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Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate.
J Pharmacol Exp Ther. 2003 Dec; 307(3):1179-87.JP

Abstract

Methylecgonidine is formed from cocaine base when smoked and has been identified in biological fluids of crack smokers. Ecgonidine, a metabolite of methylecgonidine formed via esterase activity, also has been identified in similar samples collected from crack smokers. Methylecgonidine and ecgonidine can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of methylecgonidine and ecgonidine in sheep after intravenous administration of methylecgonidine at doses of 3.0, 5.6, and 10.0 mg/kg using gas chromatography-mass spectrometric assays. Methylecgonidine clears quickly from blood with a half-life of 18 to 21 min, whereas ecgonidine has a longer half-life of 94 to 137 min. Because ecgonidine 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 methylecgonidine, decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that methylecgonidine produces cardiovascular effects in vivo consistent with muscarinic agonism, methylecgonidine 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. Two of the three sheep demonstrated mild bradycardia 3 to 5 min after methylecgonidine injection. Intravenous pretreatment with atropine methyl bromide (15 microg/kg) antagonized methylecgonidine-induced hypotension in all three sheep, supporting the hypothesis that methylecgonidine acts as a muscarinic agonist in vivo.

Authors+Show Affiliations

University of Rochester School of Medicine, Rochester, NY, USA. kscheidweiler@intra.nida.nih.govNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14561847

Citation

Scheidweiler, Karl B., et al. "Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate." The Journal of Pharmacology and Experimental Therapeutics, vol. 307, no. 3, 2003, pp. 1179-87.
Scheidweiler KB, Plessinger MA, Shojaie J, et al. Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate. J Pharmacol Exp Ther. 2003;307(3):1179-87.
Scheidweiler, K. B., Plessinger, M. A., Shojaie, J., Wood, R. W., & Kwong, T. C. (2003). Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate. The Journal of Pharmacology and Experimental Therapeutics, 307(3), 1179-87.
Scheidweiler KB, et al. Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate. J Pharmacol Exp Ther. 2003;307(3):1179-87. PubMed PMID: 14561847.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacokinetics and pharmacodynamics of methylecgonidine, a crack cocaine pyrolyzate. AU - Scheidweiler,Karl B, AU - Plessinger,Mark A, AU - Shojaie,Jalil, AU - Wood,Ronald W, AU - Kwong,Tai C, Y1 - 2003/10/15/ PY - 2003/10/17/pubmed PY - 2004/1/30/medline PY - 2003/10/17/entrez SP - 1179 EP - 87 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 307 IS - 3 N2 - Methylecgonidine is formed from cocaine base when smoked and has been identified in biological fluids of crack smokers. Ecgonidine, a metabolite of methylecgonidine formed via esterase activity, also has been identified in similar samples collected from crack smokers. Methylecgonidine and ecgonidine can be used as biomarkers to differentiate smoking from cocaine use via other routes of administration. We determined the pharmacokinetic properties of methylecgonidine and ecgonidine in sheep after intravenous administration of methylecgonidine at doses of 3.0, 5.6, and 10.0 mg/kg using gas chromatography-mass spectrometric assays. Methylecgonidine clears quickly from blood with a half-life of 18 to 21 min, whereas ecgonidine has a longer half-life of 94 to 137 min. Because ecgonidine 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 methylecgonidine, decreasing contractility and stimulating nitric oxide production in cardiac cells and tissues. To test the hypothesis that methylecgonidine produces cardiovascular effects in vivo consistent with muscarinic agonism, methylecgonidine 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. Two of the three sheep demonstrated mild bradycardia 3 to 5 min after methylecgonidine injection. Intravenous pretreatment with atropine methyl bromide (15 microg/kg) antagonized methylecgonidine-induced hypotension in all three sheep, supporting the hypothesis that methylecgonidine acts as a muscarinic agonist in vivo. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/14561847/Pharmacokinetics_and_pharmacodynamics_of_methylecgonidine_a_crack_cocaine_pyrolyzate_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=14561847 DB - PRIME DP - Unbound Medicine ER -