The angiotensin converting enzyme (ACE) inhibitor, perindopril, modifies the clinical features of Parkinson's disease

Background: Animal studies have demonstrated an interaction within the stri atum between the angiotensin and dopaminergic systems. In rats, the angiote nsin converting enzyme (ACE) inhibitor, perindopril, crosses the blood brai n barrier and increases striatal dopamine synthesis and release. In humans, angiotensin type 1 receptors have been found on dopaminergic neurons in th e substantia nigra and striatum. In Parkinson's disease, there is a marked reduction of these receptors associated with the nigrostriatal dopaminergic neuron loss. Aims: We performed a double blind placebo controlled crossover pilot study in seven patients to investigate the effect of the ACE inhibitor, perindopr il on the clinical features of moderately severe Parkinson's disease. Results: After a four week treatment period with perindopril, patients had a faster onset in their motor response to L-dopa and a reduction in 'on pha se' peak dyskinesia, p=0.021 and p=0.014 respectively. Patients also report ed more 'on' periods during their waking day in their movement diary, p=0.0 07. Perindopril was well tolerated without any significant postural hypoten sion or renal dysfunction. Conclusions: These results suggest that ACE inhibitors such as perindopril may have a place in the management of motor fluctuations and dyskinesia in Parkinson's disease and justify further study.