Examination of Firearms Review: 2007 to 2010 - Interpol

2.4 Emergence of New Drugs of Abuse
There is increasing use of legally available “designer drugs” as recreational
drugs. Many of these designer drugs are structurally and/or pharmacologically
very similar to their corresponding illicit analogs. Contrary to new medications,
which are extensively studied in animals, followed by human epidemiological
investigations and risk assessment under controlled clinical environments,
many designer drugs are consumed without any safety testing.
2.4.1 Phenethylamines
Metabolite standards are often not commercially available, particularly in the
case of new designer drugs. As an alternative to often cumbersome chemical
synthesis, human cytochrome P450 isoenzymes (P-450s) can be used for the
biotechnological synthesis of drug metabolites. This concept was applied to
the synthesis of N-(1-phenylcyclohexyl)-2-hydroxyethanamine (PCHEA), the
common O-dealkyl metabolite of the designer drugs
N-(1-phenylcyclohexyl)-2-methoxyethanamine (PCMEA) and
N-(1-phenylcyclohexyl)-2-ethoxyethanamine (PCEEA) [150]. The involvement
of P450s in the metabolism of N-(1-phenylcyclohexyl)-3-ethoxypropanamine
(PCEPA) and N-(1-phenylcyclohexyl)-3-methoxypropanamine (PCMPA), to
the common metabolite N-(1-phenylcyclohexyl)-3-hydroxypropanamine
(PCHPA), was studied [151]. Among the tested isoenzymes, P450 2B6, 2C19,
2D6, and 3A4 catalyzed PCEPA O-deethylation, and P450 2B6, 2C19, and
2D6 catalyzed PCMPA O-demethylation.
Another new class of designer drugs, the so-called beta-keto (bk)
phenethylamines (aka “cathinones”) such as mephedrone
(bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone
(bk-MDMA) have appeared in the illicit drug markets in many countries. The
metabolites of bk-MBDB and
2-ethylamino-1-(3,4-methylenedioxyphenyl)propan-1-one (bk-MDEA) in
human urine were identified using synthesized standards [152]. Based on
GC-MS and LC-MS, N-dealkylation, demethylenation followed by
O-methylation, and β-ketone reduction were identified as their major metabolic
pathways.
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