Rm. Wu et al., NEURONAL PROTECTIVE AND RESCUE EFFECTS OF DEPRENYL AGAINST MPP(+) DOPAMINERGIC TOXICITY, Journal of neural transmission, 100(1), 1995, pp. 53-61
Intranigral infusion of 1-Methyl-4-phenylpyridinium ion (MPP(+), 2.1-1
6.8 nmol) dose-dependently injured nigral neurons as reflected by redu
ced dopamine levels in the ipsilateral striatum four days after the in
fusion of this toxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydr
opyridine (MPTP). Coadministration of deprenyl (4.2 nmol) with MPP(+)
into the substantia nigra protected against MPP(+)-induced moderate (2
0-50%) but not severe (over 70%) nigral injury as reflected in striata
l dopamine reductions. However, supplementary treatment with deprenyl
(0.25 mg/kg, s.c., twice daily for 4 days) after intranigral infusion
of MPP(+) significantly rescued nigral neurons from more severe damage
caused by a higher MPP(+) does (8.4 nmol) manifested by a lesser stri
atal dopamine decrease (-31%) compared to the non-deprenyl treated gro
up (-70%). Thus, in addition to the blockade of bioactivation of MPTP,
deprenyl can protect and/or rescue nigral neurons from MPP(+)-induced
dopaminergic neurotoxicity. These in vivo data add further evidence t
o suggest that deprenyl, a putative and clinically unproven neuroprote
ctive agent, may be of value in slowing the progressive nigral degener
ation in ''early'' Parkinson's disease, but may prove to be less so in
its terminal stages.