Pharmacokinetics and Pharmacodynamics of Methylecgonidine,
a Crack Cocaine Pyrolyzate
Scheidweiler KB, Plessinger MA,
Shojaie J, Wood RW, Kwong TC.
Department of Pathology and Laboratory Medicine.
J Pharmacol Exp Ther. 2003 Oct 15
ABSTRACTMethylecgonidine (MEG) is formed from cocaine base when smoked and has been identified in biologic fluids of crack smokers. Ecgonidine (EC), a metabolite of MEG formed via esterase activity, also has been identified in similar samples collected from crack smokers. MEG and EC can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of MEG and EC in sheep following intravenous administration of MEG at doses of 3.0, 5.6 and 10.0 mg/kg employing gas chromatography- mass spectrometric assays. MEG clears quickly from blood with a half-life of 18-21 minutes, while EC has a longer t1/2 of 94-137 minutes. Since EC clears more slowly it may be a more effective biomarker of cocaine smoking. The cardiovascular stimulant effects of cocaine contrast with reported in vitro muscarinic agonist effects of MEG decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that MEG produces cardiovascular effects in vivo consistent with muscarinic agonism, MEG was administered to sheep intravenously (0.1-3.0 mg/kg) while monitoring heart rate and blood pressure. Significant hypotension and tachycardia occurred in all three sheep (p<0.005). Two of the three sheep demonstrated mild bradycardia 3-5 minutes after MEG injection (p<0.005). Intravenous pretreatment with atropine methyl bromide (15 micro g/kg) antagonized MEG-induced hypotension in all three sheep, supporting the hypothesis that MEG acts as a muscarinic agonist in vivo.History
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