Methylenedioxypyrovalerone
Methylenedioxypyrovalerone (MDPV) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). 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 virtually inactive at the serotonin transporter. MDPV remained an obscure stimulant until around 2004 when it was reportedly sold as a designer drug. In the US, products containing MDPV and labeled as bath salts were sold as recreational drugs in gas stations, similar to the marketing for Spice and K2 as incense, until it was banned in 2011. Appearance The hydrochloride salt exists as a very fine crystalline powder; it is hygroscopic and thus tends to form clumps, resembling something like powdered sugar. Its color can range from pure white to a yellowish-tan and has a slight odor that strengthens as it colors. Impurities are likely to consist of either pyrrolidine or alpha-dibrominated alkylphenones—respectively, from either excess pyrrolidine or incomplete amination during synthesis. These impurities likely account for its discoloration and fishy (pyrrolidine) or bromine-like odor, which worsens upon exposure to air, moisture, or bases. Pharmacology 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 already 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, which has been 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 (α-PPP), 4'-methyl-α-pyrrolidinopropiophenone (M-α-PPP), 3',4'-methylenedioxy-α-pyrrolidinopropiophenone (MDPPP) and 1-phenyl-2-(1-pyrrolidinyl)-1-pentanone (α-PVP). Effects MDPV acts as a stimulant and has been reported to produce effects similar to those of cocaine, methylphenidate, and amphetamines. The primary psychological effects have a duration of roughly 3 to 4 hours, with aftereffects such as tachycardia, hypertension, and mild stimulation lasting from 6 to 8 hours. High doses have been observed to cause intense, prolonged panic attacks in stimulant-intolerant users, and there are anecdotal reports of psychosis from sleep withdrawal and addiction at higher doses or more frequent dosing intervals. It has also been repeatedly noted to induce irresistible cravings to re-administer. Reported modalities of intake include oral consumption, insufflation, smoking, rectal and intravenous use. It is supposedly 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 also increased aggressive behaviour, a feature that has already been observed in humans. As with MDMA, MDPV also 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