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تسجيل

Amfetamines and other stimulants

المؤلف:  Sue Jickells , Adam Negrusz (Editors)

المصدر:  Clarkes Analytical Forensic Toxicology

الجزء والصفحة:  P25-26

2026-09-14

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Amfetamines and other stimulants

The amfetamines are metabolised by a combination of hydroxylation of the ring and the side chain carbon atom adjacent to the ring, and removal of the nitrogen (Fig. 1). Drugs with alkyl groups on the nitrogen are dealkylated (methamfetamine and methylene dioxymethylamfetamine (MDMA)) to other active amfetamines (amfetamine and methyl enedioxyamfetamine (MDA), respectively; Fig. 1). Methylenedioxyethylamfetamine (MDEA) and MDMA are both metabolised to MDA as well as other metabolites. The methyl enedioxyamfetamines are also transformed into dihydroxy compounds (catechols) following opening of the ring. These hydroxy metabolites can be either monomethylated or conjugated with sulfate esters or with glucuronic acid. The side chain of non-N-substituted amfetamines is oxidised to form benzoic acid derivatives (e.g. amfetamine), which are excreted as the glycine conjugate, or the sulfate or glucuronide conjugate. Amfetamine and methylamfetamine are also oxidised at the b-carbon to form the pharmacologically active ephedrine analogues. A number of legal stimulant drugs are metabolised to methylamfetamine or amfetamine. These include benzfetamine, clobenzorex, fenethylline, fenproporex and mefenorex. The antiparkinsonian drug selegiline is metabolised to the weakly active l-isomer of methylamfet amine. Detection of the parent drug and possibly the conduct of chiral analyses are essential to determine the source of the amfetamine. As expected from its different structure, cocaine undergoes substantially different routes of metabolism from the amfetamine class. Cocaine is hydrolysed rapidly by ubiquitous enzymes to the inactive benzoylecgonine. This is the main metabolite in both blood and urine. Other significant metabolites are ecgonine methyl ester (EME) and ecgonine (Fig. 2). Anhydroecgonine methyl ester (AEME, also known as methyl ecgonidine) is a pyrolytic substance formed by smoking cocaine. Coca ethylene is also found as a metabolite in persons who co-consume alcohol. Metabolism of cocaine to norcocaine allows the oxidation of the nitrogen to N-hydroxy norcocaine. N-Nitroso norcocaine and the N-oxide are also produced in small amounts.

Figure 1 Major routes of amfetamine metabolism.

Figure 2 Main cocaine metabolic pathways.