During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4’-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analogue. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the (±)-cis isomer that also appeared to be involved in at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem and high-resolution mass spectrometry, liquid and gas chromatography and nuclear magnetic resonance spectroscopy. For the work described here, both the (±)-cis and (±)-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes. (±)-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6 ± 1.1 nM (DAT), 26.9 ± 5.9 nM (NET) and 18.5 ± 2.8 nM (SERT), respectively. A comparison with d-amphetamine, aminorex and (±)-cis-4-MAR revealed that activity at SERT varied more than 100-fold across the four drugs, with (±)-cis-4,4’-DMAR exhibiting the highest potency for releasing 5-HT. The potent releasing activity of (±)-cis-4,4’-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants.

Mephedrone (4-methylmethcathinone) is the beta-keto analogue of 4-methylmethylamphetamine. Before its control in April 2010, it became popular as a legal high in the United Kingdom, displacing methylenedioxymethylamphetamine as the stimulant drug of choice. The drug has stimulant and psychoactive properties, and therefore has forensic significance in criminal and morbid toxicology. The purpose of this study was to survey casework involving the drug (impaired driving and sudden death). The cases were received in the laboratory for analysis between late 2009 and the end of 2010. Analysis of blood samples for mephedrone was conducted by liquid chromatography-mass spectrometry (LC-MS). Routine screening for alcohol and a range of other pharmaceuticals and drugs of abuse was conducted using a combination of enzyme-linked immunoassay, gas chromatography (GC) headspace, GC-MS and high-performance liquid chromatography with diode array detection. Mephedrone was detected in a total of 12 fatal cases. Most of these cases involved death by mechanical means; in two cases, death was attributed directly to mephedrone intoxication (blood concentrations of 2.1 and 1.94 mg/L). Mephedrone was detected in a total of 32 impaired driving cases. Blood concentrations ranged up to 0.74 mg/L (mean 0.21, median 0.10). The casework evidence in this study indicated that recreational use of the drug can produce to blood levels as high as 0.74 mg/L, although the most common value encountered is likely to lie between 0.2 and 0.3 mg/L.

No abstract

2,5,-Dimethoxy-4-bromoamphetamine (DOB) is of particular interest among the various "ecstasy" variants because there is an unusually long delay between consumption and effect, which dramatically increases the danger of accidental overdose in users. Screening for DOB in tablets is problematic because it is pharmacologically active at 0.2-3 mg, which is c. 50 times less than 3,4-methylenedioxy-N-methylamphetamine (MDMA) and makes it more difficult to detect in seized tablets using conventional spot tests. The normal Raman spectra of seized DOB tablets are dominated by the bands of the excipient with no evidence of the drug component. Here we report the first use of on-tablet surface-enhanced Raman spectroscopy (SERS) to enhance the signal from a low concentration drug. Raman studies (785-nm excitation) were carried on series of model DOB/lactose tablets (total mass c. 400 mg) containing between 1 mg and 15 microg of DOB and on seized DOB tablets. To generate surface-enhanced spectra, 5 microL of centrifuged silver colloid was dispensed onto the upper surface of the tablets, followed by 5 microL of 1.0 mol/dm(3) NaCl. The probe laser was directed onto the treated area and spectra accumulated for c. 20 sec (10 sec x 2). It was found that the enhancement of the DOB component in the model tablets containing 1 mg DOB/tablet and in the seized tablets tested was so large that their spectra were completely dominated by the vibrational bands of DOB with little or no contribution from the unenhanced lactose excipient. Indeed, the most intense DOB band was visible even in tablets containing just 15 microg of the drug. On-tablet surface-enhanced Raman spectroscopy is a simple method to distinguish between low dose DOB tablets and those with no active constituent. The fact that unique spectra are obtained allows identification of the drug while the lack of sample preparation and short signal accumulation times mean that the entire test can be carried out in <1 min.

A fatal case attributed to amlodipine intoxication is presented. The deceased was a 15-year-old girl who allegedly ingested 14 10-mg Istin tablets. Amlodipine concentration in peripheral blood was determined (2.7 mg/L) and was compared with published therapeutic and toxic data for amlodipine and some other dihydropyridine calcium channel-blocking agents. Amlodipine concentrations in liver, blood, and stomach contents were also determined.