DISCRIMINATIVE STIMULUS PROPERTIES OF (-)EPHEDRINE

Ephedrine, a structural analog of methamphetamine, is one of the major constituents of legally available herbal dietary supplements. Althoug h racemic ephedrine and ephedra extract have been previously used as t raining drugs in drug discrimination studies, there is evidence that t he two optical isomers of ephedrine do not produce identical amphetami ne-like stimulus effects in rats. Consequently, we trained a group of six male Sprague-Dawley rats to discriminate 4 mg/kg of the more poten t 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 (ED, = 0.4 mg/kg), cocaine (ED,-, = 2.7 mg/kg), methylphenidate (ED50 = 1.2 mg/kg), S(-)methcathinone (ED 50 = 0.3 mg/kg), and caffeine (ED50 = 36.7 mg/kg), but stimulus genera lization failed to occur to either S(+)methamphetamine or methyl-1-(3, 4-methylenedioxyphenyl)-2-aminopropane (MDMA). In addition, although w e 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 les s potent than (+)amphetamine in (+)amphetamine-trained rats, whereas i t is only half as potent as (+)amphetamine in (-)ephedrine-trained ani mals; (b) that the (-)ephedrine stimulus failed to generalize to (+)me thamphetamine; and (c) that the (-)ephedrine stimulus generalized to ( +)ephedrine, it is concluded that the stimulus effects of (+)amphetami ne and (-)ephedrine as training drugs, while similar, are not identica l. It is also concluded that the stimulus effects of (-)ephedrine and those of the designer drug MDMA, while perhaps sharing some amphetamin ergic commonality, are nonidentical. (C) 1998 Elsevier Science Inc.