Discriminative stimulus properties of (-)ephedrine.

Ephedrine, a structural analog of methamphetamine, is one of the major constituents of legally available herbal dietary supplements. Although racemic ephedrine and ephedra extract have been previously used as training drugs in drug discrimination studies, there is evidence that the two optical isomers of ephedrine do not produce identical amphetamine-like stimulus effects in rats. Consequently, we trained a group of six male Sprague-Dawley rats to discriminate 4 mg/kg of the more potent optical isomer of ephedrine, (-)ephedrine, from saline vehicle. The (-)ephedrine stimulus (ED50 = 0.8 mg/kg) generalized to other central stimulants such as S(+)amphetamine (ED50 = 0.4 mg/kg), cocaine (ED50 = 2.7 mg/kg), methylphenidate (ED50 = 1.2 mg/kg), S(-)methcathinone (ED50 = 0.3 mg/kg), and caffeine (ED50 = 36.7 mg/kg), but stimulus generalization failed to occur to either S(+)methamphetamine or N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA). In addition, although we have previously shown that a (+)amphetamine stimulus generalizes to (-)ephedrine but not to (+)ephedrine, in the present investigation the (-)ephedrine stimulus generalized to (+)ephedrine (ED50 = 2.6 mg/kg). From the findings (a) that (-)ephedrine is approximately 10 times less potent than (+)amphetamine in (+)amphetamine-trained rats, whereas it is only half as potent as (+)amphetamine in (-)ephedrine-trained animals; (b) that the (-)ephedrine stimulus failed to generalize to (+)methamphetamine; and (c) that the (-)ephedrine stimulus generalized to (+)ephedrine, it is concluded that the stimulus effects of (+)amphetamine and (-)ephedrine as training drugs, while similar, are not identical. It is also concluded that the stimulus effects of (-)ephedrine and those of the designer drug MDMA, while perhaps sharing some amphetaminergic commonality, are nonidentical.