An examination of isomeric phenylpropanolamines in (-)ephedrine-trained rats

A total of eight isomeric phenylpropanolamines are possible when the terminal amine is either an N-monomethylamine or a primary amine: (-)ephedrine, (+)ephedrine, (+)pseudoephedrine, (-)pseudoephedrine, (-)norephedrine, (+)norephedrine, (+)cathine, and (-)cathine. Few previous studies have examined the individual optical isomers of these phenylpropanolamines and, with the exception of one report on locomotor effects, no comparative behavioral data have been published on this series of agents. Using rats trained to discriminate 4 mg/kg of (-)ephedrine (i.p.) from saline vehicle using standard operant conditioning with a VI 15-s schedule of reinforcement, all eight agents were examined in tests of stimulus generalization. The (-)ephedrine stimulus (ED50 = 0.90 mg/kg) generalized to (+)ephedrine (ED50 = 2.64 mg/kg), (+)pseudoephedrine (ED50 = 6.58 mg/kg), (-)norephedrine (ED50 = 1.86 mg/kg), (+)norephedrine (ED50 = 5.75 mg/kg), and (+)cathine (ED50 = 4.87 mg/kg). The (-)ephedrine stimulus failed to generalize to either (-)pseudoephedrine or (-)cathine; the latter agents produced a maximum of 29 and 31% (-)ephedrine-appropriate responding, respectively. Thus, (a) six of the eight phenylpropanolamines produced ephedrine-like stimulus effects, (b) (-)ephedrine was the most potent of the examined agents, and (c) where stimulus generalization occurred, ED50 values spanned less than a tenfold range.