The University of Arizona
 

History, Pharmacology, and Prevalence
Methamphetamine Overview:
Chemistry

Amphetamines are man-made chemicals that bear a close resemblance to several naturally occurring substances―phenylethylamine, for example, which is found in various food stuffs, including chocolate, cheeses, and some wines.  When consumed, phenylethylamine has little or no effect because it is rapidly degraded by the enzyme monoamine oxidase.[1]

Amphetamine is a simple synthetic derivative of phenylethylamine, which differs only in possessing a methyl group (-CH3) attached to the side chain (see chemical structures of phenylethylamine and amphetamine presented on the right).  This is a significant alteration, however, as the methyl group protects amphetamine from degradation by monoamine oxidase.  As a result, amphetamine can enter and persist in the bloodstream, positioning it to exert a variety of biological effects.[1]

Because the methyl group of amphetamine can be attached to the side chain in a left- or right-handed manner, amphetamine exists in two different mirror-image forms, or stereoisomers.  One of these, the right-handed or dextro-isomer, is far more biologically active than the left-handed or levo-isomer.  It is referred to as ‘D-amphetamine’ (also S(+)amphetamine, dexamphetamine, dexedrine).[1]

There are many variants of the basic chemical structure of amphetamine. Of particular interest here is that addition of a second methyl group to the basic nitrogen of the side chain leads to methamphetamine, which has even more potent biological actions (see chemical structure on the right).  Again, the dextro-isomer (d-methamphetamine) is the more powerful [1], and it is the isomer most often distributed illicitly in the United States.[2]

Pharmaceutical companies have developed compounds similar to amphetamine (e.g., methylphenidate, diethylproprion, phentermine, and fenproporex) that are used as medicines for appetite suppression, or to help treat problems such as Attention Deficit Hyperactivity Disorder (ADHD).  American chemists Ann and Alexander Shulgin described 179 different synthetic phenylethylamines, many of which they personally tested to determine effects.  Their results are presented in the book Pihkal.[3]

 

References

  • (1) Iversen L. Speed, Ecstasy, Ritalin: The Science of Amphetamines. 1 ed. London, UK: Oxford University Press; 2006.
  • (2) Mendelson J, Uemura N, Harris D, Nath RP, Fernandez E, Jacob P, III, et al. Human pharmacology of the methamphetamine stereoisomers. Clinical Pharmacology and Therapeutics 2006 Oct;80(4):403-20.
  • (3) Shulgin AT, Shulgin A. PIHKAL: A Chemical Love Story ("Phenylethylamines I Have Known and Loved"). Berkeley: Transform Press; 1991.

IllustrationsIllustrations

  • ="Structure
    Structure of Amphetamine
  • ="Structure
    Structure of Methamphetamine
  • ="Structure
    Structure of Phenethylamine