Ephedrine

Ephedrine is a naturally occurring sympathomimetic alkaloid (from Ephedra / má huáng) and a mixed-acting amine. It works mainly indirectly: taken up into noradrenergic nerve terminals by the norepinephrine transporter, it displaces norepinephrine from storage vesicles into the synapse, raising adrenergic tone throughout the body: its most potent measured action is as a norepinephrine-transporter (NET) substrate (EC50 ≈50 nM), with weaker substrate activity at the dopamine transporter. Direct receptor activity is comparatively negligible: a receptorome screen found only weak binding at α2-adrenergic and 5-HT7 receptors (Ki ≈1–10 µM) and no meaningful α1- or β-adrenoceptor activity, so its sympathomimetic effects are essentially all indirect, via the noradrenaline it releases. Because release rather than direct receptor potency drives the effect, tolerance (tachyphylaxis) develops as vesicular stores deplete. The result is a broad sympathomimetic profile: α1-mediated vasoconstriction raises blood pressure and shrinks nasal mucosa (decongestion). β1 stimulation increases heart rate and cardiac output. β2 stimulation relaxes bronchial smooth muscle (bronchodilation). It crosses into the CNS and is a mild stimulant: less potent and less euphoric than amphetamine, to which it is structurally related and for which it is a synthesis precursor. The medicinal drug is the (1R,2S)-(−)-erythro isomer (L-ephedrine). Its diastereomer pseudoephedrine (1S,2S) shares the peripheral decongestant use but has weaker central and pressor effects. Ephedrine is largely excreted unchanged by the kidneys, so its clearance depends on urine pH: acidic urine speeds elimination and shortens its action.