Metabolism of cathinone to (−)-norephedrine and (−)-norpseudoephedrine

“…Elle a également une activité sérotoninergique entraînant sa libération à partir de sites du striatum, comme l'amphétamine mais avec une puissance d'activité réduite au tiers [25].…”

Section: Pharmacologieunclassified

La toxicité du khat impose-t-elle une modification de la réglementation de son usage en Europe?

Bouvet

Hugbart

Baert

et al. 2012

Ann Toxicol Anal

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Résumé -Objectif : La consommation de khat (Catha edulis Forsk) est une pratique largement répandue dans les populations de l'est de l'Afrique. En Europe, elle concerne les migrants de première génération et leurs descendants. Le khat ne fait pas l'objet de contrôle au titre des conventions de l'ONU, lesquelles s'appuient sur une recommandation de l'OMS. Cependant, les États demeurent libres de réglementer le khat dans le cadre de leur législation nationale ; c'est le cas de la France et de certains pays européens. Cette discordance entre les réglementations interroge sur la dangerosité réelle ou supposée de cette plante. Méthodes : Nous avons utilisé le moteur de recherche bibliographique PubMed pour identifier les publications pertinentes relatives à sa toxicité. Résultats : L'usage chronique de khat est associé à des altérations de la régulation de la pression artérielle, et à une augmentation du risque d'infarctus du myocarde. Comme le cannabis, le khat peut être impliqué dans la survenue de troubles psychotiques. Le risque addictif n'est pas exclu. Chez l'animal, plusieurs études suggèrent que l'usage de khat favorise l'agressivité. Le caractère cancérogène n'est pas établi même si la génotoxicité est suspectée in vivo. Conclusion : Le risque de complications cardio-vasculaires et psychiatriques de l'usage régulier de khat, son caractère potentiellement cancérogène et la parenté chimique de la cathinone avec l'amphétamine sont autant d'arguments pour justifier l'inscription du khat sur la liste des stupéfiants réglementés. Mots clés : Khat, stupéfiant, réglementationAbstract -Objectives: Khat (Catha edulis Forsk) consumption is a widespread practice in populations of Eastern Africa. In Europe, it concerns the first-generation migrants and their descendants. Khat is not subject to control under UN conventions, which are based on a WHO recommendation. However, states remain free to regulate khat within the framework of their national legislation, such as in France and some European countries. This discordance among regulations questions the real or supposed dangerousness of this plant. Methods: We used the search engine of the bibliographic database PubMed, in order to identify the relevant publications on khat's toxicity. Results: Chronic use of khat is associated with deteriorations in the regulation of blood pressure, and an increased risk of myocardial infarction. Like cannabis, khat can be involved in the onset of psychotic disorders. The risk of addiction is not excluded. In animals, several studies suggest that khat use encourages aggressiveness. The carcinogenic nature has not been established, although genotoxicity is suspected in vivo. Conclusions: The risk of cardiovascular and psychiatric complications due to frequent use of khat, its potentially carcinogenic nature, and the chemical relationship of cathinone with amphetamine justify the inscription of khat in the list of controlled narcotics.

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“…Based on the performed study, authors matched the probable metabolism pathway (Fig. 1) based on the work demonstrated by Brenneisen et al [15]. With regard to the metabolic pathway published by Brenneisen et al, cathinone is metabolized to amino-alcohols by reduction of C-1 keto group, and two main metabolities are identified as norephedrine and norpseudoephedrine which are present in the (-) form with 1R configuration (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…With regard to the metabolic pathway published by Brenneisen et al, cathinone is metabolized to amino-alcohols by reduction of C-1 keto group, and two main metabolities are identified as norephedrine and norpseudoephedrine which are present in the (-) form with 1R configuration (Fig. 1 IV) [15].…”

Section: Introductionmentioning

confidence: 99%

A comprehensive computational analysis of cathinone and its metabolites using quantum mechanical approaches and docking studies

et al. 2016

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Conformers of the psychoactive compound of the Khat plant cathinone along with its amino alcohol metabolites norephedrine and norpseudoephedrine have been calculated using DFT (M062X/B3LYP) and MP2 levels of theory for gas and solution phases. Gas-phase studies revealed that cathinone has two, norephedrine has four and norpseudoephedrine has three low-energy conformations with all conformers connected by rotational transition states. To understand the solvent effect to the energetic profiles of the studied species, the conductor-like screening model is employed within aqueous medium. It explains lowering of energy of all studied conformers in solution. The molecular electrostatic potential surface data for each molecule revealed likely reaction sites for the studied molecules. The computed IR spectra for cathinone and its metabolites have been compared with experimental data and rotational transition states connecting all conformers have been reported. The natural bond orbital analyses for only ligands and separately for their complexes with amino acid residues in protein pockets from the docking results are also performed to corroborate the results obtained from the MP2 and DFT calculations. The comprehensive computational study explore important amino acid residues and stabilizing energy of the studied molecules with the interacting proteins along with the reason behind the difference in potency for cathinone's metabolites.

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Metabolism of cathinone to (−)-norephedrine and (−)-norpseudoephedrine

Cited by 97 publications

References 11 publications

Psychopharmacological aspects of catha edulis (khat) and consequences of long term use: a review

Psychopharmacological aspects of catha edulis (khat) and consequences of long term use: a review

La toxicité du khat impose-t-elle une modification de la réglementation de son usage en Europe?

A comprehensive computational analysis of cathinone and its metabolites using quantum mechanical approaches and docking studies

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