The cardiovascular effects of metoclopramide in multiple system atrophy and pure autonomic failure

Metoclopramide (MCP), a central and peripheral dopaminergic blocker with ch olinergic activity, has been proposed to treat orthostatic hypotension (OH) on the basis that it could antagonize the vasodilator and natriuretic effe cts of dopamine. The authors evaluated cardiovascular responses to MCP in 1 1 subjects with OH: 6 with multiple system atrophy (MSA) and 5 with pure au tonomic failure (PAF), along with 6 healthy control subjects. Supine blood pressure (BP), heart rate (HR), and breathing were continuously monitored b efore, during, and after MCP infusion. The pre-MCP head-up tilt test was to lerated at 65 degrees for 10 minutes in all subjects except in one with PAF , who tolerated 30 degrees for only 5 minutes. Tilting confirmed the OH in patients with MSA (change in mean arterial pressure [Delta MAP] = -31 +/- 1 3 mm Hg) and PAF (Delta MAP = -34 +/- 8 mm Hg). Infusion of MCP was given i n four 5-mg doses every 5 minutes, with the subject in a supine position. I nfusion of MCP induced the following effects: (1) A transient hypotensive e ffect occurred after each infusion in both patients and control subjects, t he fall in MAP being counteracted by an increase in HR in control subjects but not in patients; this acute MAP fall was more severe in patients. (2) A progressive reduction of MAP occurred during the test, which never returne d to preinfusion levels in patients; this effect was so pronounced in two P AF patients as to prevent them from receiving the last dose. Post-MCP tilti ng was tolerated in control subjects but in only in 5 MSA patients and 4 PA F patients. In those patients who tolerated the test, the MAP fall was simi lar to, or worse than, that before MCP (MSA: Delta MAP = -28 +/- 16 mm Hg; PAF: Delta MAP = -38 +/- 16 mm Hg). The cardiovascular effect of MCP in nor mal subjects was a transient hypotension counterbalanced by reflex tachycar dia. The lack of an HR increase and the progressive fall in supine BP in MS A and PAY patients, together with worsening orthostatic tolerance after MCP infusion, are effects that should strongly discourage the use of this drug in the treatment of OH.