Benzylpiperazine Research Articles

Design and development of benzyl piperazine linked 5-phenyl-1,2,4-triazole-3-thione conjugates as potential agents to combat Alzheimer’s disease

Our present work demonstrates the molecular hybridization-assisted design, synthesis, and biological evaluation of 22 benzylpiperazine-linked 1,2,4-triazole compounds (PD1-22) as AD modifying agents. All the compounds were tested for their in vitro hChEs, hBACE-1, and Aβ-aggregation inhibition properties. Among them, compound PD-08 and PD-22 demonstrated good hChE and hBACE-1 inhibition as compared to standards donepezil and rivastigmine. Both compounds displaced PI from PAS at 50 µM concentration which was comparable to donepezil and also demonstrated anti-Aβ aggregation properties in self- and AChE-induced thioflavin T assay. Both compounds have shown excellent BBB permeation via PAMPA-BBB assay and were found to be non-neurotoxic at 80 µM concentration against differentiated SH-SY5Y cell lines. Compound PD-22 demonstrated an increase in rescued eye phenotype in Aβ-phenotypic drosophila AD model and amelioration of behavioral deficits in the Aβ-induced rat model of AD. The in-silico docking studies of compound PD-22 revealed a good binding profile towards CAS and PAS residues of AChE and the catalytic dyad of the BACE-1. The 100 ns molecular dynamics simulation studies of compound PD-22 complexed with AChE and BACE-1 enzymes suggested stable ligand-protein complex throughout the simulation run. Based on our findings compound PD-22 could further be utilized as a lead to design a promising candidate for AD therapy

Novel synthesis naringenin-benzyl piperazine derivatives prevent glioblastoma invasion by inhibiting the hypoxia-induced IL6/JAK2/STAT3 axis and activating caspase-dependent apoptosis

• A series of N -benzyl piperazine derivatives of naringenin (8 compounds) were synthesized. • The anti-proliferative effect of all eight synthesized compounds was determined in GBM cells. • Two compounds with low IC50 values were selected for molecular studies to determine their mechanisms of action. • The anti-invasion effects of two selected compounds on GBM tumor spheroids were investigated using hypoxia, JAK/STAT, and apoptosis signaling pathways. • NDs exert a strong anti-invasion effect via inhibiting the hypoxia-induced IL6/JAK2/STAT3 axis and inducing caspase-dependent mitochondrial apoptosis.

Synthesis Characterization and Antibacterial Activity of Terazosin Hydrochloride Drug and Market Formulation

Terazosin hydrochloride is an anti-hypertensive drug which is used to treat the diseases of hypertension. The literature survey shows the proposed synthesis of Terazosin hydrochloride derived from the starting material of 2-chloro-6, 7-dimethoxy–quinazoline-4-amine in the presence of 2-methoxy ethanol with n- benzyl piperazine to form the product. The Terazosin derivatives were prepared with the help of literature survey were 1, 4-bis-(furan-2-yl-carbonl) piperazine, 1, 4-bis-(tertrahydrofuran-2-yl) carbonyl piperazine, and 1-(4-amino-6, 7-dimethoxy- quinazoline-2-yl)- 4-formyl- piperazine were prepared by maintaining environmental condition. The characterization done for prepared derivative was done through 1H-NMR, MASS and IR Spectroscopy. The antibacterial activity of prepared derivatives was performed on the various bacteria like E. coli, Pseudomonas aeruginosa, Shigella sonneii, Klebsiella pneumonia, Staphylococcus aureus, Shigella flexneri, Vibrio cholera, Bacillus subtilis, Pseudomonas fluorescens, Pseudomonas aeruginosa, Staphylococcus aureus. The desired derivatives shown maximum zone of inhibition using concentration prepared 100µg and 200µg using standard drug. The derivatives that shows maximum inhibition 6, 7-dimethoxy-2-piperazine-1-yl-quinazoline -4-amine and minimum was shown by 1, 4-bis-(furan-2-yl-carbonl) piperazine, 1,4-bis-(tertrahydrofuran- 2-yl) carbonyl piperazine. The result should that prepared Terazosin derivatives shows potent actively when compared with standard ciprofloxacin.

Voltammetric profiling of new psychoactive substances: Piperazine derivatives

The emergence of a large number of new psychoactive substance (NPS) on the global drug market poses a significant risk to public health and a challenge to drug control systems. Over the last decades, electrochemical sensing of illicit drugs has experienced a very significant growth, since these techniques can provide fast, portable, sensitive and low-cost detection alternatives for the analysis of drugs, metabolites and/or transformation products in different matrices. To understand and clarify the oxidative mechanism of piperazine designer drugs, the voltammetric profile of psychoactive piperazine derivatives 1-phenylpiperazine (PhPIP), 3-chlorophenylpiperazine (mCPP), 3-trifluoromethylphenylpiperazine (TFMPP), 4-fluorophenylpiperazine (pFPP) and benzylpiperazine (BZP) has been investigated at a glassy carbon electrode. The data found showed the crucial role of the aromatic amine, present in PhPIP, mCPP, pFPP and TFMPP molecular’ structures, on the oxidative profiles. The voltammetric behavior of BZP is quite different from those found for the other piperazines under study due to the nature of the amine group present in BZP molecular’ structure, benzylic instead of an aromatic amine. This work can be a helpful contribution to the ability to predict and identify metabolites and the development of new analytical approaches that can allow the rapid and specific quantitative detection of psychoactive piperazine derivatives.

Electrochemical determination of novel psychoactive substances by differential pulse voltammetry using a microcell for boron-doped diamond electrode and screen-printed electrodes based on carbon and platinum

25B-NBOMe, benzylpiperazine (BZP), 1-(3-chlorophenyl)piperazine (mCPP), and N,N-dimethyltryptamine (DMT) are potent hallucinogenic and stimulant drugs which have emerged as novel psychoactive substances (NPS). The electroanalytical behavior of these compounds was investigated by differential pulse voltammetry (DPV) on boron-doped diamond (BDD) electrode assembled in a homemade microcell, and disposable screen-printed electrodes based on bare carbon (SP-C) and platinum (SP-Pt). The low-cost micro-method proposed in this paper requires volume ranging from 50 μL to 100 μL, minimal sample preparation, and generates very few residues. The electrochemical screening exhibited anodic peaks studied by linear regression of five-point analytical curves (n = 3) which allowed for estimating the sensitivity, limits of detection (LOD) and quantification (LOQ), repeatability (Sr), and intermediate precision (SRW). These results translate into methods with high sensitivity, satisfactory precision (range of 1.7% to 9.0%) and low limits of detection (LOD from 0.15 μg/mL to 1.8 μg/mL) with analytical value in clinical and forensic techniques. Accuracy and applicability of the voltammetric method was assessed in spiked oral fluid samples by standard additions calibration curves with recovery ranging from 98% to 103%. For the first time, the electrochemical data obtained by DPV on three different working electrodes and the analytical parameters are compared for these NPS.

Design, synthesis, and biological evaluation of quinazoline derivatives containing piperazine moieties as antitumor agents

A series of novel quinazoline derivatives containing piperazine analogs are synthesized via substitution reactions with 6,7-disubstituted 4-chloroquinazoline and benzyl piperazine (amido piperazine). Potent antiproliferative activities are observed against A549, HepG2, K562, and PC-3 with N-(3-chlorophenyl)-2-(4-(7-methoxy-6-(3-morpholino-propoxy)quinazoline-4-yl)piperazine-1-yl)acetamidename C9 showing excellent activity. This active derivative was screened for cell migration ability, proliferation effects, and apoptosis against A549 and PC-3 cells, with the result showing biological activity almost equal to that of the control gefitinib.

New classes of carbazoles as potential multi-functional anti-Alzheimer’s agents

Multi-Target approach is particularly promising way to drug discovery against Alzheimer's disease. In the present study, we synthesized a series of compounds comprising the carbazole backbone linked to the benzyl piperazine, benzyl piperidine, pyridine, quinoline, or isoquinoline moiety through an aliphatic linker and evaluated as cholinesterase inhibitors. The synthesized compounds showed IC50 values of 0.11–36.5 µM and 0.02–98.6 µM against acetyl- and butyrylcholinesterase (AChE and BuChE), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 3s could bind effectively to the peripheral anionic binding site (PAS) and anionic site of the enzyme with mixed-type inhibition. Compound 3s was the most potent compound against AChE and BuChE and showed acceptable inhibition potency for self- and AChE-induced Aβ1-42 aggregation. Moreover, compound 3s could significantly protect PC12 cells against H2O2-induced toxicity. The results suggested that the compounds 3s could be considered as a promising multi-functional agent for further drug discovery development against Alzheimer's disease.

Synthesis, computational molecular docking analysis and effectiveness on tyrosinase inhibition of kojic acid derivatives

Tyrosinase inhibitors have become increasingly important as whitening agents and for the treatment of pigmentary disorders. In this study, the synthesis of kojic acid derivatives having 2-substituted-3-hydroxy-6-hyroxymethyl/chloromethyl/methyl/morpholinomethylpiperidinyl- methyl/pyrrolidinylmethyl-4H-pyran-4-one structure (compounds 1–30) with inhibitory effects on tyrosinase enzyme were described. One-pot Mannich reaction was carried out by using kojic acid/chlorokojic acid/allomaltol and substituted benzylpiperazine derivatives in presence of formaline. Subsequently, cyclic amine (morpholine, piperidine and pyrrolidine) derivatives of the 6th-position of chlorokojic acid were obtained with nucleophilic substitutions in basic medium. The structures of new compounds were identified by FT-IR, 1H- and 13C NMR, ESI-MS and elemental analysis data. The potential mushroom tyrosinase inhibitory activity of the compounds were evaluated by the spectrophotometric method using l-DOPA as a substrate and kojic acid as the control agent. The potential inhibitory activity was also investigated in silico using molecular docking simulation method. Tyrosinase inhibitory action was significantly more efficacious for several compounds (IC50: 86.2–362.1 µM) than kojic acid (IC50: 418.2). Compound 3 bearing 3,4-dichlorobenzyl piperazine moiety was proven to have the highest inhibitory activity. The results of docking studies showed that according to the predicted conformation of compound 3 in the enzyme binding site, hydroxymethyl group provides a metal complex with copper ions and enzyme. Thus, this interaction explain the high inhibitory activities of the compounds 1, 3 and 4 possessing hydroxymethyl substituent supporting the mushroom assay results with docking studies. In accordance with the results, it is suggested that Mannich bases of kojic acid bearing substituted benzyl piperazine groups (compounds 1, 3, 4, 11, 13, 14, 23, 24, 28, and 29) could be promising antityrosinase agents. Additionally, considering the relationship between tyrosinase inhibitory activity results and molecular docking, a new tyrosinase inhibition mechanism can be proposed.

Synthetic Small Molecule Characterization and Isomer Discrimination Using Gas-Phase Hydrogen–Deuterium Exchange IMS-MS

Ion mobility spectrometry-mass spectrometry (IMS-MS) combined with gas-phase hydrogen-deuterium exchange has been used to characterize novel psychoactive substances (NPSs) which are small synthetic compounds designed to mimic the effects of other illicit substances. Here, NPSs containing labile heteroatom hydrogens were evaluated for HDX reactivity in the presence of either deuterated water (D2O) or ammonia (ND3) within the drift tube. An initial evaluation of exchange propensity was performed for six NPSs. Five compounds exchanged in the presence of ND3 while only one NPS (benzyl piperazine) exchanged with D2O. The exchange mechanism of D2O requires stabilization with a nearby charged site; the diamine ring of benzyl piperazine provided this charge site at a fixed length. Three disubstituted benzene isomers ( o-, m-, and p-fluorophenyl piperazine) containing the diamine ring structure and a fluorine atom were subsequently analyzed. Having identical isotopic composition and nearly identical drift time distributions, these isomers could not be distinguished by IMS-MS alone. However, upon undergoing HDX in the drift tube, a t test of means (α = 0.05) showed that discrimination was possible if the exchange data from both reagent gases were included. Molecular dynamics simulations show that the proximity of the fluorine to the diamine ring hinders the dihedral angle rotation between the benzene and the diamine ring; this may partially account for the observed exchange differences.

Benzylpiperazine (BZP) additively increases Methylenedioxymethamphetamine (MDMA) cardiotoxicity in H9c2 cells, an effect potentiatted by hyperthermia

Benzylpiperazine (BZP) additively increases Methylenedioxymethamphetamine (MDMA) cardiotoxicity in H9c2 cells, an effect potentiatted by hyperthermia

Extending the capability of forensic electrochemistry to the novel psychoactive substance benzylpiperazine

Benzylpiperazine (BZP) is a novel psychoactive substance that is commonly abused in tablet form as an “ecstasy-type” drug. Electroanalysis offers genuine potential for field testing of bulk drug samples. This research is the first to investigate the viability of voltammetric analysis of BZP. Initial cyclic voltammetry in 0.1M KCl showed an oxidative peak at a glassy carbon electrode for BZP at approximately 0.8V (scan rate 205mVs−1). Next an optimised electrode/electrolyte combination (viz. 80:20W:W glassy carbon beads:nujol and pH9.5, 40mM, Britton-Robinson buffer) was developed using K3Fe(CN)6 to test the electrode material. The oxidation of BZP involves two electrons and two protons and a mechanism has been proposed. An anodic stripping square wave voltammetric method was optimised by factorial design with the conditions of deposition: −0.8V for 135s, and stripping: step height 10mV, amplitude 50mV and frequency 13Hz. A limit of detection of 6μM was achieved. The resolution against 3,4-methylenedioxymethylamphetamine (MDMA) was also verified.

Occurrence of new psychoactive substances in wastewater of major Chinese cities

New psychoactive substances have become increasingly popular across the globe in recent years, which may cause certain public health issues. In this work, sewage-based epidemiology was applied to examine the use of two synthetic cathinones, mephedrone and methylenedioxypyrovalerone (MDPV), and three piperazines, benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), and 1-(3-Chlorophenyl)piperazine (mCPP), across China. Influent wastewater samples were collected from 36 sewage treatment plants (STPs) in 18 major cities that cover all the geographic regions of the country. Effluent samples were also collected from selected STPs to determine removal rates. Mephedrone, TFMPP, and mCPP were below detection limits in all the wastewater samples collected, indicating negligible use of these substances in China. MDPV was detected in wastewater at 13 STPs. However, its loads were <1mg/1000inh/d at most of these STPs, indicating low use of this substance. BZP was detected at all the STPs examined, with loads typically falling within the range of 3–10mg/1000inh/d. No clear geographic pattern in BZP occurrence in wastewater was identified. Since BZP in wastewater may also come from its legal sources, whether widespread occurrence of BZP means widespread abuse is yet to be confirmed. Apparent removal of MDPV by wastewater treatment was low (<25%), whereas removal of BZP was nearly complete (typically>95%).

Temporal trends in drug use in Adelaide, South Australia by wastewater analysis

Analysis of municipal wastewater for drug metabolites can reveal the scale of drug use within communities. An Australian city with a population of 1.2million inhabitants was assessed for 4 stimulants: cocaine, methamphetamine, 3.4-methylenedioxymethamphetamine (MDMA) and amphetamine; 6 opioids: codeine, morphine, heroin, fentanyl, oxycodone and methadone; 11 new psychoactive substances (NPS); benzylpiperazine (BZP), trifluoromethylphenylpiperazine (TFMPP), methcathinone, methylone, mephedrone, methylenedioxypyrovalerone (MDPV), alpha pyrrolidinopentiophenone (alpha-PVP), paramethoxyamphetamine (PMA), 25C-NBOMe, 25B-NBOMe, 25I-NBOMe; and cannabis, for up to four years between December 2011 and December 2015. Temporal trends revealed increasing usage rates of methamphetamine, cocaine, oxycodone, and fentanyl, while decreasing rates of use were observed for MDMA, BZP and methylone. Use of other opioids and cannabis was generally stable across years, while use of new psychoactive substances fluctuated without an apparent direction. Opioids and cannabis were used at a consistent level through the course of the week, while use of stimulants and some NPS increased on the weekend. Seasonal differences in use were observed for MDMA and cannabis (p$_amp_$lt;0.05) where, on average, MDMA use was approximately 90% higher in December than in other months and cannabis use was approximately 45% lower in each February. Residual month-to-month variability measures on trend-free data showed NPS use had higher variability than the stimulants and opioids. Frequent wastewater sampling and analysis over prolonged periods has yielded valuable insights into long-term drug use trends, in some instances revealed important within-year trends, and demonstrated the differing patterns of use of drugs on weekends compared to weekdays.

Using fMRI to compare the effects of benzylpiperazine with dexamphetamine — Their differences during the Stroop paradigm

Benzylpiperazine (BZP) has been found to increase neural activation in the dorsal striatum when compared to placebo in response to a Stroop paradigm, in addition, subjective effects have been compared to dexamphetamine (DEX). Despite their similarities, the two have not been directly compared in respect to their effects on selective attention and inhibition. To use a double-blind placebo-controlled crossover study to compare the acute effects of BZP and DEX on executive function using functional magnetic resonance imaging (fMRI) and an event-related Stroop task. Eleven healthy participants aged 18-40 years undertook the Stroop task 90[Formula: see text]min after taking an oral dose of either BZP (200[Formula: see text]mg), DEX (20[Formula: see text]mg) or placebo. BZP induced a greater increase in activation than DEX in the inferior frontal gyrus (IFG) during the Stroop task. DEX increased BOLD signal in the thalamus and decreased it in the IFG in comparison to placebo. Despite BZP and DEX reportedly inducing similar subjective effects, there are different patterns of neural activation. We believe this differential activity is due to pharmacological differences in their receptor binding profiles and that subsequent inhibitory effects might be due to their direct effect on dopaminergic activity.

Mixtures of benzylpiperazine (BZP) and 3-trifluoromethylphenylpiperazine (TFMPP) elicit hepatotoxic effects in human HepaRG cells and primary rat hepatocytes

Mixtures of benzylpiperazine (BZP) and 3-trifluoromethylphenylpiperazine (TFMPP) elicit hepatotoxic effects in human HepaRG cells and primary rat hepatocytes

Structure-dependent inhibition of the human α1β2γ2 GABAA receptor by piperazine derivatives: A novel mode of action

Piperazine derivatives are a class of psychoactive substances applied in prescription medicines like antidepressants as well as in drugs of abuse. They are known to increase brain levels of catecholamines, likely via reversal of reuptake transporters. However, other mechanisms could also contribute to increased neurotransmitter levels, e.g., reduced inhibitory inputs on catecholaminergic neurons.Inhibition of the main inhibitory input in the brain, the GABAergic system, by piperazine derivatives could contribute to increased neurotransmitter levels. Our previous studies support this by demonstrating that 1-(3-chlorophenyl)piperazine (3CPP/mCPP) is an antagonist of the human α1β2γ2 GABAA receptor (GABAA-R). We therefore investigated the effect of 12 additional piperazine derivatives on the function of the human α1β2γ2 GABAA-R expressed in Xenopus oocytes, using the two-electrode voltage-clamp technique. Tested derivatives included benzylpiperazine (BZP), methylbenzylpiperazines (2/3MBP), phenylpiperazine (PP), methoxyphenylpiperazines (2/3/4MPP/MeOPP), chlorophenylpiperazines (2/4CPP) and fluorophenylpiperazines (4FPP/TFMPP).All derivatives concentration-dependently inhibited the GABA-evoked ion current. Chlorophenylpiperazines were the most potent GABAA-R antagonists; the IC20 value for 1-(2-chlorophenyl)piperazine (2CPP) was 46μM and 2CPP induced a maximum inhibition of ∼90% at 1mM. Derivatives can be ranked as follows from highest to lowest potency based on IC20 values: 2CPP>3MPP>4CPP>4MPP>2MBP>3CPP>PP>4FPP>2MPP>TFMPP>3MBP>BZP.This study demonstrates a novel mode of action of piperazine derivatives, i.e., antagonism of the GABAA-R. This mechanism can result in increased catecholamine levels that indirectly contribute to toxicity, e.g., adverse effects during overdoses. Therefore, this important mode of action is not only relevant for therapeutic psychiatric interventions, but could also proof valuable for therapeutic interventions in intoxications.

Acute effects of the designer drugs benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) using functional magnetic resonance imaging (fMRI) and the Stroop task--a pilot study.

A novel group of designer drugs containing benzylpiperazine (BZP) and/or trifluoromethylphenylpiperazine (TFMPP) have been available worldwide for more than a decade; however, their effects on human brain function have not been extensively described. In a double-blind, placebo-controlled crossover study, the acute effects of BZP and TFMPP (alone and in combination) on the neural networks involved in executive function were investigated using an event-related Stroop functional magnetic resonance imaging (fMRI) paradigm. Thirteen healthy participants aged 18-40 years undertook the Stroop task 90 min after taking an oral dose of either BZP (200 mg), TFMPP (either 50 or 60 mg), BZP + TFMPP (100 + 30 mg) or placebo. A change in activity in neural regions reflects an increase in local demand for oxygen, due to an increase in neuronal activity. Relative to placebo, an increase in neural activation was observed in the dorsal striatum following BZP, and in the thalamus following TFMPP, when performing the Stroop task. These data suggest that additional compensatory resources were recruited to maintain performance during the Stroop task. When BZP and TFMPP were administered together, both the dorsal striatum and thalamus were activated. However, the combination of BZP/TFMPP attenuated activation in the caudate, possibly due to TFMPP's indirect effects on dopamine release via 5HT2C receptors.

Isotopic profiling of seized benzylpiperazine and trifluoromethylphenylpiperazine tablets using δ13C and δ15N stable isotopes

This paper demonstrates the use of isotopic analysis of 23 benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) containing tablets seized on two independent occasions by the Northern Territory (NT) Police, Australia. Isolation (High Performance Liquid Chromatography (HPLC)) of BZP and TFMPP followed by Isotope Ratio Mass Spectrometry (IRMS) (carbon and nitrogen stable isotopes) analysis was performed. Results are presented for δ13C and δ15N values of the respective piperazine analogues. The isotopic data and statistical analysis suggest a common source of manufacture for the BZP samples but suggest different sources for the TFMPP isolated from the corresponding BZP containing tablets investigated. The use of IRMS in this case study demonstrated the ability to obtain information regarding the BZP/TFMPP sources unattainable via conventional chemical analysis.

New psychoactive substances: issues about the new approach from New Zealand government.

The regulation of new psychoactive substances (NPS) is a challenge for governments throughout the world. Different approaches have been used to address the problem, although most forbid their use. In July 2013, the New Zealand government proposed a new NPS regime which placed the onus onto manufacturers to prove that their products pose a low risk of harm, prior to receiving approval. One positive aspect of this proposal is that more information will be gathered before the government makes the decision of whether to allow or forbid an NPS. Lack of data on the safety or danger of NPS has led governments to make decisions that are not based on scientific evidence 1. The paper by Wilkins 2 identifies important questions about this new approach, although additional issues were also noted. The first issue is related to whether the manufacturers of NPS will submit their drugs for approval. When considering the high application fee, the huge costs and long time required for clinical trials, and the need to conduct the entire protocol for each final product, the process will probably be extremely expensive and time-consuming. Additionally, in recent decades, NPS manufacturers have attempted to circumvent law and drug regulations. For example, many NPS are created by introducing slight modifications into the chemical structure of controlled substances 3. Is it expected that these same manufacturers will wait years and spend a great deal of money in an attempt to legalize their products? This great difficulty in legalizing a substance may have a similar impact to its restriction. The second issue is whether clinical trials will properly evaluate NPS. As noted by Wilkins, some important aspects, such as high consumption episodes, polydrug use, use by vulnerable populations, high-risk modes of administration and long-term adverse effects, will most probably not be assessed by these studies 2. Moreover, as a therapeutic effect is not the aim, the dosage of the product tested may be the lowest possible in an attempt to mask potential side effects. What will be the sample size of such clinical trials? Small samples are not sufficiently robust to detect even less rare adverse effects. Even so, is it ethical to conduct a clinical trial with a product that has potential harm and no clear benefit? The third issue that is central to this discussion is the purpose of legalizing an NPS with no therapeutic effect. Some argue that such drugs could substitute for more dangerous drugs and reduce their use 4. However, there is no scientific evidence in support of this argument. In New Zealand, from 2005 to 2008, benzylpiperazine (BZP) party-pills were legally available for purchase, although subject to regulations 5. The impact that this ‘legal status’ had on young people was to indicate that it was safe and socially acceptable, suggesting that they could take more pills 5. The argument that prohibition enhances organized crime also does not appear to be very consistent. For example, the ecstasy and marijuana markets have little connection with organized crime 1. However, prohibition reduces the possibility of quality control and assurance of NPS. This is an emerging and complex theme with no simple solution. A longitudinal evaluation of New Zealand's approach to NPS will permit further conclusions about its applicability and usefulness in other countries. None.

The impact of the prohibition of benzylpiperazine (BZP) “legal highs” on the availability, price and strength of BZP in New Zealand

BackgroundLegal highs containing benzylpiperazine (BZP) were widely sold in New Zealand until BZP was prohibited in 2008. We examined the impact the prohibition had on the availability and price of BZP over following years. MethodsTwo national population surveys of BZP use were conducted in 2006 and 2009. Four annual targeted surveys of frequent drug users (FDU) were conducted from 2007–2010. Availability and price measures were obtained. Inflation-adjusted real retail prices were calculated. Other drug markets were monitored as quasi-controls. ResultsThe proportion of BZP users from the general population who considered the availability of BZP to be ‘very easy’ declined from 76% in 2006 to 21% in 2009. The proportion who thought BZP had become ‘harder’ to obtain increased from 5% in 2006 to 71% in 2009. The proportion who reported the price of BZP was ‘higher’ increased from 27% in 2006 to 51% in 2009. FDU who considered the availability of BZP to be ‘very easy’ declined from 98% in 2007 to 15% in 2008, and then increased to 42% by 2010. The real retail price of a BZP tablet increased from $9.86 in 2007 to $15.83 in 2010. The proportion who considered the price of BZP to be ‘increasing’ rose from 3% in 2007 to 47% in 2010. ConclusionsThe availability of BZP declined immediately following its prohibition. Availability recovered in subsequent years, but not to the pre-prohibition legal level. The price of BZP increased slowly over a number of years following the prohibition.