Locomotor and discriminative stimulus effects of N-cyclohexyl butylone and N-cyclohexyl methylone

Background 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. Methods 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. Results Both N-cyclohexyl butylone (ED 50 = 2.80 mg/kg) and N-cyclohexyl methylone (ED 50 = 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 (ED 50 = 0.35 mg/kg). N-Cyclohexyl butylone fully substituted for the discriminative stimulus effects of methamphetamine (ED 50 = 9.85 mg/kg) and cocaine (ED 50 = 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. Conclusion 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.