P-Hydroxy-norephedrine as a possible mediator causing the reduction of oral intake of D-amphetamine in rats

Designer drugs: a medicinal chemistry perspective (II)

“…Improving brain penetration by fluorine substitution at an aromatic position of amphetamine and methamphetamine, to give the analogs B24–29 , was presumably intended to afford increased efficacy and rapid onset while maintaining the pharmacological effects of the parent amphetamines. Moreover, substitution at the 4‐position prevents P450 oxidase metabolism to afford the corresponding 4‐hydroxyamphetamine, which has been hypothesized to be aversive to the intake of stimulants, 49 thereby affecting the user's experience. Evaluation of 4‐fluoroamphetamine ( B26 ) in rodents has shown it to fully substitute for the discriminative effects of MDMA and amphetamine 50 consistent with a clinical study that has concluded that B26 induces a mild psychedelic state that lies between these caused by MDMA and amphetamine 51 .…”