AUTONOMIC EFFECTS OF SELEGILINE - POSSIBLE CARDIOVASCULAR TOXICITY INPARKINSONS-DISEASE

Objectives-The United Kingdom Parkinson's Disease Research Group (UKPD RG) trial found an increased mortality in patients with Parkinson's di sease randomised to receive selegiline (10 mg/day) and levodopa compar ed with those taking levodopa alone. Unwanted effects of selegiline on cardiovascular regulation have been investigated as a potential cause for the unexpected mortality finding of the UKPDRG trial. Methods-The cardiovascular responses to a range of physiological stimuli, includi ng standing and head up tilt, were studied in patients with Parkinson' s disease receiving levodopa alone and a matched group on levodopa and selegiline. Results-Head up tilt caused selective and often severe or thostatic hypotension in nine of 16 patients taking selegiline and lev odopa, but was without effect on nine patients receiving levodopa alon e. Two patients taking selegiline lost consciousness with unrecordable blood pressures and a further four had severe symptomatic hypotension . The normal protective rises in heart rate and plasma noradrenaline w ere impaired. The abnormal response to head up tilt was reversed by di scontinuation of selegiline. Drug withdrawal caused a pronounced deter ioration in motor function in 13 of the 16 patients taking selegiline. Conclusion-Therapy with selegiline and levodopa in combination may be associated with severe orthostatic hypotension not attributable to le vodopa alone. Selegiline also has pronounced symptomatic motor effects in advanced Parkinson's disease. The possibilities that these cardiov ascular and motor findings might be due either to non-selective inhibi tion of monoamine oxidase or to amphetamine and met-amphetamine are di scussed.