Drugs Aging 2005; 22 (1): 93-94GUEST COMMENTARIES 1170-229X/05/0001-0093/$34.95/0

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This effect has been avoided in the trial designs ofRasagilinerasagiline. But objective measures of neuroprotec-A Viewpoint by Roger Barkertion outside of clinical rating scales would be more

Department of Neurology and Cambridgepowerful evidence to support such claims ofCentre for Brain Repair, Addenbrooke’sneuroprotection, especially given the great difficultyHospital, Cambridge, UKin extrapolating from in vitro cultures and pooranimal models of the disease. However, what consti-There are two major therapeutic challenges in thetutes such a measure is, at the present time, far frommodern management of Parkinson’s disease:clear, given the recent controversies with dopamine• What can be used to slow down disease progres-agonists and functional imaging in early Parkinson’ssion (neuroprotection)?disease to measure dopaminergic striatal tone. Nev-

• How can one best treat the more advanced stagesertheless, the data, at least at this stage, look encour-of disease where dyskinesia and ‘on’-‘off’aging, especially given the excellent tolerability pro-problems dominate the clinical picture?file of this drug.

It is in this context that the new drug, rasagiline,The second area of use is less contentious andhas to be seen. This agent is an irreversible inhibitor

there are certainly emerging data to strongly supportof monoamine-oxidase type B, and so is similar toselegiline, but with greater potency and less am- the use of this drug to help with the dyskinesias ofphetamine-like breakdown products. It is therefore advanced Parkinson’s disease. The use of an agentnot surprising that this drug has now been used in to improve and smooth out the delivery of levodopa-early-stage Parkinson’s disease as a possible derived dopamine to CNS receptors is an importantneuroprotective agent and as an adjunct to smooth

addition to the management of this aspect of Parkin-out control in advanced Parkinson’s disease. In both

son’s disease. However, the extent to which this caninstances, it seems to be beneficial, at least with thebe maintained, given the relative inflexibility of thedata to date.dosage regimen of this drug, is yet to be established, The neuroprotective properties of rasagiline areas is its long-term tolerability profile — especiallyof particular interest, especially given the history ofwhen one remembers what happened with the cat-selegiline and the recent dopamine agonist trialsechol-O-methyl transferase inhibitor tolcapone.exploring this aspect of Parkinson’s disease treat-

ment. In the case of selegiline, the initial in vitro and Overall, rasagiline is an attractive, potentiallyin vivo studies suggested a neuroprotective action, far-reaching, new agent in the management ofbut later analysis of the data, compounded by the

Parkinson’s disease and, I anticipate, it will becomeunexpected findings of a UK study, suggested that

widely used in both early- and late-stage disease.the drug provided a symptomatic improvement▲without producing a true neuroprotective effect.