Riluzole and blood pressure in multiple system atrophy

Abstract.

Riluzole is a neuroprotective agent that is currently tested for the treatment of multiple system atrophy (MSA). Riluzole may influence afferent and efferent parts ofthe baroreflex due to glutamate antagonistic effects. The effect of riluzole on the efferent part may be unmasked in MSA patients with dysfunction of afferent structures ofthe baroreflex. We compared the effect of a single dose of 200 mg riluzole with placebo in 10 patients with probable MSA. Brachial blood pressure and heart rate were recorded at baseline and for 120 minutes every 5 minutes after ingestion ofr iluzole. For determination of spontaneous baroreflex sensitivity, continuous finger blood pressure and ECG were recorded. Cardiac stroke volume was monitored using impedance cardiography. The change in blood pressure over a two hour period was significantly greater with riluzole than with placebo (5 ± 5/2 ± 3 mmHg with placebo, 16 ± 6/10 ± 2mmHg with riluzole, p < 0.001 by ANOVA). Systemic vascular resistance increased 32 ± 6% with riluzole. Baroreflex sensitivity, the high and low frequency components of heart rate variability, and the low frequency component of systolic blood pressure variability were not different between placebo and riluzole treatment. We conclude that in MSA patients, manipulation of glutamatergic transmission with riluzole elicits a moderate pressor response. The response is explained by a marked increase in systemic vascular resistance. We propose that decreased inhibition ofef ferent sympathetic neurons may contribute to the response.