Movement Disorders zyxwvutsrqponmlk Vol. zyxwvutsrqponmlk 13, No. zyxwvutsrqpon 4, zyxwvutsrqpon 1998, pp. 673476 0 1998 Movement Disorder Society Efaroxan, an Alpha-2 Antagonist, in the Treatment of Progressive Supranuclear Palsy "Olivier Rascol, MD, PhD, IKasia Sieradzan, MD, PhD, 3HCl5ne Peyro-Saint-Paul, MD, *Claire Thalamas, MD, *Christine Brefel-Courbon, MD, *Jean Michel Senard, MD, PhD, 3Philippe Ladure, PhD, *Jean Louis Montastruc, MD, PhD, and ItAndrew Lees, MD, FRCP zyx *Departments zyxwvutsrq of Clinical Pharmacology, Neurology and Clinical Investigation Center, University Hospital, Toulouse, France; TDeparment of Neurology, Manchester Royal Infirmary, U. K.; Slnstitut de Recherche P. Fabre, Boulogne, France; and IlNational Hospital for Neurology and Neurosurgery, London, U.K. Summary: We have tested, in a prospective randomized, dnuble-blind, placebo-controlled, crossover, 12-week study, the effects of 2 mg efaroxan, a potent alpha-2 antagonist, given three times per day to 14 patients with progressive supranuclear palsy. Efaroxan did not induce any significant change on any motor assessment criteria. The present data do not confirm the assumption that the blockade of alpha-2 receptors might be a useful pharmacologic strategy to improve patients with pro- gressive supranuclear palsy. Key Words: Progressive supra- nuclear palsy-Clinical trial-Efaroxan-Alpha-2 antagonist. No effective therapy exists for progressive supra- nuclear palsy (PSP). Recently, however, Ghika and col- leagues' reported a series of nine PSP patients in whom an alpha-:! antagonist, idazoxan, proved to be signifi- cantly better than placebo in relieving extrapyramidal symptoms and signs. Efaroxan is a potent and selective alpha-2 adrenoreceptor antagonist in vitro' and in vivo.3 Similar to idazoxan, its overall effect is to increase nor- adrenaline release from central and postganglionic nerve endings through blockade of presynaptic alpha-2 recep- tor~.~ Compared with idazoxan, efaroxan is 10-15 times more potent in vitro5 and has no affinity on imidazoline binding sites in humans.6 Testing this drug in PSP pa- tients then offers the opportunity to assess a more potent and selective compound than idazoxan in terms of effi- cacy and tolerability. Thus, the aim of the present study was to assess, in a prospective placebo-controlled design, the efficacy and safety of efaroxan in PSP patients. Received October 28, 1997; revision received February 3, 1998. Accepted February zyxwvutsrqp 4, 1998. Address correspondence and reprint requests to Prof. Olivier Rascol at the Laboratoire de Pharmacologie MCdicale et Clinique, INSERM U.455, 37 A116es Jules Guesde, 31073 Toulouse Cedex, France. METHODS Patients aged 40-80 years were recruited in the study if they presented with a clinical diagnosis of PSP accord- ing to Lees et al. criteria7: a progressive nonfamilial dis- order beginning in middle or old age with a supranuclear ophthalmoplegia including downgaze abnormalities and at least two of the following five cardinal features: axial dystonia and rigidity, pseudobulbar palsy, bradykinesia and rigidity, frontal lobe signs, and postural instability with falls backward. Such patients were included if they were rated II-IV on the Hoehn and Yahr scale, if they had no sign of cerebrovascular disease on a brain com- puted tomography scan or magnetic resonance image, and if they were not severely demented according to the DSM-IV criteria.8 Patients with a history of hypertension were excluded. The only permitted symptomatic treat- ment was L-dopa being maintained at a stable dose 4 weeks before and during the whole study. Dopamine agonists, selegiline, antidepressants, neuroleptics, and sedative drugs were not permitted. The trial was a two-center (Toulouse, France and Lon- don, UK), randomized, double-blind, placebo-controlled, crossover, 12-week study. Both study periods consisted of 4 weeks of treatment with either efaroxan or placebo separated by a 2-week washout period. After the second period, patients were followed up without treatment for 2 673