Common properties for propargylamines of enhancing superoxide dismutase and catalase activities in the dopaminergic syst
(–)Deprenyl has been reported to prolong the life span of different animal species. Further, the drug effectively increases antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions. We have found th
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Summary. (- )Deprenyl has been reported to prolong the life span of different animal species. Further, the drug effectively increases antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) in brain dopaminergic regions . We have found that the effect of the drug on antioxidant enzyme activities is highly dose dependent, increasing with an increasing dose , however, a higher dose becomes less effective and an excessive dose becomes adversely effective. Most importantly, an optimal dose for the effect varies widely dep ending on animal species , strain, sex, age and duration of the treatment, which may at least partly explain discrepancies reported among different studies in the past. From the parallelism of the doseeffect relationship of the drug between life span extension and increasing endogenous antioxidant enzyme activity, we have suggested that the above two effects of (- )deprenyl may be causally related. This review summarizes our past series of studies and also reports our very recent observation that other propargylamines such as rasagiline and (R)-N-(2-heptyl)-N-methylpropagylamine (R-2HMP) also share the property of enhancing antioxidant enzyme activities . Further, our most recent study has found that these propargylamines increase antioxidant enzyme activities not only in brain dopaminergic regions but in extra-brain dopaminergic tissues such as the heart and kidne ys. These observations are discussed in relation to the life prolonging effect of (- )deprenyl reported in the past. Introduction (- )Deprenyl is a monoamine oxidase B (MAO B) inhibitor but possesses a variety of pharmacological effects such as neuroprotection, life span prolongation, anti-apoptotic effects , etc. (reviewed in Kitani et aI., 1999). Knoll, who was initially involved in the development of the drug as an
P. Riederer et al. (eds.), Advances in Research on Neurodegeneration © Springer-Verlag Wien 2000
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K. Kitani et aI.
antidepressant, later reported that old rats which were treated chronically with (- )deprenyl lived for a significantly longer period than saline treated control animals (Knoll , 1988). He further reported that 3-week consecutive s.c. injections of the drug significantly increased activities of superoxide dismutase (SOD) but not of catalase (CAT) in the rat striatum (Knoll, 1988). Some years later, however, he cast some doubt on the latter observation, since the enhancing effect of (- )deprenyl on SOD activities was not reproduced in another strain of rats (Knoll, 1989). Although a positive effect of ( - )deprenyl in prolonging the life span of animals including rats (Knoll, 1988; Milgram et al., 1990; Kitani et al., 1993), mice (Archer and Harrison, 1996), hamsters (Stoll et al., 1997) and dogs (Ruehl et al., 1997) has been reported in recent years, other studies have failed to demonstrate a significant effect of the life prolongation of animals by this drug (Bickford et al., 1997; Gallagher et al., 1998; Ingram et al., 1993; Piantanelli et al., 1994). Our group has been involv
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