L-deprenyl confers specific protection against MPTP-induced Parkinson's disease-like movement disorder in the goldfish.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, accumulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of movement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectively. The mechanism by which MPTP causes reduced movement in goldfish is to cause an increase in resting time. Otherwise normal average velocity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity during times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and l-deprenyl is used for treatment of Parkinson's disease in humans. Therefore it is suggested that the evolutionarily equivalent subcortical circuitry and neural density of the goldfish brain may provide a useful model upon which to search for drugs relevant to human Parkinson's disease.
Adeyemo
O M
OM
Laboratory of Cell Biology and Genetics, N.I.D.D.K., National Institute of Health, Bethesda, MD 20892.
Youdim
M B
MB
Markey
S P
SP
Markey
C J
CJ
Pollard
H B
HB
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003010:Clorgyline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006054:Goldfish; D020267:MPTP Poisoning; D008995:Monoamine Oxidase / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D012642:Selegiline / Q000494:pharmacology*
D012642:Selegiline; D008995:Monoamine Oxidase; D003010:Clorgyline; D004298:Dopamine; D009638:Norepinephrine