U-47700

Substance identification
Chemically, U-47700 is 3,4-dichloro-N-(2-dimethylamino-cyclohexyl)-N- methyl-benzamide. U-47700 has two chiral centres resulting in four isomers; cis- and trans-conformations, each of which has two enantiomers (cis, 1R,2R, and 1S,2S; trans, 1R,2S and 1S,2R).

Previous review
U-47700 has not previously been pre-reviewed or critically reviewed by the Committee. A direct critical review was proposed based on information brought to the attention of WHO that U 47700 is clandestinely manufactured, poses a risk to public health and society, and has no recognized therapeutic use by any Party.

Similarity to known substances and effects on the central nervous system
The closest controlled substance that is structurally related to U-47700 is AH- 7921, and they are structural isomers of one another. AH-7921 is controlled as a Schedule I drug under the Single Convention on Narcotic Drugs, 1961, as amended by the 1972 Protocol, in 2015. U-47700 binds and has functional activity at the mu opioid receptor and at the delta opioid receptor. It has antinociceptive activity in mice, with about 7.5 times the potency of morphine. Similar to morphine, case reports indicate that it produces pinpoint pupils, respiratory depression, cyanosis and depressed consciousness that is clinically reversible with naloxone. Confirmed fatalities (>15) associated with the use of U-47700 have occurred in Europe and in the United States.

Dependence potential
No controlled laboratory studies in animals or humans have been reported regarding the dependence effects of U-47700. Users, however, report the induction of tolerance and the emergence of withdrawal signs and symptoms upon discontinuing use of U-47700, suggestive of physical dependence.

Actual abuse and/or evidence of likelihood of abuse
No controlled laboratory studies in animals or humans have been reported regarding the abuse potential of U-47700. U-47700, however, is aggressively marketed on the Internet, often as a heroin or an oxycodone substitute, as itself, or in combination with other drugs. There have also been many seizures in Europe and in North America, some single seizures involving hundreds of pills. Users report administering U-47700 via the oral, insufflation, intravenous and rectal routes, and via an inhaler using a liquid solution. Some countries have placed U-47700 under national control, and recently (14 November 2016) the United States placed U-47700 under its Controlled Substances Act stating that this was necessary to avoid an imminent hazard to public safety.

Therapeutic usefulness
Although investigated preclinically as an analgesic, U-47700 has no history as a marketed medical product, nor are there any known current marketing authorizations for it as a medicinal product.

Recommendation
U-47700 (3,4-dichloro-N-(2-dimethylamino-cyclohexyl)-N-methyl-benzamide) is a compound liable to similar abuse and with similar ill effects to controlled opioids such as morphine and AH-7921 that are included in Schedule I of the Single Convention on Narcotic Drugs of 1961. It has no recorded therapeutic use, and its use has resulted in fatalities. There is sufficient evidence that it is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control. Thus, because it meets the required condition of similarity, it is recommended that U-47700 be placed in Schedule I of the Single Convention on Narcotic Drugs, 1961, as consistent with Article 3, paragraph 3 (iii) of that Convention in that the substance is liable to similar abuse and productive of similar ill effects to drugs in Schedule I.