I)( -)-Ephedrine is the only isomer of ephedrine which produces a marked contraction of rabbit aortic strips. In the presence of M concentrations of L( + )-ephedrine, L(+)-pseudoephedrine, or D( -)-pseudoephedrine, the dose-response curves of D( -)-ephedrine are shifted to the right.
On the isolated rat vas deferens D( -)-pseudoephedrine did not show any intrinsic effects. However, the contractions due to tyramine and D( -)ephedrine were markedly antagonized by lo-* M and M D(-)-pseudoephedrine, while the effects of norepinephrine were potentiated. In addition, D( -)-pseudoephedrine and D( -)-ephedrine also compete for the a-adrenergic sites in the reserpine pretreated animals. D( -)-Pseudoephedrine appears to act a t both the catecholamine uptake site and the or-adrenergic site, but apparently lacks intrinsic effects at the latter site.
By using receptor protectioii cxperirticiits, it was possible to demonstrate that D( -)-pseudoephedrine also competes for the a-adrenetgic sites However, this effect must be very weak because the effects of exogenous norepinephrine are potentiated (i.e., the competition of D(-))-pseudoephedrine at areceptors is overcome by norepinephrine, the uptake of which is being prevented in the nerve endings). Thus, D( -)-pseudoephedrine is capable of acting at the catecholamine uptake sites and the a-adrenergic sites; however, it lacks intrinsic activity at the latter site.
The pharmacological effects of L( + )-pseudoephedrine and L( + )-ephedrine are similar on the aortic strips which support the previous report that there is a small difference between the pressor eflects of these L-diastereoisoriiers in the dog (2).
SUMMARY
In anesthetized dogs, pretreatment (30 min.) with D( -)-pseudoephedrine, 3.3 mg./Kg., can reduce or block the pressor effects of D( -)-ephedrine, L(+)ephedrine, L( + )-pseudoephedrine, and amphetamine. D( -)-Pseudoephedrine also promptly reduces the pressor effects, if given during the height of response. The pressor effects of norepinephrine and epinephrine appeared to be potentiated by u( -)-pseudoephedrine. Such a potentiation was best seen 45 to 60 min. after the administration of the isomer. The pressor effects due to bilateral carotid occlusion were unaffected by D( -)-pseudoephedrine.