Selegiline monotherapy in the treatment of Parkinson's disease.

Abstract

The neurochemical basis of Parkinson's disease (PD) is a reduction of striatal dopamine. A major enzyme responsible for metabolizing dopamine in the brain is monoamine oxidase (MAO). Therefore, a logical approach is to inhibit MAO in an attempt to conserve endogenous dopamine. Nonselective, irreversible MAO inhibitors as monotherapy have shown a minimal clinical effect in PD. [1] When these drugs are combined with levodopa, a beneficial effect occurs; however, a marked rise in blood pressure results (the tyramine or cheese effect). [2-4] Therefore, this combination therapy has been abandoned. MAO has since been discovered to exist in two forms, initially defined by their sensitivity to the inhibiting drug clorgyline, with type A being more sensitive than type B. [5] MAO found in the brain is predominantly type B, while MAO in the gut is mainly type A. [6] Brain dopamine may be predominantly metabolized by MAO-B, but the possible importance of intraneuronal MAO-A in the brain should be considered. A new class of MAO inhibitors has been developed [7,8] that are selective, irreversible inhibitors of MAO-B, thus able to preserve endogenous and exogenous dopamine without the MAO-A mediated cheese effect. One of these drugs, isopropylmethylpropargylamine hydrochloride, known as deprenyl or selegiline, has undergone further clinical development. Since deprenyl blocks MAO-B in the brain, it was thought that endogenous dopamine could be increased, resulting in symptomatic improvement. Bhatin et al. [9] studied deprenyl in 20 PD patients who were in the early phase of the disease and initially noted improvement in clinical scores, followed by subsequent worsening. They concluded that deprenyl may have a short-lasting symptomatic effect. The French selegiline multicenter trial [10] investigated whether the disability of de novo patients with parkinsonism could be improved during the first 3 months by deprenyl monotherapy (10 mg/day). The double-blind, randomized, placebo-controlled trial …