EFFECT OF XAMOTEROL IN SHY-DRAGER SYNDROME

Background. Xamoterol, a cardioselective beta-1-adrenoceptor partial agonist, has been reported to be effective on postural hypotension. We investigated the effect of xamoterol in five patients with Shy-Drager syndrome (SDS) in relation to their prevailing sympathetic nerve activity and sensitivity of beta-adrenoceptors and the change in circadian variation of blood pressure. Methods and Results. Ambulatory blood pressure over 24 hours was monitored by noninvasive sphygmomanometer (model 5200, Spacelab). Plasma norepinephrine levels of SDS patients were significantly lower than that of normal subjects (n = 5) both at rest (54 +/- 15 versus 178 +/- 83 pg/ml) and after 10-minute standing (74 +/- 24 versus 318 +/- 143 pg/ml). Infusion of isoproterenol (0.02-mu-g/kg/min) produced a mild rise of systolic blood pressure and tachycardia in normal subjects but resulted in marked hypotension and tachycardia in SDS subjects. After xamoterol administration (200 mg b.i.d.), systolic blood pressure and heart rate, were significantly increased in the averages during the day; however, increases were more pronounced at night. In two of the five patients, the improvement in dizziness was large enough to enable them to increase their daily activities. Conclusions. Our observations suggest that 1) beta-1-selective, high intrinsic sympathomimetic activity of xamoterol increases blood pressure and heart rate in patients with SDS as a consequence of their prevailing beta-1-adrenoceptor hypersensitive state, and 2) blood pressure monitoring over 24 hours appears to have important advantages in evaluating the therapeutic effects on postural hypotension.