PMID- 3928814
OWN - NLM
STAT- MEDLINE
DCOM- 19851011
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 45
IP  - 4
DP  - 1985 Oct
TI  - Studies on the oxidation of the dopaminergic neurotoxin 
      1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine by monoamine oxidase B.
PG  - 1049-54
AB  - 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is a chemical that, after 
      injection into experimental animals, including mice and monkeys, causes a 
      degeneration of the nigrostriatal pathway. We carried out experiments designed to 
      study the in vitro oxidation of MPTP by mouse brain mitochondrial preparations. 
      MPTP was actively oxidized by the mitochondrial preparations, with Km and Vmax 
      values very similar to those of benzylamine, a typical substrate for MAO-B. MPTP 
      was oxidized considerably better than many of its analogs, even those with 
      relatively minor structural changes. Several monoamine oxidase inhibitors (MAOI) 
      were potent inhibitors of MPTP oxidation, and there was a highly significant 
      correlation between the capacity of the MAOI tested to inhibit MPTP oxidation and 
      benzylamine oxidation. There was no correlation between the capacity of the MAOI 
      to inhibit MPTP oxidation and their capacity to inhibit the oxidation of 
      tryptamine, a substrate for MAO-A. In other experiments, MPTP was an excellent 
      substrate for pure MAO-B, prepared from bovine liver. All of these data, combined 
      with the fact that MAO-B inhibitors can protect against MPTP-induced dopaminergic 
      neurotoxicity in vivo, point to an important role for MAO-B in MPTP metabolism in 
      vivo.
FAU - Heikkila, R E
AU  - Heikkila RE
FAU - Manzino, L
AU  - Manzino L
FAU - Cabbat, F S
AU  - Cabbat FS
FAU - Duvoisin, R C
AU  - Duvoisin RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Benzylamines)
RN  - 0 (Indans)
RN  - 0 (Pyridines)
RN  - 0 (Tryptamines)
RN  - 003N66TS6T (rasagiline)
RN  - 2K1V7GP655 (Selegiline)
RN  - 422ZU9N5TV (tryptamine)
RN  - 48G762T011 (Allylamine)
RN  - 85278-66-6 (2-(3,4-dimethoxyphenyl)-3-fluoroallylamine)
RN  - 9P21XSP91P (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
RN  - A1O31ROR09 (benzylamine)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - LYJ16FZU9Q (Clorgyline)
SB  - IM
MH  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
MH  - Allylamine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Benzylamines/metabolism
MH  - Brain/ultrastructure
MH  - Clorgyline/pharmacology
MH  - Indans/pharmacology
MH  - Kinetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/enzymology
MH  - Monoamine Oxidase/*metabolism
MH  - Oxidation-Reduction
MH  - Pyridines/*metabolism
MH  - Selegiline/pharmacology
MH  - Tryptamines/metabolism
EDAT- 1985/10/01 00:00
MHDA- 1985/10/01 00:01
CRDT- 1985/10/01 00:00
PHST- 1985/10/01 00:00 [pubmed]
PHST- 1985/10/01 00:01 [medline]
PHST- 1985/10/01 00:00 [entrez]
AID - 10.1111/j.1471-4159.1985.tb05522.x [doi]
PST - ppublish
SO  - J Neurochem. 1985 Oct;45(4):1049-54. doi: 10.1111/j.1471-4159.1985.tb05522.x.