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Recreational Use of Aminorex and Pulmonary Hypertension* FREE TO VIEW

Seán P. Gaine, MD, FCCP; Lewis J. Rubin, MD, FCCP; James J. Kmetzo, MD; Harold I. Palevsky, MD, FCCP; Thomas A. Traill, MD
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*From the Division of Pulmonary and Critical Care Medicine (Dr. Gaine), Division of Cardiology (Dr. Traill), Johns Hopkins University, Baltimore, MD; the Division of Pulmonary and Critical Care Medicine (Dr. Rubin), University of California at San Diego, San Diego, CA; the Division of Cardiology (Dr. Kmetzo), Doylestown Hospital, Doylestown, PA; and the Division of Pulmonary and Critical Care Medicine (Dr. Palevsky), University of Pennsylvania, Philadelphia, PA.

Correspondence to: Lewis J. Rubin MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of California at San Diego, San Diego, CA



Chest. 2000;118(5):1496-1497. doi:10.1378/chest.118.5.1496
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Pulmonary hypertension has been associated with ingestion of the appetite suppressant aminorex. A similar compound, 4-methyl-aminorex (street names, “U-4-E-uh” [pronounced euphoria] or “ice”), is a “designer” drug with central stimulant activity. This drug was discovered on the property of three individuals with diagnoses of pulmonary hypertension. The association between “recreational” aminorex manufacture and ingestion and the development of pulmonary hypertension is described.

Figures in this Article

Pulmonary hypertension has been associated with the ingestion of a variety of substances, including anorexic agents, cocaine, contaminated rapeseed cooking oil, and L-tryptophan.1The epidemic of primary pulmonary hypertension in Austria, Switzerland, and West Germany in the 1970s was attributed to the widespread use of the anorexic agent aminorex and subsided on removal of this drug from the market.2 Aminorex was never available legally in the United States. We describe a cluster of patients with pulmonary hypertension that we believe was the result of “recreational” aminorex ingestion.

Patient 1 is a 39-year-old man who owns a farm in rural Pennsylvania. He presented in February 1993 with an 8-month history of exertional dyspnea and syncope, and he was found to have a pulmonary artery pressure of 56/20 mm Hg (mean, 34 mm Hg) at cardiac catheterization. The pulmonary capillary wedge pressure was normal, but left ventricular ejection fraction was reduced to 40%. Patient 2, the 32-year-old wife of patient 1, developed exertional dyspnea and syncope in November 1993. Cardiac catheterization in August 1994 disclosed a pulmonary artery pressure of 60/38 mm Hg (mean, 48 mm Hg). Patient 3, the nephew of patient 1, age 28 years, presented in January 1993 with dyspnea and light-headedness; at cardiac catheterization in July 1993, he had a pulmonary artery pressure of 75/30 mm Hg (mean, 50 mm Hg). No underlying cause for pulmonary hypertension was found in any case, and all patients initially denied ingestion of potentially toxic substances. Left ventricular function was mildly and globally depressed in patients 1 and 2, although left-heart filling pressures were normal. Pulmonary hypertension has been persistent in all three patients, although echocardiography in patient 1 suggested that pressures may have improved. An investigation by federal Drug Enforcement Administration agents resulted in indictment of patient 1 following the discovery of a chemistry laboratory and > 20 lb of 4-methyl-aminorex, an amphetamine analog, in a barn that was sublet on the farm. Patient 3, who was not indicted, subsequently confirmed prior 4-methyl-aminorex ingestion.

We present three members of a family with diagnoses of pulmonary hypertension, who were subsequently discovered to have been involved with the illicit manufacture and use of a designer drug, 4-methyl-aminorex. Officials for the Drug Enforcement Administration confirmed that the cis-isomer of 4-methyl-aminorex (street names,“ U-4-E-uh” [pronounced euphoria] or “ice”) has appeared on the clandestine market as a “designer” drug alternative to methamphetamine (street name, “crank”). 4-Methyl-aminorex (Fig 1 ), which has gained attention due to its potential as a central stimulant of abuse and because of the ease with which it is synthesized, was recently classified as a schedule I substance.3 The drug is generally synthesized from the over-the-counter diet pill phenylpropanolamine HCl and is smoked as the free base or the HCl salt. Anecdotally, the drug is said to have a minor “speed-like” component, with a time of action of 4 to 6 h.

While an autosomal dominant family history is obtained in 10 to 15% of individuals with primary pulmonary hypertension, the majority of cases of are postulated to occur sporadically following a stimulus (ie, anorexogens) that, in susceptible individuals, results in pulmonary vascular injury.4 The occurrence of a“ cluster” of pulmonary hypertension cases around the apparent illicit use of an aminorex analog has not previously been described. This case presents a most unusual occurrence of “familial” pulmonary hypertension.

Figure Jump LinkFigure 1. Similar chemical structure of aminorex (left) and 4-methyl-aminorex (right).Grahic Jump Location
Rubin, LJ, Barst, RJ, Kaiser, LR, et al (1993) ACCP consensus statement: primary pulmonary hypertension.Chest104,236-250. [CrossRef] [PubMed]
 
Gurtner, HP Aminorex pulmonary hypertension. Fishman, AP eds.The pulmonary circulation: normal and abnormal1990,397-412 University of Pennsylvania Press. Philadelphia, PA:
 
Glennon, RA, Misenheimer, B Stimulus properties of a new designer drug: 4-methylaminorex (“U4Euh”).Pharmacol Biochem Behav1990;35,517-521. [CrossRef] [PubMed]
 
Gaine, SP, Rubin, LJ Primary pulmonary hypertension.Lancet1998;352,719-725. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Similar chemical structure of aminorex (left) and 4-methyl-aminorex (right).Grahic Jump Location

Tables

References

Rubin, LJ, Barst, RJ, Kaiser, LR, et al (1993) ACCP consensus statement: primary pulmonary hypertension.Chest104,236-250. [CrossRef] [PubMed]
 
Gurtner, HP Aminorex pulmonary hypertension. Fishman, AP eds.The pulmonary circulation: normal and abnormal1990,397-412 University of Pennsylvania Press. Philadelphia, PA:
 
Glennon, RA, Misenheimer, B Stimulus properties of a new designer drug: 4-methylaminorex (“U4Euh”).Pharmacol Biochem Behav1990;35,517-521. [CrossRef] [PubMed]
 
Gaine, SP, Rubin, LJ Primary pulmonary hypertension.Lancet1998;352,719-725. [CrossRef] [PubMed]
 
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