A PHARMACOLOGiCAL STUDY OF THE EPHEDRINE ISOMERS

¹ College of Pharmacy, The Ohio State University, Columbus, Ohio

Pharmacological effects of the four ephedrine isomers were investigated. There was no essential difference between the i.v. LD50's of the isomers in mice. In anesthetized dogs the relative pressor potencies of D(-)-ephedrine, L(+)-ephedrine, L(+)-pseudoepherine were 100, 33, and 20, respectively. Effects on heart rate paralleled pressor effects. D(-)-Pseudoephedrine at doses of 0.33 and 3.3 mg/kg caused a slight rise in blood pressure followed by a transitory fall. At doses of 9.9 and 16.5 mg/kg it was depressor only. The depressor effect was present in the norepinephrine infused spinal cat, dogs pretreated with diphenhydramine, and dichloroisoproterenol. In anesthetized dogs pretreated with hexamethonium a pressor effect was observed. D(-)-Pseudoephedrine caused an increase in heart rate at all dose levels. In anesthetized cats similar effects were obtained. In spinal cats it produced a very slight pressor effect which was approximately [unknown] that of D(-)-ephedrrne.

In anesthetized dogs with doses that produced equipressor responses the least potent isomer produced the longest duration of effect. Using equipressor doses, the rate of development of tachyphylaxis was D(-)-ephedrlne < L(+)-ephedrine D(+)-amphetamine L(+)-pseudoephedrine. Animals made completely tachyphylactic to L (+) -ephedrine, D (+) -amphetamine and L(+)-pseudoephedrine still showed pressor effects to an injection of D(-)-ephedrine. No tachyphylaxis was observed to the depressor effect of D (-)-pseudoephedrine.

In the isolated perfused rabbit heart the relative chronotropic potencies of D (-) -ephedrine, L(+)-ephedrine and L(+)-pseudoephedrlne were approximately 100, 20 and 25, respectively. D (-) -Pseudoephedrine over a wide range of doses caused only a slight increase in rate, and effects were always submaximal. In reserpine pretreated dogs, increased blood pressure and heart rate effects of the isomers were markedly reduced. This reduction was reversible by increased dosage in the case of D (-) -ephedrine,but irreversible for L(+)-ephedrine and L(+)-pseudoephedrine. In spinal cats the pressor effect of D (-) -pseudoephedrine was reduced by reserpinization. D-Configuration of the beta-carbon in the ephedrines favors direct action while L- configuration favors indirect action.

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