Locomotor and discriminative stimulus effects of N-cyclohexyl butylone and N-cyclohexyl methylone.
Michael B. Gatch, Shuping Jia, Ritu A. Shetty, Rebecca D. Hill, Nathalie Sumien, Michael J Forster
Frontiers in Pharmacology 2026 DOI: 10.3389/fphar.2026.1823177 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Male Swiss-Webster mice and male Sprague-Dawley rats |
| Interventions | N-cyclohexyl butylone N-cyclohexyl methylone methamphetamine cocaine MDMA |
| Topics | MDMA |
| Keywords | Cathinones Cocaine Drug discrimination Methamphetamine Psychostimulants Rodents |
| Key findings | N-cyclohexyl butylone fully substituted for methamphetamine and cocaine in drug discrimination tests, whereas N-cyclohexyl methylone failed to fully substitute and caused convulsions. |
Abstract
N-Cyclohexyl butylone and N-cyclohexyl methylone are cathinones found on the street that produce morbidity and mortality, but are not yet legally controlled, and there has been little or no pharmacological testing of these compounds. Both compounds have a large moiety on the N-position that may alter their pharmacological effects. Locomotor stimulant effects of N-cyclohexyl butylone and N-cyclohexyl methylone were tested in male Swiss-Webster mice. N-Cyclohexyl butylone and N-cyclohexyl methylone were tested in male Sprague-Dawley rats trained to discriminate methamphetamine (1 mg/kg), cocaine (10 mg/kg) or 3,4-methylenedioxymethamphetamine (MDMA, 1.5 mg/kg) from saline. Both N-cyclohexyl butylone (ED50 = 2.80 mg/kg) and N-cyclohexyl methylone (ED50 = 33.46 mg/kg) produced dose- and time-dependent stimulation of locomotor activity that was both less potent and less efficacious than that of methamphetamine (ED50 = 0.35 mg/kg). N-Cyclohexyl butylone fully substituted for the discriminative stimulus effects of methamphetamine (ED50 = 9.85 mg/kg) and cocaine (ED50 = 14.54 mg/kg). N-Cyclohexyl methylone failed to fully substitute for cocaine or methamphetamine up to doses that produced convulsions. Both compounds failed to substitute for MDMA up to doses that suppressed responding. N-cyclohexyl butylone may produce psychostimulant-like effects adequate to motivate illicit use, whereas the weak psychostimulant-like effects of N-cyclohexyl methylone may suggest a reduced liability for illicit use, but the compound may be more dangerous due to its convulsant effects. The N-cyclohexyl moiety may have contributed to the reduced efficacy of N-cyclohexyl methylone, while the longer alpha-side chain of N-cyclohexyl butylone may have countered the effect of the large N-position moiety.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 10
- The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain. European Journal of Pharmacology March 22, 2007
- Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation ACS Chemical Neuroscience March 9, 2021
- Pharmacological effects of methylone and MDMA in humans Frontiers in Pharmacology February 17, 2023
- N-methyl-1-(1,3-benzodioxol-5-yl)-2-butanamine (MBDB): its properties and possible risks. Addiction Biology July 1, 2000
- Discriminative-Stimulus Effects of Synthetic Cathinones in Squirrel Monkeys The International Journal of Neuropsychopharmacology April 26, 2021
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