IUPAC Name
1-cyclohexyl-4-(1,2-diphenylethyl)piperazine
Current Scheduling Status
Year(s) and type of review / ECDD meetings
Drug Class
Recommendation (from TRS)
Substance identification
Chemically, MT-45 is 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine. MT-45 has two enantiomers and is commonly available as the racemic mixture.
Previous review
MT-45 has not been previously reviewed by the Committee. A critical review was proposed based on information brought to WHO’s attention that MT-45 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
Structurally, MT-45 is somewhat similar to lefetamine (SPA; (R)-N,N-dimethyl- 1,2-diphenylethylamine), a stimulant with analgesic effects, that is controlled as a Schedule IV drug under the UN 1971 Convention on Psychotropic Substances, but conversion into SPA is considered difficult.
MT-45 (the racemate) binds to the µ-, δ-, and κ-opioid receptors and has many of the effects of a classical opioid such as morphine. It inhibits electrically induced contractions of the guinea-pig ileum, it has antinociceptive effects in thermal, mechanical, electrical and chemical pain models. It reduces gastrointestinal transit time, depresses respiration, produces Straub tail in mice and induces hyperglycaemia. The isomers show subtle differences. The S(+)- isomer produces most of the morphine-like effects whereas the R(−)-isomer has been reported not to depress respiration, produce Straub tail, or to have hyperglycaemic effects, and it has a 1000-fold higher affinity for both the σ1 and σ2 receptors than for the opioid receptors.
Dependence potential
Regarding MT-45’s ability to induce physical dependence, the mixed opioid agonist-antagonist, nalorphine, is able to precipitate opioid-like withdrawal jumping in MT-45-treated mice, suggestive of physical dependence. MT-45 is also able to attenuate signs of morphine withdrawal in mice thus demonstrating cross-dependency with morphine. Controlled studies examining the potential physical dependence effects of MT-45 in human subjects have not been reported; however, user websites contain reports of withdrawal-like symptoms following use of MT-45.
Actual abuse and/or evidence of likelihood of abuse
MT-45 is being abused for non-medical reasons in several countries, most often apparently for its opioid-like effects. Recognizing the abuse of this drug and its associated toxicity, several European countries have brought MT-45 under some level of regulatory control. Additionally, the Synthetic Drug Control Act of 2015 is currently circulating the United States legislature, and that is also proposing to place MT-45 in the most restrictive schedule under the United States system. Scholarly reports documenting the prevalence and incidence of abuse of MT-45 are not available and neither are any primary preclinical studies pertinent to the prediction of the likelihood of abuse of MT-45 other than to physical dependence. Fatal and non-fatal intoxications involving MT-45 have been reported.
Therapeutic usefulness
There are no known approved human therapeutic applications for MT-45.
Recommendation
MT-45 is a compound with morphine-like effects. The Committee considered that the degree of risk to public health and society associated with the abuse liability and accompanying evidence warranted its placement under international control. Therapeutic use in humans has not been recorded. The Committee recommended that MT-45 be placed in Schedule I of the 1961 Single Convention, as amended by the 1972 Protocol.
Chemically, MT-45 is 1-cyclohexyl-4-(1,2-diphenylethyl)piperazine. MT-45 has two enantiomers and is commonly available as the racemic mixture.
Previous review
MT-45 has not been previously reviewed by the Committee. A critical review was proposed based on information brought to WHO’s attention that MT-45 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
Structurally, MT-45 is somewhat similar to lefetamine (SPA; (R)-N,N-dimethyl- 1,2-diphenylethylamine), a stimulant with analgesic effects, that is controlled as a Schedule IV drug under the UN 1971 Convention on Psychotropic Substances, but conversion into SPA is considered difficult.
MT-45 (the racemate) binds to the µ-, δ-, and κ-opioid receptors and has many of the effects of a classical opioid such as morphine. It inhibits electrically induced contractions of the guinea-pig ileum, it has antinociceptive effects in thermal, mechanical, electrical and chemical pain models. It reduces gastrointestinal transit time, depresses respiration, produces Straub tail in mice and induces hyperglycaemia. The isomers show subtle differences. The S(+)- isomer produces most of the morphine-like effects whereas the R(−)-isomer has been reported not to depress respiration, produce Straub tail, or to have hyperglycaemic effects, and it has a 1000-fold higher affinity for both the σ1 and σ2 receptors than for the opioid receptors.
Dependence potential
Regarding MT-45’s ability to induce physical dependence, the mixed opioid agonist-antagonist, nalorphine, is able to precipitate opioid-like withdrawal jumping in MT-45-treated mice, suggestive of physical dependence. MT-45 is also able to attenuate signs of morphine withdrawal in mice thus demonstrating cross-dependency with morphine. Controlled studies examining the potential physical dependence effects of MT-45 in human subjects have not been reported; however, user websites contain reports of withdrawal-like symptoms following use of MT-45.
Actual abuse and/or evidence of likelihood of abuse
MT-45 is being abused for non-medical reasons in several countries, most often apparently for its opioid-like effects. Recognizing the abuse of this drug and its associated toxicity, several European countries have brought MT-45 under some level of regulatory control. Additionally, the Synthetic Drug Control Act of 2015 is currently circulating the United States legislature, and that is also proposing to place MT-45 in the most restrictive schedule under the United States system. Scholarly reports documenting the prevalence and incidence of abuse of MT-45 are not available and neither are any primary preclinical studies pertinent to the prediction of the likelihood of abuse of MT-45 other than to physical dependence. Fatal and non-fatal intoxications involving MT-45 have been reported.
Therapeutic usefulness
There are no known approved human therapeutic applications for MT-45.
Recommendation
MT-45 is a compound with morphine-like effects. The Committee considered that the degree of risk to public health and society associated with the abuse liability and accompanying evidence warranted its placement under international control. Therapeutic use in humans has not been recorded. The Committee recommended that MT-45 be placed in Schedule I of the 1961 Single Convention, as amended by the 1972 Protocol.
ECDD Recommendation
Inclusion in Schedule I of the 1961 Convention on Narcotic Drugs
Link to full TRS
who_trs_998_eng.pdf330.66 KB
MS Questionnaire Report