Comparative tolerability of the newer generation antiparkinsonian agents

In recent years, the treatment of Parkinson's disease has undergone an imme nse amount of research, resulting in the development of multiple new medica tions. This has largely been fuelled by dissatisfaction over the developmen t of motor complications secondary to long term levodopa therapy. Different treatment approaches are applied depending on the stage of Parkin son's disease. In early and mild Parkinson's disease, selegiline offers a l imited symptomatic effect. Its neuroprotective effect, although at present theoretical, has questionable clinical relevance,Increased mortality associ ated with selegiline has been reported, although a meta-analysis of 5 diffe rent trials did not support this finding. The newer, non-ergoline dopamine agonists, pramipexole and ropinirole, have undergone extensive studies to evaluate their efficacy as monotherapy in e arly Parkinson's disease. These newer agonists are ideal initial symptomati c medications, primarily because they delay the onset of levodopa-induced m otor fluctuations. Efficacy of the newer dopamine agonists in advanced dise ase seems to be comparable to that of the older agents, bromocriptine and p ergolide. Adverse effects can be reduced by starting the medication at a ve ry low dose and then slowly titrating upward. Catechol-O-methyl transferase (COMT) inhibitors are indicated for the treatment of meter fluctuations in advanced disease, particularly the `wearing-off' phenomenon. Tolcapone, a peripheral and central COMT inhibitor, appears to be quite effective, produ cing a 47% reduction in 'off' time. Unfortunately, 3 deaths have been obser ved, which are presumably secondary to tolcapone therapy. The drug has been withdrawn in many countries, and liver enzyme testing is mandatory in the US. Entacapone, a purely peripheral COMT inhibitor with a lower potency tha n tolcapone, has also proved to be effective and has net been associated wi th liver damage. obviating the need for testing.