Metabolism of Designer Drugs of Abuse

Abstract

Abuse of designer drugs is widespread among young people, especially in the so-called "dance club scene" or "rave scene", worldwide. Severe and even fatal poisonings have been attributed to the consumption of such drugs of abuse. However, in contrast to new medicaments, which are extensively studied in controlled clinical studies concerning metabolism, including cytochrome P450 isoenzyme differentiation, and further pharmacokinetics, designer drugs are consumed without any safety testing. This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years. Para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA) and 4-methylthioamphetamine (4-MTA), were taken into consideration as new "classical" amphetamine-derived designer drugs. Furthermore, N-benzylpiperazine (BZP), 1-(3, 4-methylenedioxybenzyl)piperazine (MDBP), 1-(3-trifluoromethylphenyl)piperazine (TFMPP), 1-(3-chlorophenyl)piperazine (mCPP) and 1-(4-methoxyphenyl)piperazine (MeOPP) were taken into consideration as derivatives of the class of piperazine-derived designer drugs, as well as alpha-pyr-rolidinopropiophenone (PPP), 4'-methoxy-alpha-pyrrolidinopropiophenone (MOPPP), 3', 4'-methylenedioxy-alpha-pyrrolidino-propiophenone (MDPPP), 4'-methyl-alpha-pyrrolidinopropiophenone (MPPP), and 4'-methyl-alpha-pyrrolidinoexanophenone (MPHP) as derivatives of the class of alpha-pyrrolidinophenone-derived designer drugs. Papers describing identification of in vivo or in vitro human or animal metabolites and cytochrome P450 isoenzyme dependent metabolism have been considered and summarized.

Investigation of the First Deaths in the United Kingdom Involving the Detection and Quantitation of the Piperazines BZP and 3-TFMPP

“…BZP was first noted as a drug of abuse in Sweden in 1999 (1,5). Although analytical and metabolic data have been published and user reports exist on various Internet forums, there have actually been no confirmed reported cases of TFMPP abuse (1,(6)(7)(8). BZP and 3-TFMPP are available in tablet or capsules via Internet-and non-lnternet-based shops, with 3-TFMPP typically only present in products that contain BZP as well (9)(10)(11).…”

Development and validation of a gas chromatography/mass spectrometry method for simultaneous quantification of benzylpiperazine and its metabolites: Application to a pilot toxicokinetic study in mice

“…It should be noted that the vast majority of these novel drugs have not been tested for their safety (lack of pharmacological and toxicological information) and, as they are not covered by any drug legislation or control, the potential health implications of their use are largely unknown and difficult to predict (2,6,7). The use of these products is normally based only in other users' opinions (2, 3) and on the market advertisement, which, usually, doesn't refer the presence of psychoactive compounds on the list of ingredients (1,3,8), adverse effects or provide safety information like contraindications and possible drug-drug interactions (2,3,9).…”

“…Most of these substances have gain popularity within the "rave" party scene (recreational drugs) among young people as alternatives to illicit drugs (7,13). Among such recreational drugs, piperazine derivatives emerged during 1990s as a completely new class of designer drugs and safe and legal alternatives to amphetamines (7).…”

“…Among such recreational drugs, piperazine derivatives emerged during 1990s as a completely new class of designer drugs and safe and legal alternatives to amphetamines (7). The first medical use of piperazine compounds was as antihelminthic agents, in 1950s, for the treatment of human and animal worm infections.…”

Designer drugs: aspectos analíticos e biológicos

“…[9][10][11][12] As primeiras designer drugs que surgiram eram narcóticas derivadas da heroína. 13,14 Depois surgiram os derivados das feniletilaminas que incluem a 2-metil-amino-3,4-metileno-dioxi--propiofenona (metilona), N-metil-1-(1,3-benzodioxol-5-il)-2--butanamina (MBDB) e a 2,5-dimetoxi-4-iodo-feniletilamina (2C-I). 15 Alguns derivados da triptamina incluem α-metil-triptamina (AMT), 5-metoxi-α-metil-triptamina (5-MeO-AMT), 5-metoxi--N,N-di-isopropil-triptamina (5-MeO-DIPT), e 5-metoxi-N,N--metil-isopropil-triptamina (5-MeO-MIPT).…”