meta-Hydroxyephedrine, also known as 3-hydroxyephedrine (HED), amongst other names, is a reuptake inhibitor and, at the same time, a substrate (HED is transported into adrenergic neurons) for the norepinephrine transporter; it inhibits the dopamine transporter to a fairly small extent and has a minor effect on VMAT2 vesicular uptake.
Pharmacology HED exists in the form of four stereoisomers; at least each of them exhibits different potency towards the biological target, generally, the 1R-diastereomers are more active than the 1S-diastereomers; the potency of action in inhibiting NET can be described as 1R,2S > 1S,2S = 1S,2R > 1R,2R; the values were measured as IC50, for the four isomers, the values were 0.422 ± 0.04, 1.03 ± 0.10, 1.18 ± 0.26 and 6.95 ± 1.1 µM respectively, making the 1R,2R isomer the weakest in terms of binding affinity.
They also inhibit DAT and VMAT2 and have very weak inhibitory effects on SERT; interestingly, the most potent isomer is not selective, 1S,2R HED showed the highest selectivity for NET compared with the dopamine transporter and VMAT2; nevertheless, 1R,2S HED is also more effective at inhibiting DAT and VMAT2, with IC50 values of 4.34 ± 1.4 and 23.7 ± 2.2 µM for 1R,2S isomer respectively, whilst 1S,2R HED was again very weak at inhibiting DAT (43.2 ± 5.7 µM) but was effective at inhibiting VMAT2, in contrast to 1R,2R HED, which had the poorest inhibition value (144 ± 18 µM). For all isomers, the inhibition values for SERT were >30 µM.
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