Riluzole and blood pressure in multiple system atrophy

Abstract.  Riluzole is a neuroprotectiveagent that is currently testedfor the treatment of multiple systematrophy (MSA). Riluzole mayinfluence afferent and efferentparts ofthe baroreflex due to glutamateantagonistic effects. The effectof riluzole on the efferent partmay be unmasked in MSA patientswith dysfunction of afferent structuresofthe baroreflex. We comparedthe effect of a single dose of200 mg riluzole with placebo in 10patients with probable MSA.Brachial blood pressure and heartrate were recorded at baseline andfor 120 minutes every 5 minutes afteringestion ofr iluzole. For determinationof spontaneous baroreflexsensitivity, continuous fingerblood pressure and ECG wererecorded. Cardiac stroke volumewas monitored using impedancecardiography. The change in bloodpressure over a two hour periodwas significantly greater withriluzole than with placebo(5 ± 5/2 ± 3 mmHg with placebo,16 ± 6/10 ± 2mmHg with riluzole,p < 0.001 by ANOVA). Systemic vascularresistance increased 32 ± 6%with riluzole. Baroreflex sensitivity,the high and low frequency componentsof heart rate variability, andthe low frequency component ofsystolic blood pressure variabilitywere not different between placeboand riluzole treatment. We concludethat in MSA patients, manipulationof glutamatergic transmissionwith riluzole elicits amoderate pressor response. The responseis explained by a markedincrease in systemic vascular resistance.We propose that decreasedinhibition ofef ferent sympatheticneurons may contribute to the response.