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 January 1, 2026 Peer reviewed DOI: 10.3389/fphar.2026.1823177 via PubMed
Summary
N-Cyclohexyl butylone and N-cyclohexyl methylone, two street cathinones, were tested for their effects on locomotor activity in male mice and rats. N-Cyclohexyl butylone showed significant stimulation of locomotor activity with an ED50 of 2.80 mg/kg, fully substituting for the effects of methamphetamine and cocaine. In contrast, N-cyclohexyl methylone was less effective, failing to fully substitute for these drugs even at higher doses that caused convulsions. These findings suggest differing potential for illicit use and safety concerns.
Study at a glance
| Design | experimental study |
|---|---|
| Population | male Swiss-Webster mice and male Sprague-Dawley rats |
| Key finding | N-Cyclohexyl butylone produced significant locomotor stimulation and fully substituted for methamphetamine and cocaine, while N-cyclohexyl methylone did not fully substitute for these drugs even at convulsant doses. |
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.