Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate

  title={Pharmacokinetics and Pharmacodynamics of Methylecgonidine, a Crack Cocaine Pyrolyzate},
  author={Karl B. Scheidweiler and Mark A. Plessinger and Jalil Shojaie and Ronald W. Wood and Tai C. Kwong},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  pages={1179 - 1187}
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… 

Figures and Tables from this paper

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern

This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

Neurotoxicity of anhydroecgonine methyl ester, a crack cocaine pyrolysis product.

Investigation of the neurotoxicity of AEME and its possible cholinergic effects in rat primary hippocampal cell cultures that were exposed to different concentrations of AemE, cocaine, and a cocaine-AEME combination suggested a higher risk for neurotoxicity after smoking crack cocaine than after cocaine use alone.

Determination of cocaine, benzoylecgonine and methylecgonidine in urine specimens from individuals submitted to medical-legal investigations

The development and application of a method that is efficient and economically viable for the identification and quantification of crack biomarkers in urine samples from the Forensic Toxicology Laboratory of the Legal Medicine Institute of Sao Paulo is developed.

Cocaine, Crack Cocaine, and Ethanol

Analysis of Urinary Biomarkers for Smoking Crack Cocaine: Results of a Danish Laboratory Study.

It is advocated that the urinary biomarkers MED and ED are included in routine testing methods for clinical toxicology, which may lead to an earlier identification of crack cocaine smoking and possibly prevent a more severe drug use.

M1 and M3 muscarinic receptors may play a role in the neurotoxicity of anhydroecgonine methyl ester, a cocaine pyrolysis product

The selective M1 and M3 antagonists and the phospholipase C inhibitor, were able to prevent AEME-induced neurotoxicity, suggesting that the toxicity is due to the partial agonist effect at M1and M3 mAChRs, leading to DNA fragmentation and neuronal death by apoptosis.

Identification of anhydroecgonine ethyl ester in the urine of a drug overdose victim.

Toxicological evaluation of postmortem urine collected from a 41-year-old deceased white male detected anhydroecgonine ethyl ester (ethylecgonidine, AEEE), a transesterification product of smoked cocaine co-abused with ethanol, which is a potential additional forensic marker for the co-abuse of smoked Cocaine and ethanol.

Comparison of Cocaine/Crack Biomarkers Concentrations in Oral Fluid, Urine and Plasma Simultaneously Collected From Drug Users.

Despite the good correlations found in some cases, especially for BZE, the large variation in drug concentrations seen in this work suggests that OF concentrations should not be used to estimate concentrations of COC, BZE or AEC in plasma and/or urine.

Stability of methylecgonidine and ecgonidine in sheep plasma in vitro.

MEG is stable in sheep plasma collected in commercially available, evacuated blood-collection tubes containing NaF and stored at -80 degrees C, and its in vivo formation may provide a better marker of crack smoking than its parent pyrolysis product.

Negative inotropic effect of methylecgonidine, a major product of cocaine base pyrolysis, on ferret and human myocardium.

The physiological effects and potential mechanisms of action of methylecgonidine (MEG), the major pyrolysis product from smoking "crack cocaine," on cardiac function are examined and it is concluded that the NIE of MEG is caused by decreased calcium availability.

Comparison of heroin and cocaine concentrations in saliva with concentrations in blood and plasma.

The first reported observations of heroin and metabolites in saliva following heroin smoking and of AEME in saliva after smoking cocaine base are reported, which may be useful as a marker of the smoked route following cocaine administration.

Electron ionization mass fragmentometric detection of urinary ecgonidine, a hydrolytic product of methylecgonidine, as an indicator of smoking cocaine.

Ecgonidine was detected in > 95% of benzoylecgonine-positive urine specimens from a random drug testing program, indicating smoking as the major route of cocaine administration.

Identification of unique cocaine metabolites and smoking by-products in postmortem blood and urine specimens.

The identification of AEME in the specimens indicated that "crack" cocaine had been smoked, and the presence of CE indicated co-administration of cocaine and ethanol.

Simultaneous measurement of cocaine, cocaethylene, their metabolites, and "crack" pyrolysis products by gas chromatography-mass spectrometry.

We developed a sensitive and specific assay for the simultaneous measurement of cocaine, cocaethylene, six of their metabolites, and anhydroecgonine methyl ester, a pyrolysis product, in biological

Methylecgonidine coats the crack particle

Testing human hair and urine for anhydroecgonine methyl ester, a pyrolysis product of cocaine.

AEME was tested in 65 and 81 cases for hair and urine, respectively, where COC or BZE or both tested positive, clearly indicating that COC smoking is not frequent in France.

Evidence of crack use by anhydroecgonine methylester identification

The results suggest that AEME can be a useful marker for the detection of COC smoking in clinical and forensic cases.