Cardiovascular Differences Between Phenylpropanolamine and Its Related Norephedrine Isomers in the Rat

Various studies have confused the norephedrine and norpseudoephedrine isomers with phenylpropanolamine (PPA,  d,l -norephedrine). This confusion has led us to investigate the pharmacological activity of the norephedrine (NOR) and norpseudoephedrine (NORP) isomers in the cardiovascular system of the urethane:chloralose anesthetized rat. Following intravenous administration, in a cumulative-dose fashion,  I -NOR and PPA were the most potent compounds at increasing arterial blood pressure, while  d -NOR,  d -NORP, and  I -NORP were relatively inactive at the doses tested (0.31–10 mg/kg). Prior reserpinization did not significantly shift the cumulative dose-response curves for  I -NOR and PPA. Repetitive injections of PPA and  I -NOR (1 mg/kg, 4 doses at 5-min intervals) failed to produce tachyphylaxis to the pressor response. On the other hand, when  d -NORP was administered in a similar fashion, tachyphylaxis to the second and subsequent doses was observed. These studies demonstrate that significant mechanistic differences exist between these norephedrine isomers.