N-ethylnorpentylone

IUPAC Name

methyl (2S)-2-[[1-[(4-fluorophenyl)methyl]indazole-3-carbonyl]amino]-3-methylbutanoate

Year(s) and type of review / ECDD meetings
Drug Class

Recommendation (from TRS)

Substance identification
N-ethylnorpentylone (1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1- one) is a ring-substituted synthetic cathinone analogue that originally emerged in the 1960s during pharmaceutical drug development efforts. It is also known as ephylone and N-ethylpentylone. In its pure form, N-ethylnorpentylone exists as a racemic mixture in the form of a powder or crystalline solid. However, the substance is usually available as a capsule, powered tablet, pill or powder often sold as "Ecstasy" or MDMA. N-ethylnorpentylone is also available in its own right and is advertised for sale by Internet retailers.

WHO review history
N-ethylnorpentylone has not been previously pre-reviewed or critically reviewed by the WHO ECDD. A critical review was proposed based on information brought to WHO’s attention that N-ethylnorpentylone poses a serious risk to public health and has no recognized therapeutic use.

Similarity to known substances and effects on the central nervous system
The information currently available suggests that N-ethylnorpentylone is a psychomotor stimulant, as users exhibit effects including sweating, agitation, paranoia, tachycardia and cardiac arrest, which are consistent with other cathinones and psychomotor stimulant drugs. Not all reported adverse effects could be causally linked to N-ethylnorpentylone alone.

Its molecular mechanism of action is similar to the synthetic cathinones MDPV and α-PVP which are both listed in Schedule II of the Convention on Psychotropic Substances of 1971. In vitro investigations showed that N-ethylnorpentylone inhibited the reuptake of dopamine, noradrenaline and, to a lesser extent, serotonin, which is consistent with other closely related cathinones with known abuse liability.

There is no specific information available to indicate that N-ethylnorpentylone may be converted into a substance currently controlled under the UN conventions.

Dependence potential
No controlled experimental studies examining the dependence potential of N-ethylnorpentylone in humans or animals were available. However, based on its action in the central nervous system, it would be expected that N-ethylnorpentylone would have the capacity to produce a state of dependence similar to that of other stimulants such as the ones listed in Schedule II of the Convention on Psychotropic Drugs of 1971.

Actual abuse and/or evidence of likelihood of abuse
In rodent drug discrimination studies, N-ethylnorpentylone fully substituted for methamphetamine and cocaine, and it was also shown to increase activity levels, suggesting it has potential for abuse similar to other psychomotor stimulants.

N-Ethylnorpentylone has been detected in biological fluids collected from a number of cases of fatal and non-fatal intoxication. It is frequently used in combination with other drugs.

A number of countries in various regions have reported use or detection of this compound in seized materials or biological samples, including cases of driving under the influence of drugs. Increased seizures of N-ethylnorpentylone have been reported by the United States over the past 2 years. Between 2016 and 2018, a total of 125 toxicological reports associated with N-ethylnorpentylone were documented.

Therapeutic usefulness
N-Ethylnorpentylone is not known to have any therapeutic use.

Recommendation
N-Ethylnorpentylone is a synthetic cathinone with effects that are similar to other synthetic cathinones listed as Schedule II substances in the Convention on Psychotropic Substances of 1971. Its mode of action and effects are consistent with those of other cathinones, indicating that it has the potential for dependence and the likelihood of abuse. There is evidence of use of N-ethylnorpentylone in a number of countries in various regions, which has resulted in fatal and non-fatal intoxication. The substance causes substantial harm and has no therapeutic use.

■■ Recommendation: The Committee recommended that N-ethylnor- pentylone (1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1- one) be added to Schedule II of the 1971 Convention on Psychotropic Substances.

ECDD Recommendation

Inclusion in Schedule II of the 1971 Convention on Psychotropic Substances