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 tonic suppression of plasma aldosterone levels in human subjects. This action, however, had not been established directly using dopamine and dopamine mimetic drugs, which do not, in fact, affect the aldosterone levels. Rather, the conclusion was arrived at indirectly, based on the increase in aldosterone levels seen with dopamine receptor blockers; metoclopramide in particular, considered at the time of its discovery in the 1960s to be a new generation dopamine antagonist. However, metoclopramide is not a pure drug and in fact, shows intermediate affinity at certain serotonin receptor subtypes. Studies have been recently carried out in human subjects on the role of serotonergic transmission in mediating the metoclopramide as an aldosterone secretagogue effect. Here we briefly review this work and attempt to reassess the action of metoclopramide as an aldosterone secretagogue, from dopamine D2 antagonism to serotonin 5-HT4 partial agonism.
Rizzi
C A
CA
Medical Division, Boehringer Ingelheim, Milan, Italy.
Mierau
J
J
Ladinsky
H
H
D000450:Aldosterone / Q000097:blood*; D000818:Animals; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008787:Metoclopramide / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D012701:Serotonin / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*
D018492:Dopamine Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D000450:Aldosterone; D008787:Metoclopramide; D004298:Dopamine