Ephedrine: direct, indirect or mixed acting sympathomimetic?

Ephedrine is the principal alkaloid that is responsible for the physiological effects of herb ephedra. This herb is found in literature of India and China since ancient times because of its effectiveness as an anti-asthmatic. Ephedrine is classified as sympathomimetic drug. Despite extensive work in this field, the mechanism of action of ephedrine remains controversial. Initial studies classified ephedrine as indirectly acting sympathomimetic, subsequent studies showed ephedrine acts by mixed action by releasing noradrenaline and by acting directly on receptors. However, few recent studies on rat have shown predominant direct action on adrenergic receptors. Hence, there is marked controversy existing whether ephedrine is directly, indirectly or mixed acting drug.