Pharmacokinetics and Pharmacodynamics of Methylecgonidine,
a Crack Cocaine Pyrolyzate
by
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
Oral cocaine
Passive inhalation
Dopaminergic flies?
Dopaminergic agents
The coke-craving brain
Cocaine and depression
Cocaine and the lonely rat
Crack smoking and Brillo pads
Cocaine smoking and crack hands
01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24
Refs
HOME
HedWeb
cannabis-marijuana.com
Future Opioids
BLTC Research
Wirehead Hedonism
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best to Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family
