Portal de Periódicos da CAPES

Monoamine Oxidase Inhibitors in Parkinson’s Disease

1989; Springer Science+Business Media; Linguagem: Inglês

10.1007/978-3-642-73899-9_15

1865-0325

M. Sandler, Vivette Glover,

Neurotransmitter Receptor Influence on Behavior

Following the seminal discovery by Ehringer and Hornykiewicz (1960) of the nigrostriatal dopamine deficiency of Parkinson’s disease, one obvious therapeutic strategy was to inhibit monoamine oxidase (MAO), the major enzyme metabolizing it in human brain, in order to conserve the attenuated supply. Holzer and Hornykiewicz (1959) had previously shown that the MAO inhibitors, iproniazid and harmine, increase the dopamine content of rabbit brain. Harmine had, in fact, been used very early on for the treatment of parkinsonism (Behringer and Wilmanns 1929). Although this and related compounds are reversible MAO inhibitors (Nelson et al. 1979), the beneficial effect claimed for it may not have stemmed from this particular biochemical action; the related compound, harmalol, which was thought to have a similar therapeutic effect (Cooper and Gunn 1931), is a much less potent MAO inhibitor. Iproniazid and other nonselective irreversible MAO inhibitors were carefully considered in the early 1960s for the treatment of parkinsonism. However, their use as a single treatment did not appear to lead to any rise in brain dopamine (Bernheimer et al. 1963) and resulted in no more than modest clinical improvement (Rosen 1969). It therefore seemed more reasonable to treat affected subjects with an l-dopa-MAO inhibitor combination. Indeed, a number of groups who carried out such a trial noted beneficial results (e.g. Birkmayer and Hornykiewicz 1961, 1962; Mcgeer et al. 1961; Barbeau et al. 1962), although marginal benefit only was recorded by others (Hirschmann and Mayer 1964).