A designer drug is a structural or functional analog of a controlled substance that has been designed to mimic the pharmacological effects of the original drug, while avoiding classification as illegal and/or detection in standard drug tests. Designer drugs include psychoactive substances that have been designated by the European Union as new psychoactive substances (NPS) as well as analogs of performance-enhancing drugs such as designer steroids. Some of these were originally synthesized by academic or industrial researchers in an effort to discover more potent derivatives with fewer side effects and shorter duration and were later co-opted for recreational use. Other designer drugs were prepared for the first time in clandestine laboratories. Because the efficacy and safety of these substances have not been thoroughly evaluated in animal and human trials, the use of some of these drugs may result in unexpected side effects.
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.
α-Pyrrolidinopentiophenone is a synthetic stimulant of the cathinone class developed in the 1960s that has been sold as a designer drug. Colloquially, it is sometimes called flakka. α-PVP is chemically related to pyrovalerone and is the ketone analog of prolintane.
Substituted cathinones, which include some stimulants and entactogens, are derivatives of cathinone. They feature a phenethylamine core with an alkyl group attached to the alpha carbon, and a ketone group attached to the beta carbon, along with additional substitutions. Cathinone occurs naturally in the plant khat whose leaves are chewed as a recreational drug.
Pentedrone is a stimulant of the cathinone class that has been sold as a designer drug and has been found since 2010 as an ingredient in a number of "bath salt" mixes sold as legal highs.
Bath salts are a group of recreational designer drugs. The name derives from instances in which the drugs were disguised as bath salts. The white powder, granules, or crystals often resemble Epsom salts, but differ chemically. The drugs' packaging often states "not for human consumption" in an attempt to circumvent drug prohibition laws. Additionally, they may be mislabeled as plant food, powdered cleaner, and other such products.
N-Ethylbuphedrone is a stimulant of the cathinone class that has been sold as a designer drug. It is the β-ketone analogue of N,alpha-diethylphenylethylamine.
Diphenidine is a dissociative anesthetic that has been sold as a designer drug. The synthesis of diphenidine was first reported in 1924, and employed a Bruylants reaction analogous to the one that would later be used to discover phencyclidine in 1956. Shortly after the 2013 UK ban on arylcyclohexylamines, diphenidine and the related compound methoxphenidine became available on the grey market. Anecdotal reports describe high doses of diphenidine producing "bizarre somatosensory phenomena and transient anterograde amnesia." Diphenidine and related diarylethylamines have been studied in vitro as treatments for neurotoxic injury and are antagonists of the NMDA receptor. In dogs diphenidine exhibits greater antitussive potency than codeine phosphate.
α-Pyrrolidinohexiophenone is a synthetic stimulant drug of the cathinone class developed in the 1960s which has been reported as a novel designer drug.
4'-Methoxy-α-pyrrolidinopentiophenone is a stimulant drug of the cathinone class that has been sold online as a designer drug.
Mexedrone is a stimulant and an entactogen drug of the cathinone class that has been sold online as a designer drug. It is the alpha-methoxy derivative of Mephedrone.
The substituted benzofurans are a class of chemical compounds based on the heterocyclyc and polycyclic compound benzofuran. Many medicines use the benzofuran core as a scaffold, but most commonly the term is used to refer to the simpler compounds in this class which include numerous psychoactive drugs, including stimulants, psychedelics and empathogens. In general, these compounds have a benzofuran core to which a 2-aminoethyl group is attached, and combined with a range of other substituents. Some psychoactive derivatives from this family have been sold under the name Benzofury.
N-Ethylhexedrone (also known as α-ethylaminocaprophenone, N-ethylnorhexedrone, hexen, and NEH) is a stimulant of the cathinone class that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI) with IC50 values of 0.0978 and 0.0467 μM, respectively. N-Ethylhexedrone was first mentioned in a series of patents by Boehringer Ingelheim in the 1960s which led to the development of the better-known drug methylenedioxypyrovalerone (MDPV). Since the mid-2010s, N-ethylhexedrone has been sold online as a designer drug. In 2018, N-ethylhexedrone was the second most common drug of the cathinone class to be identified in Drug Enforcement Administration seizures.
MDPHP (3',4'-Methylenedioxy-α-pyrrolidinohexiophenone) is a stimulant of the cathinone class originally developed in the 1960s, which has been reported as a novel designer drug. In the UK its slang name is monkey dust. It is closely related to the potent stimulant MDPV though with slightly milder effects, and has been used as an alternative in some countries following the banning of MDPV.
α-PCyP is a stimulant drug of the cathinone class that has been sold online as a designer drug. In a series of alpha-substituted pyrrolidinyl cathinone derivatives developed in 2015, the alpha-cyclopentyl derivative was found to have around the same potency in vitro as an inhibitor of the dopamine transporter as the alpha-propyl derivative α-PVP, while the alpha-cyclohexyl derivative α-PCyP was around twice as strong.
N,N-Dimethylpentylone is a substituted cathinone derivative with stimulant effects, which has been sold as a designer drug, first detected in Sweden in 2014.
MFPVP (3-Methyl-4-fluoro-α-pyrrolidinovalerophenone) is a recreational designer drug from the substituted cathinone family, with stimulant effects. It was first identified in Sweden in April 2020 and was among the most widely encountered substituted cathinone derivatives in 2021, though it since appears to have declined in prevalence. It is illegal in Virginia.
3-Fluoro-N-ethylbuphedrone (3F-NEB) is a substituted cathinone derivative with stimulant effects which has been sold as a designer drug. It was first identified in Sweden in 2021.
2-Methyl-alpha-PVP (2-Me-PVP) is a substituted cathinone derivative with stimulant effects which has been sold as a designer drug. It was first identified in Sweden in 2021.
3-Fluoro-alpha-PHP (3F-PHP) is a substituted cathinone derivative with stimulant effects which has been sold as a designer drug. It was first identified in Sweden in 2020 and continues to be detected in seized drug samples, though it appears to have been less widely used than related compounds such as 3F-PVP and 3F-PiHP.
