N-Ethylhexedrone

n-ethylhexedrone (also known as neh and hexen) is a lesser-known novel stimulant substance of the cathinone class. n-ethylhexedrone is a derivative of hexedrone and is part of a diverse group of compounds called the substituted cathinones. little is known about its pharmacology, although it likely acts by increasing levels of norepinephrine and dopamine in the brain.

the original synthesis date of n-ethylhexedrone is unknown. it appears to have emerged on the online research chemical market in late 2015. it is an example of a novel psychoactive substance specifically chosen to mimic the features of prohibited substances and bypass drug laws. it is one of a number of substances collectively referred to in popular culture as “bath salts”.

user reports characterize n-ethylhexedrone as having euphoric stimulant effects comparable to those of crack-cocaine and α-pvp-type compounds, particularly when they insufflated or vaporized. like other substituted cathinones, n-ethylhexedrone has gained notoriety for its association with compulsive redosing and addictive behaviors when abused.

very little is known about the pharmacology, metabolism, and toxicity of n-ethylhexedrone. due to this, it is highly advised to use harm reduction practices if using this substance.

history and culture

n-ethylhexedrone was first identified in a sample from the belgian customs laboratory which was received at the jrc on november 2015. in january 2016, it was identified at the jrc in a sample provided by french customs. subsequently, in february 2016, the emcdda received notifications of the identification of this substance from other countries, such as sweden, the netherlands, france, belgium and slovenia.

chemistry

n-ethylhexedrone is a molecule of the cathinone chemical class. the term “substituted cathinone” refers to a broad array of substances based on cathinone, the principally active constituent of the khat plant. cathinone is principally constituted of a amphetamine core (a phenethylamine core with an alkyl group attached to the alpha carbon) and an oxygen group attached to the beta carbon. cathinones are also known as the beta-ketone (βk) (double-bonded oxygen to the β-carbon) analogs of amphetamines.

notably, the cathinone backbone can be modified in three different places to create hundreds of possible compounds, which include substituents such as
on the aromatic ring, the alpha carbon, or the amine group.

pharmacology

very little data exists on the human pharmacokinetics and pharmacodynamics of n-ethylhexedrone and other substituted cathinones. like amphetamines, synthetic cathinones exert their stimulating and sympathomimetic effects via increasing synaptic concentration of catecholamines such as dopamine, serotonin and norepinephrine. these molecules are able to inhibit monoamine reuptake transporters producing a decreased clearance of the neurotransmitters from the synapse. furthermore, they may cause release of biogenic amines from intracellular stores.

synthetic cathinones are generally less able than amphetamines to cross the blood–brain barrier because the beta-keto group causes an increase in polarity. unlike other synthetic cathinones, pyrrolidine derivatives have a higher ability to cross the blood–brain barrier because the pyrrolidine ring confers a low polarity to these molecules. the studies on the metabolism of synthetic cathinones have shown that they are n-demethylated, the keto group is reduced to hydroxyl and ring alkyl groups are oxidised.