Chloroephedrine: contaminant of methamphetamine synthesis with cardiovascular activity

• Published in: Drug and alcohol dependence 2001-11, Vol.64 (3), p.299-307
• Main Authors: Varner, Kurt J, Hein, Nichole D, Ogden, Brian A, Arsenault, Jody R, Carter, Karen M, Soine, William H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Cardiovascular System - drug effects; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - chemical synthesis; Central Nervous System Stimulants - pharmacology; chloroephedrine; Dose-Response Relationship, Drug; Drug addictions; Drug Combinations; Drug Contamination; Ephedrine; Ephedrine - administration & dosage; Ephedrine - analogs & derivatives; Ephedrine - chemical synthesis; Ephedrine - pharmacology; Heart rate; Heart Rate - drug effects; Illicit synthesis; Injections, Intravenous; Isomerism; Male; Medical sciences; Methamphetamine - administration & dosage; Methamphetamine - chemical synthesis; Methamphetamine - pharmacology; Pseudoephedrine; Rat; Rats; Rats, Sprague-Dawley; Toxicology
• ISSN: 0376-8716; 1879-0046
• DOI: 10.1016/S0376-8716(01)00132-6

Chloroephedrine is an intermediate and possible contaminant formed when methamphetamine is manufactured using ephedrine or pseudoephedrine as precursors. The purpose of this study was to determine whether this contaminant has biological activity and might contribute to methamphetamine-induced cardiovascular toxicity. In conscious rats, the (−) and (+) isomers of chloroephedrine (0.1 and 1.0 mg/kg, i.v.) dose-dependently increased mean arterial pressure (MAP) and heart rate (HR). The potency of the pressor effects of (−) and (+)-chloroephedrine was between that of ephedrine and pseudoephedrine. The increases in HR elicited by the four stimulants were similar except that the tachycardia elicited by all doses of ephedrine and pseudoephedrine were preceded by a brief decrease in HR. The i.v. administration of 10 mg/kg of (+) or (−)-chloroephedrine produced biphasic (decrease followed by increase) the MAP and HR responses. Ephedrine and pseudoephedrine did not decrease MAP at any dose tested. The initial decrease in HR elicited by (−)-chloroephedrine was significantly reduced and the hypotensive response abolished by atropine, indicating that these components of the MAP and HR responses resulted from vagal activation. The secondary pressor response elicited by (−)-chloroephedrine was significantly reduced and the tachycardia significantly increased by pretreatment with phentolamine (3 mg/kg, i.v.). The increase in HR was reversed by propranolol. These results indicate that (−) and (+)-chloroephedrine have sympathomimetic properties similar to other known sympathomimetic stimulants. In addition, larger doses of chloroephedrine can activate the vagus nerve. The combination of (+)-methamphetamine and (−)-chloroephedrine did not markedly alter the magnitude of the MAP and HR responses of (+)-methamphetamine alone except at high doses of (−)-chloroephedrine (10 mg/kg). Contamination of illicit methamphetamine with chloroephedrine may have toxic consequences.