'Designer drugs'. A problem in clinical toxicology
Buchanan JF, Brown CR.
San Francisco Regional Poison Control Center,
San Francisco General Hospital,
University of California.
Med Toxicol Adverse Drug Exp 1988 Jan-Dec;3(1):1-17


'Designer drugs' are substances intended for recreational use which are derivatives of approved drugs so as to circumvent existing legal restrictions. The term as popularised by the lay press lacks precision. Contrary to the popular belief that 'designer drugs' are original creations, the majority of these agents are 'borrowed' from legitimate pharmaceutical research. They merely represent the most recent developments in the evolution of mind-altering chemicals. The most extensively studied class of psychoactive compounds is the phenylethylamines (mescaline analogues). This class includes catecholamines, therapeutic agents and numerous illicit derivatives. Subtle alterations of the phenylethylamine molecule give rise to a spectrum of pharmacological properties ranging from pure sympathomimetic stimulation to primarily psychoactive effects. Although most of these compounds are only of historical interest, amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) continue to be used recreationally. Many deaths have been ascribed to this class of compounds. In overdose the differences between these compounds blur and the clinical presentation is similar to that of amphetamine overdose characterised by tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis, agitation, muscle rigidity, and hyper-reflexia. Death usually results from arrhythmias, hyperthermia or intracerebral haemorrhage. Treatment is aggressive and supportive with careful attention to temperature, blood pressure and seizure control. Synthetic opioid derivatives, which represent the second major class of 'designer drugs', are derivatives of fentanyl (e.g. alpha-methylfentanyl, 3-methylfentanyl) or pethidine (meperidine) and are extremely potent compounds responsible for numerous overdose deaths. Attempts to synthesise pethidine have resulted in the accidental production of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a compound which is metabolised in the brain by the monoamine oxidase system to a toxic intermediate (MPP+) which selectively destroys the sustantia nigra, resulting in the rapid onset of severe Parkinsonian symptoms. Naloxone will antagonise the opiate effects of this drug class, although high doses may be required. Arylhexylamines constitute the third class of 'designer drugs'. The predominant member of this class is phencyclidine (PCP), a derivative of the anaesthetic ketamine. This unique class of psychoactive agents exhibits broad and complex pharmacological effects.
Opioid receptors
Meperidine: structure
MPP+ and Parkinsonism
Toxic meperidine analogs
MPTP, MPP+ and permanent Parkinsonism

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