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MT-45 [1-cyclohexyl-4-(1,2-diphenylethyl)piperazine], also known as IC-6, NSC 299236 and CDEP, is a synthetic opioid developed as a therapeutic drug candidate in the 1970s by the Dainippon Pharmaceutical Co. in Japan. MT-45 has never been commercially available as a therapeutic agent; however, it has appeared on the illicit recreational drug market in recent years, but not extensively.

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MT-45 is structurally distinct from other therapeutic opioids (Fig. 1a) and has structural similarities to the dissociative drug diphenidine (Fig. 1f) which is an N-methyl-D-aspartic acid (NMDA) receptor agonist. MT-45 is a selective μ-opioid receptor (MOR-1) agonist showing nM binding affinities to MOR-1, but is less potent than morphine, with considerably lower δ– and κ-opioid receptor (DOR-1 and KOR-1) affinities [1].

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The racemic mixture has opioid-like properties in animal models with a potency similar to morphine, with the (S)-enantiomer being considerably more potent than the (R)-isomer. Antinociceptive (reduced sensitivity to pain) effects were studied in vivo using a radiant heat tail flick assay in mice, showing that MT-45 had analgesic properties similar to morphine [1], which were further confirmed by Montesano et al. [12].

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Users reporting their subjective experiences with the drug on online fora have often reported dissociative effects after consuming MT-45, and such effects may be mediated via the NMDA receptor; however, no formal studies on the NMDA receptor affinity of MT-45 or its metabolites have been reported.

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MT-45 was first detected on the illicit market in seized samples in Japan [16] and was first reported in Europe by the STRIDA project in Sweden in nine nonfatal intoxication cases [17]. Detection of MT-45 in biological fluids was reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in relation to 28 fatal and 12 nonfatal intoxications in Sweden, the substance being implicated in 19 of the fatalities either as the cause of death or as a contributing factor and was commonly detected with other psychoactive substances [18].

Other Names; 1-cyclohexyl-4-(1,2-diphenylethyl)-piperazine; Dihydrochloride; IC-6; NSC 299236; CDEP, MT-45, IC-6, Wow, IC 6, CAS 41537-67-1, MT 45, MT45