Common properties for propargylamines of enhancing superoxide dismutase and catalase activities in the dopaminergic system in the rat: implications for the life prolonging effect of (-)deprenyl.
(-)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 depending 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 dose-effect 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 kidneys. These observations are discussed in relation to the life prolonging effect of (-)deprenyl reported in the past.
Kitani
K
K
National Institute for Longevity Sciences, Obu, Aichi, Japan. kitani@nils.go.jp
Minami
C
C
Maruyama
W
W
Kanai
S
S
Ivy
G O
GO
Carrillo
M C
MC
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism*; D004285:Dogs; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains / Q000378:metabolism; D010293:Pargyline / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011437:Propylamines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000378:metabolism*
D011437:Propylamines; C009054:propargylamine; D012642:Selegiline; D010293:Pargyline; D002374:Catalase; D013482:Superoxide Dismutase; D004298:Dopamine