Amfetamine and methamfetamine
Amfetamine and methamfetamine are indirect sympathomimetic agents giving rise to release of norepinephrine (noradrenaline) and inhibition of monoamine oxidase. Effects via this action result in hypertension, tachycardia, and inhibition of gut motility. It was this last effect that led to their medical use in treating obesity. However, they are also CNS stimulants and their effect on the CNS soon led to these drugs being abused.
Amfetamine (a-methylphenethylamine) and methamfetamine (N-methyl-a-methylphenethy lamine) (Fig. 1) in free-base form are both liquids. Amfetamine is normally produced as amfetamine sulfate, hydrochloride or phosphate and is more commonly abused in Europe than is methamfetamine. Methamfetamine is normally produced as methamfetamine hydrochloride and is more popular in North America and Japan than is amfetamine.
Street-level amfetamine and methamfetamine are normally submitted to the laboratory as white to off-white powders with relatively low purity (e.g.<20%) but may sometimes occur in tablet form (Fig. 1).
Figure 1 (A) Amfetamine and (B) methamfetamine and (C) examples of forms in which these drugs occur.
Synthesis of amfetamine and methamfetamine Many methods are available for the illicit synthesis of amfetamine, but the Leuckart reaction has been the most popular. This method is simple, rapid, gives a good yield and does not involve any particularly hazardous chemicals or procedures. It may be considered as a three-step reaction that involves the condensation of phenyl-2-propanone (P-2-P) with formamide followed by a hydrolysis of the N-formylam fetamine and finally purification by steam distillation (Fig. 2).
Methamfetamine can be made by the Leuckart reaction using either methylamine and formic acid or N-methyl formamide in the condensation step (Fig. 2). Common adulterants for amfetamine include caffeine to increase the stimulant effect and/or to mask low levels of the drug, and sugars (e.g. lactose) used as a diluent. Amfetamine and methamfetamine have isomeric (enantiomeric) forms. Studies have shown that the d-isomer has a more potent effect on the CNS system than the l-isomer and that the d-isomer is eliminated from the body slightly faster than the l-isomer.
Figure 2 Leuckart reaction for the synthesis of amfetamine and methamfetamine.
