REGULATION OF PLASMA-ALDOSTERONE LEVELS BY METOCLOPRAMIDE - A REAPPRAISAL OF ITS MECHANISM FROM DOPAMINERGIC ANTAGONISM TO SEROTONERGIC AGONISM

It has been thought, since the late 1970s, that, dopamine exerts a ton ic suppression of plasma aldosterone levels in human subjects. This ac tion, however, had not been established directly using dopamine and do pamine mimetic drugs, which do not, in fact, affect the aldosterone le vels. Rather, the conclusion was arrived at indirectly, based on the i ncrease in aldosterone levels seen with dopamine receptor blockers; me toclopramide in particular, considered at the time of its discovery in the 1960s to be a new generation dopamine antagonist. However, metocl opramide is not a pure drug and in fact, shows intermediate affinity a t certain serotonin receptor subtypes. Studies have been recently carr ied out in human subjects on the role of serotonergic transmission in mediating the metoclopramide secretagogue effect. Here we briefly revi ew this work and attempt to reassess the action of metoclopramide as a n aldosterone secretagogue, from dopamine D2 antagonism to serotonin 5 -HT4 partial agonism. (C) 1997 Elsevier Science Ltd.