulmonary Arterial Hypertension: A Review

Authors

1 Consultant Pathologist/Toxicologist, Berkeley, California, USA

2 Department of Health Sciences, Forensic Toxicology Division, University of Florence, Florence, Italy

Abstract

Context: An epidemic of aminorex-associated pulmonary arterial hypertension (PAH), resulting in multiple fatalities, occurred in the 1970s ending only after the drug was removed from the market. In 2009, when it was found that horses de-wormed with the anthelmintic levamisole, metabolized that drug to aminorex, the same drug that caused the 1970s outbreak of PAH. The discovery would not have been cause for concern except to horseracing enthusiasts, who feared horse doping. However, at about the same time the relationship between levamisole and aminorex was discovered, cocaine cartels began adulterating cocaine with levamisole. The rationale for adulterating cocaine with levamisole remains to be established. The purpose of this short review article is to discuss possible reasons for levamisole contamination, new discoveries about the human pharmacokinetics of aminorex, and the possible relationship between aminorex and pulmonary arterial hypertension in man. Evidence acquisition: Medline contents, as well as estimates published by the U.S. drug enforcement agency (DEA), US state department, and the European monitoring center for drugs and drug abuse (EMCDDA) were reviewed and relevant articles retrieved. There is uniform agreement among the various monitoring agencies analyzed. Results: Approximately 70 percent of the U.S. cocaine supply and 40 percent of the European cocaine supply is contaminated with levamisole. Aminorex has the same binding affinities for serotonin and other neurotransmitters as amphetamine. As serotonin is considered to be an important factor in the development of PAH, the possibility of another epidemic of aminorex-induced PAH, this time among cocaine abusers, seems real, and threatening. Conclusions: The results of the first human pharmacokinetic studies of aminorex were first characterized in 2013. The results suggest that while humans could produce aminorex from levamisole, they probably do not convert very much. Even though cases of PAH have been reported in cocaine users, the latest pharmacokinetic studies suggest that very little aminorex is actually produced from the ingested levamisole, probably not enough to cause PAH. However, since both cocaine and aminorex can cause PAH the situation remains unclear. the lack of a clear answer is partially the development of an insidious pulmonary hypertension, producing subtle and non-specific symptoms in its early stages.

Keywords

References

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Razavi International Journal of Medicine
Volume 3, Issue 3
July 2015
Pages 1-5

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