The emergence of new psychoactive substance (NPS) benzodiazepines: a review

The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased. Some of these benzodiazepines have only been patented, some of them have not been previously synthesised and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are new psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. The aim of this review is to collate the available information on these benzodiazepines and to provide a starting point for the further investigation of their pharmacokinetics which is clearly required

G-Protein Activation Kinetics And Spill-Over Of Gaba May Account For Differences Between Inhibitory Responses In The Hippocampus And Thalamus

We have developed a model of GABAergic synaptic transmission mediated by GABAA and GABAB receptors, including cooperativity in the G-protein cascade mediating the activation of K + channels by GABAB receptors. If the binding of several G-proteins is needed to activate the K + channels, then only a prolonged activation of GABAB receptors evoked detectable currents. This could occur if strong stimuli evoked release in adjacent terminals, and the spill-over resulted in the prolonged activation of the receptors, leading to inhibitory responses similar to those observed in hippocampal slices. The same model also reproduced thalamic GABAB responses to high-frequency bursts of stimuli. In this case, the prolonged activation of the receptors was due to high-frequency release conditions. This model provides new insights into the function of GABAB receptors in normal and epileptic discharges. INTRODUCTION Two receptor types, GABAA and GABAB , are responsible for most inhibitory synaptic pot..