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Methylenedioxypyrovalerone

Methylenedioxypyrovalerone is a stimulant of the cathinone class which acts as a Norepinephrine–dopamine reuptake inhibitor. It was first developed in the 1960s by a team at Boehringer Ingelheim, its activity at the dopamine transporter is six times stronger than at the norepinephrine transporter and it is inactive at the serotonin transporter. MDPV remained an obscure stimulant until around 2004 when it was sold as a designer drug; until banned in 2011, products containing MDPV and labeled as bath salts were sold as recreational drugs in gas stations and convenience stores in the United States, similar to the marketing for Spice and K2 as incense. The hydrochloride salt exists as a fine crystalline powder, its color can range from pure white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are to consist of either pyrrolidine or alpha-dibrominated alkylphenones—respectively, from either excess pyrrolidine or incomplete amination during synthesis; these impurities account for its discoloration and fishy or bromine-like odor, which worsens upon exposure to air, moisture, or bases.

Methylenedioxypyrovalerone has no record of FDA approved medical use. It has been shown to produce robust reinforcing effects and compulsive self-administration in rats, though this had been provisionally established by a number of documented cases of misuse and addiction in humans before the animal tests were carried out. MDPV is the 3,4-methylenedioxy ring-substituted analog of the compound pyrovalerone, developed in the 1960s, used for the treatment of chronic fatigue and as an anorectic, but caused problems of abuse and dependence. Other drugs with a similar chemical structure include α-pyrrolidinopropiophenone, 4'-methyl-α-pyrrolidinopropiophenone, 3',4'-methylenedioxy-α-pyrrolidinopropiophenone and 1-phenyl-2--1-pentanone. MDPV acts as a stimulant and has been reported to produce effects similar to those of cocaine and amphetamines; the primary psychological effects have a duration of 3 to 4 hours, with aftereffects such as tachycardia and mild stimulation lasting from 6 to 8 hours. High doses have been observed to cause intense, prolonged panic attacks in stimulant-intolerant users, there are anecdotal reports of psychosis from sleep withdrawal and addiction at higher doses or more frequent dosing intervals.

It has been noted to induce irresistible cravings to re-administer. Reported modalities of intake include oral consumption, smoking and intravenous use, it is active at 3–5 mg, with typical doses ranging between 5–20 mg. When assayed in mice, repeated exposure to MDPV causes not only an anxiogenic effect but increased aggressive behaviour, a feature, observed in humans; as with MDMA, MDPV caused a faster adaptation to repeated social isolation. A cross-sensitization between MDPV and cocaine has been evidenced. Furthermore, both psychostimulants, MDPV and cocaine, restore drug-seeking behavior with respect to each other, although relapse into drug-taking is always more pronounced with the conditioning drug. Moreover, memories associated with MDPV require more time to be extinguished. In MDPV-treated mice, a priming-dose of cocaine triggers significant neuroplasticity, implying a high vulnerability to its abuse; the long-term effects of MDPV on humans have not been studied, but it has been reported that mice treated with MDPV during adolescence show reinforcing behavior patterns to cocaine that are higher than the control group's.

These behavioural changes are related to alterations of factor expression directly related to addiction. All this suggests an increased vulnerability to cocaine abuse. MDPV undergoes CYP450 2D6, 2C19, 1A2, COMT phase 1 metabolism into methylcatechol and pyrrolidine, which in turn are glucuronated allowing it to be excreted by the kidneys, with only a small fraction of the metabolites being excreted into the stools. No free pyrrolidine will be detected in the urine. Molecularly, this is seen as demethylenation of methylenedioxypyrovalerone, followed by methylation of the aromatic ring via catechol-O-methyl transferase. Hydroxylation of both the aromatic ring and side chain takes place, followed by an oxidation of the pyrrolidine ring to the corresponding lactam, with subsequent detachment and ring opening to the corresponding carboxylic acid. MDPV may be quantified in blood, plasma or urine by gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry to confirm a diagnosis of poisoning in hospitalized patients or to provide evidence in a medicolegal death investigation.

Blood or plasma MDPV concentrations are expected to be in a range of 10–50 μg/L in persons using the drug recreationally, >50 μg/L in intoxicated patients, >300 μg/L in victims of acute overdose. In the UK, following the ACMD's report on substituted cathinone derivatives, MDPV is a Class B drug under The Misuse of Drugs Act 1971 Order 2010, making it illegal to sell, buy, or possess without a license. MDPV is listed as a controlled substance in Finland and Sweden. In Sweden a 33-year-old man has been sentenced to six years in prison by an appellate court, Hovrätt, for possession of 250 grams of MDPV, acquired prior to criminalization. In Western Australia, MDPV has been banned under the Poisons Act 1964, having been included in Appendix A Schedule 9 of the Poisons Act 1964 as from February 11, 2012; the Director of Public Prosecutions f

Toyosu Station

Toyosu Station is a railway station in Kōtō, Japan, operated by Tokyo Metro and Yurikamome. Toyosu Station is served by the Yurikamome; the station consists of an underground metro station on the Tokyo Metro Yurakucho Line, an elevated station forming the eastern terminus of the Yurikamome Line. The subway station has two island platforms located on the third basement level, serving four tracks; the two centre tracks were completed on 1 March 2013, for use by terminating services from the start of the revised timetable on 16 March 2013. Following the timetable revision on 15 October 2019 however, tracks 2 and 3 were shut down and subsequently covered up as a measure to alleviate congestion during the upcoming 2020 Tokyo Olympics; the station consists of a single elevated island platform serving two terminating tracks. The subway station opened on 8 June 1988 when the Yurakucho Line was extended from Shintomichō to Shin-kiba; the Yurikamome station opened on 27 March 2006. The Tokyo Metro station platforms were renumbered 1 to 4 from 1 March 2013 following completion of the two centre tracks for use by terminating trains.

In fiscal 2012, the Tokyo Metro station was used by an average of 160,196 passengers daily. The passenger figures for previous years are as shown below. Toyosu has gained popularity due to the increase in high-rise apartments, such as Park City Toyosu, The Toyosu Tower, City Towers Toyosu, the large shopping mall known as Lalaport Toyosu. Other places of note in the vicinity include the following. Gas Science Museum Shibaura Institute of Technology Showa University Toyosu Hospital Toyosu Library Fukagawa No. 5 Junior High School Toyosu Elementary School Toyosu-kita Elementary School List of railway stations in Japan Toyosu Station information Toyosu Station information