Aminorex (2-amino-5-phenyl-2-oxazoline) is a substituted oxazoline derivative of amphetamine (Figure 1). It was originally synthesized in the early 1960s and marketed in Europe as an anorexic agent.1 This amphetamine analog increases norepinephrine concentrations in the CNS. Its use in Europe from 1967 to 1972 as an appetite suppressant led to an epidemic of primary pulmonary hypertension before the drug was withdrawn from the market.2,3 Aminorex and methylaminorex, a methyl-substituted analog of aminorex, were identified as drugs of abuse prepared from readily available compounds and were classified as US Drug Enforcement Agency Schedule I drugs.4,5
A number of drugs with similar actions used in weight control also caused increased incidence of pulmonary hypertension and valvular heart disease with subsequent fatal effects.6–8 The mechanism for the increase in pulmonary pressure remains elusive. Results of 2 studies9,10 suggest that anorexic agents can inhibit potassium current, cause membrane depolarization, and stimulate pulmonary vasoconstriction. Other investigators speculate that aminorex and similar drugs such as serotonin (5-hydroxytryptamine) are transporters of substrates that become translocated into pulmonary cells where, depending on the degree of drug retention and individual susceptibility, hypertension could develop as a response to high concentrations of these drugs or metabolites in circulation. Aminorex has pharmacologic actions similar to those of amphetamines in inducing CNS stimulation resulting in psychomotor and locomotor stimulation in mice and rats.11,12 Results of those studies suggest that aminorex is a CNS stimulant that may have substantial potential for amphetaminelike abuse in humans.
Aminorex was detected, quantified, and confirmed in plasma and urine samples collected after racing from horses. Aminorex and related substances are prohibited in the horse-racing industry. After the initial report of aminorex use in racehorses, horses continued to yield positive results for the drug. To the authors' knowledge, the clandestine sources of aminorex remain unknown. The purpose of the study reported here was to investigate the pharmacokinetic and pharmacologic effects of IV or PO administration of aminorex in horses and relate these concentrations to the plasma and urinary concentration detected after races in an attempt to differentiate the concentrations inducing a pharmacologic effect from those that are pharmacologically and clinically irrelevant.
High-performance liquid chromatography
Volume of central compartment
Area under the plasma concentration curve
Volume of compartment 2
Volume of compartment 3
Volume of distribution steady state
Total body clearance
Aminorex was prepared from 2-amino-1-phenylethanol according to standard procedures by C. Randall Clark, Harrison School of Pharmacy, Auburn University, Auburn, Ala.
Angiocath, Becton Dickinson, Sandy, Utah.
Chlorhexidine gluconate 4%, Purdue Fredrick Co, Stamford, Conn.
Chlorhexidine diacetate, Fort Dodge Health, Fort Dodge, Iowa.
Foley catheters, CR Bard Inc, Covington, Ga.
Bard center entry urinary drainage bag, CR Bard Inc, Covington, Ga.
Hewlett-Packard Telemetry, Atlanta, Ga.
Cerilliant, Round Rock, Tex.
Fisher Scientific, Fair Lawn, NJ.
LXQ/LC and auto-sampler, ThermoFisher Scientific, San Jose, Calif.
Mac-Mod Analytical, Chad Fords, Pa.
Excalibur software, version 2.0, Quan Browser, ThermoFisher Scientific, San Jose, Calif.
Simulation, analysis and modeling software, Available at: winsaam.com. University of Pennsylvanian, Kennet Square, Pa. Accessed May 8, 2007.
JMP, version 6.0, SAS Institute Inc, Cary, NC.
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