2-methyl-AP-237

Substance identification
2-Methyl-AP-237 (IUPAC chemical name: 1-[2-Methyl-4-(3-phenyl-2-propen- 1-yl)-1-piperazinyl]-1-butanone) is a methyl derivative of the opioid analgesic AP-237 (or bucinnazine).

2-Methyl-AP-237 has been described as a white crystalline powder, a crystalline solid and a white solid.

WHO review history
2-Methyl-AP-237 has not been formally reviewed by WHO and is not currently under international control. Information was brought to the attention of WHO that this substance is manufactured clandestinely, poses a risk to public health and has no recognized therapeutic use. 15

Similarity to known substances and effects on the central nervous system
2-Methyl-AP-237 is an opioid analgesic with a rapid onset of action and a potency and analgesic effects similar to those of fentanyl, which is listed under Schedule I of the Single Convention on Narcotic Drugs, 1961. In animals, it produces acute toxic effects typical of opioids, including respiratory depression. Limited research has been reported on the effects of 2-methyl-AP-237 in humans, although its respiratory depressant effects have been observed, which can be reversed by the opioid antagonist, naloxone.

Dependence potential
No controlled studies of the dependence potential of 2-methyl-AP-237 have been reported in animals or humans. As it is a µ-opioid receptor agonist, it would be expected to produce dependence similar to that induced by other opioids, such as morphine and fentanyl. Online self-reports described tolerance and withdrawal.

Actual abuse and/or evidence of likelihood of abuse
In an animal model predictive of abuse potential, 2-methyl-AP-237 was shown to produce opioid-like effects with a potency between those of morphine and fentanyl. These effects were blocked by the opioid antagonist, naltrexone.

No controlled studies on the abuse potential of 2-methyl-AP-237 in humans have been reported, but, as it is a µ-opioid receptor agonist, it would be expected to produce euphoria and other effects predictive of high abuse liability. Online self- reports support its euphoric and other opioid effects.

Seizures of 2-methyl-AP-237 have been reported in multiple countries in two regions.

A number of deaths in which 2-methyl-AP-237 has been found have been reported, often with multiple substances involved. The deaths occurred in a number of countries and regions.

Therapeutic usefulness
2-Methyl-AP-237 is not known to have any therapeutic use.

Recommendation
2-Methyl-AP-237 (IUPAC chemical name: 1-[2-Methyl-4-(3-phenyl-2-propen-1- yl)-1-piperazinyl]-1-butanone) is a synthetic opioid that is liable to abuse and to have ill effects similar to those of other opioids that are controlled under Schedule I of the 1961 Single Convention on Narcotic Drugs. Its use has been reported in a number of countries and has been associated with adverse effects, including death. It has no known therapeutic use and is likely to cause substantial harm.

Recommendation: The Committee recommended that 2-methyl-AP-237 (IUPAC chemical name: 1-[2-Methyl-4-(3-phenyl-2-propen-1-yl)-1-piperazinyl]-1- butanone) be added to Schedule I of the 1961 Single Convention on Narcotic Drugs.