Benzylpiperazine

Benzylpiperazine (BZP) is a recreational drug with euphoriant and stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity and seizures. No deaths have been reported following a sole ingestion of BZP, although there have been at least two deaths from the combination of BZP and MDMA. Its sale is banned in several countries, including Australia, Canada, New Zealand, the United States, the Republic of Ireland, the United Kingdom, Bulgaria, Romania and other parts of Europe. It is often claimed that BZP was originally synthesized as a potential antihelminthic (anti-parasitic) agent for use in farm animals. However, there are some references to BZP in medical literature that predate interest in piperazines as antihelminthics. Even so, the majority of the early work with the piperazines were investigations into their potential use as antihelminthics with the earliest clinical trials in the literature relating to piperazine being articles in the British Medical Journal in the 1950s. It was discovered that BZP had side effects and was largely abandoned as a worm treatment. It next appears in the literature in the 1970s when it was investigated as a potential antidepressant medication, but rejected when research reported that BZP had amphetamine-like effects and was liable to abuse. The study suggested that BZP “should be placed under statutory control similar to those regulating the use of amphetamine.” In the early 1990s, the United States Drug Enforcement Administration noted the drug was being used recreationally in California. It also reported that BZP was being used as an adulterant in illicit drugs. Not long after, there was an explosion in the drug's use worldwide – a situation which was soon followed by legislative control in many countries. Since 1999, benzylpiperazine use grew sharply in New Zealand due to an initial complete lack of regulation. The New Zealand government attempted to ban the product as of 18 December 2007, but the necessary second reading of the bill did not happen in time for the law to be passed. It was so widely used that an estimated 5 million pills were sold in New Zealand in 2007.Piperazine-based stimulants began to appear in Europe in 2000 but remained virtually unavailable in the rest of the world until recently. In early 2006, pills containing the active ingredients BZP and TFMPP began to appear in the city of Vancouver, British Columbia, Canada, where they first gained popularity with late night party-goers as a purported safer alternative to many of the illicit street drugs commonly available there. In 2007 piperazine based party-pill formulations started to become widely available nationwide which has caused concern with local authorities such as Health Canada and subsequently BZP has gained much media attention in 2008. In the United States, it is still used as an adulterant in ecstasy mimic tablets. BZP is a piperazine derivative which comes as either the hydrochloride salt or a free base. The hydrochloride salt is a white solid while the base form is a slightly yellowish-green liquid. BZP base is corrosive and causes burns. In countries where its purchase is legal, BZP products are often produced in small specialist laboratories. The raw materials can be purchased from various chemical supply agencies and formed into tablets or capsules using relatively cheap production techniques. The resulting product can be marketed at extremely high markup, so end-user prices can be as high as 300 times the bulk cost of raw ingredients. BZP is often marketed ostensibly as a 'dietary supplement' to avoid meeting stricter laws that apply to medicines and drugs, despite the fact that BZP has no dietary value. As of late 2005, the Misuse of Drugs Act ensured it can no longer be classified or marketed as a dietary supplement in New Zealand. Some retailers claim that BZP is a 'natural' product, describing it as a 'pepper extract' or 'herbal high,' when in fact the drug is entirely synthetic, and has not been found to occur naturally. BZP has been shown to have a mixed mechanism of action, acting on the serotonergic and dopaminergic receptor systems in a similar fashion to MDMA. BZP has amphetamine-like actions on the serotonin reuptake transporter, which increase serotonin concentrations in the extracellular fluids surrounding the cell and thereby increasing activation of the surrounding serotonin receptors. BZP has a lower potency effect on the noradrenaline reuptake transporter and the dopamine reuptake transporter. BZP has a high affinity action at the alpha2-adrenoreceptor, it is an antagonist at the receptor, like yohimbine, which inhibits negative feedback, causing an increase in released noradrenaline. BZP also acts as a non-selective serotonin receptor agonist on a wide variety of serotonin receptors; binding to 5HT2A receptors may explain its mild hallucinogenic effects at high doses, while partial agonist or antagonist effects at the 5HT2B receptors may explain some of BZPs peripheral side effects, as this receptor is expressed very densely in the gut, and binding to 5HT3 receptors may explain the common side effect of headaches, as this receptor is known to be involved in the development of migraine headaches.