Selegiline

Another drug used in the treatment of Parkinson's disease is selegiline (also known as deprenyl, or Eldepryl). It is an irreversible inhibitor of MAO-B, an important enzyme in the metabolism of dopamine (Fig. 33.2). Blockade of dopamine metabolism makes more dopamine available for stimulation of its receptors. Selegiline, as monotherapy, may be effective in the newly diagnosed patient with parkinsonism because its pharmacological effect enhances the actions of endogenous dopamine.

Selegiline is also used in conjunction with levodopa-carbidopa in later-stage parkinsonism to reduce lev-odopa dosage requirements and to minimize or delay the onset of dyskinesias and motor fluctuations that usually accompany long-term treatment with levodopa. It has also been proposed that selegiline may slow the progression of the disease by reducing the formation of toxic free radicals produced during the metabolism of dopamine (Fig.31.2). However, any neuroprotective effect of selegiline in parkinsonian patients remains to be established.

Most of the adverse reactions to selegiline are related to actions of increased levels of dopamine, as discussed earlier. At recommended doses, and unlike the nonselective MAO inhibitors used in the treatment of depression, selegiline has little effect on MAO-A and therefore generally does not cause the hypertension associated with the ingestion of tyramine-enriched foods (see Chapter 20). However, at doses higher than those usually recommended, MAO-A may be inhibited, which increases the risk of a tyramine reaction.

Selegiline should not be coadministered with tricyclic antidepressants or selective serotonin uptake inhibitors because of the possibility of a severe adverse drug reaction (e.g., hyperpyrexia, agitation, delirium, coma).

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