Naphyrone, also known as O-2482 and naphthylpyrovalerone, is a

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

of the

cathinone Cathinone (; also known as β-ketoamphetamine) is a monoamine alkaloid found in the shrub ''Catha edulis'' (khat) and is chemically similar to ephedrine, cathine, methcathinone and other amphetamines. It is probably the main contributor to t ...

and naphthylaminopropane families. It was derived from

pyrovalerone (Centroton, 4-Methyl-β-keto-prolintane, Thymergix, O-2371) is a central nervous system (CNS) stimulant that acts as a norepinephrine–dopamine reuptake inhibitor (NDRI). It was developed in the 1980s and had briefly been approved in Spain an ...

and acts as a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI). Naphyrone has been reported as a novel

designer drug 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. ...

. No safety or toxicity data is available on the drug. The drug has been marketed under the name “NRG-1,” although only a minority of samples of substances sold under this name have been found to actually contain naphyrone, and even samples that proved to contain genuine β-naphyrone were in some cases also found to contain the 1-naphthyl isomer α-naphyrone in varying proportions, further confusing the reported effects profile.

Use in the United Kingdom

Naphyrone emerged as a new legal high in the United Kingdom only months after the ban of similar drug

mephedrone Mephedrone, also known as , , and , is a synthetic stimulant drug belonging to the amphetamine and cathinone classes. It is commonly referred to by slang names such as drone, , white magic, meow meow, and bubble. Chemically, it is similar to ...

(which was also a

derivative). Until July 2010 the substance was not controlled by the

Misuse of Drugs Act 1971 The Misuse of Drugs Act 1971 (c. 38) is an act of the Parliament of the United Kingdom. It represents action in line with treaty commitments under the Single Convention on Narcotic Drugs, the Convention on Psychotropic Substances, and the ...

and was therefore not illegal for someone to possess. The Medicines Act prevented naphyrone from being sold for human consumption, and therefore it was sometimes sold as 'pond cleaner' or as another substance not normally consumed by humans. A study by researchers at Liverpool John Moores University found that only one out of ten products labelled as "NRG-1" actually contained naphyrone when they were subjected to laboratory analysis. Compounds found in products labelled NRG-1 included MDPV, flephedrone,

butylone Butylone, also known as β-keto-''N''-methylbenzodioxolylbutanamine (βk-MBDB), is a psychoactive drug of the substituted phenethylamine, phenethylamine, substituted amphetamine, amphetamine, phenylisobutylamine, and substituted cathinone, cathin ...

and

caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...

, one product tested was

inorganic An inorganic compound is typically a chemical compound that lacks carbon–hydrogen bonds⁠that is, a compound that is not an organic compound. The study of inorganic compounds is a subfield of chemistry known as '' inorganic chemistry''. Inor ...

in composition. In the case of an individual possessing a product labelled NRG-1 that contains MDPV or other illegal substances, they are in possession of a controlled substance. On 12 July 2010, the

Home Office The Home Office (HO), also known (especially in official papers and when referred to in Parliament) as the Home Department, is the United Kingdom's interior ministry. It is responsible for public safety and policing, border security, immigr ...

announced that naphyrone had been banned and made a Class B drug, following a report from the

Advisory Council on the Misuse of Drugs The Advisory Council on the Misuse of Drugs (ACMD) is a British statutory advisory non-departmental public body, which was established under the Misuse of Drugs Act 1971. Mandate Its terms of reference, according to the Act, are as follows: ...

Pharmacology

As a triple reuptake inhibitor, naphyrone has been shown ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'' to affect the

reuptake Reuptake is the reabsorption of a neurotransmitter by a neurotransmitter transporter located along the plasma membrane of an axon terminal (i.e., the pre-synaptic neuron at a synapse) or glial cell after it has performed its function of transmi ...

of the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

by interacting with the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

(SERT),

dopamine transporter The dopamine transporter (DAT, also sodium-dependent dopamine transporter) is a membrane-spanning protein coded for in humans by the ''SLC6A3'' gene (also known as ''DAT1''), that pumps the neurotransmitter dopamine out of the synaptic cleft ba ...

(DAT), and

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium ...

(NET). One study found that the

dissociation constant In chemistry, biochemistry, and pharmacology, a dissociation constant (''K''D) is a specific type of equilibrium constant that measures the propensity of a larger object to separate (dissociate) reversibly into smaller components, as when a complex ...

of naphyrone interacting with SERT is 33.1 nM ± 1.1, with DAT is 20.1 nM ± 7.1 and with NET is 136 nM ± 27. The concentration of naphyrone required to inhibit the transporters by 50% is 46.0 nM ± 5.5 for SERT, 40.0 nM ± 13 for DAT and 11.7 nM ± 0.9 for NET. Of a number of

analogues tested, naphyrone was found to be the only serotonin–norepinephrine–dopamine reuptake inhibitor found to be active at n M concentrations. Some samples of β-naphyrone sold have also been found to contain the alternative

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

α-naphyrone, presumably produced accidentally as an impurity in synthesis. The ''in vitro'' data available in the scientific literature was all obtained using pure β-naphyrone, and the pharmacological properties of α-naphyrone are unknown, further complicating the pharmacological profile of this little-studied designer drug.

References

{{Phenethylamines Alpha-Propylphenethylamines Cathinones Designer drugs 2-Naphthyl compounds Naphthylethylamines Propyl compounds Pyrrolidinophenones Serotonin–norepinephrine–dopamine reuptake inhibitors Stimulants

Use in the United Kingdom

Pharmacology

See also

References