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[ 3 H]1‐Methyl‐4‐Phenyl‐2,3‐Dihydropyridinium Ion Binding Sites in Mouse Brain: Pharmacological and Biological Characterization
Author(s) -
Zompo M.,
Ruiu S.,
Maggio R.,
Piccardi M. P.,
Corsini G. U.
Publication year - 1990
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1990.tb04889.x
Subject(s) - dopaminergic , monoamine oxidase , chemistry , enzyme , binding site , neuron , stereochemistry , dopamine , tyrosine hydroxylase , biochemistry , monoamine oxidase b , biology , neuroscience
Because 1‐methyl‐4‐phenyl‐2,3‐dihydropyridinium ion (MPP + ) appears to damage the dopaminergic neuron and cause neuronal death, we characterized [ 3 H]MPP + binding sites in mouse brain membranes. Among several compounds tested, debrisoquin [3,4‐dihydro‐2(1 H )‐isoquinolinecarboxamidine] and some analogues were able to antagonize [ 3 H]MPP + binding. Debrisoquin is able to block adrenergic transmission and inhibit the activity of monoamine oxidase A (MAO‐A). We found a certain correlation between the ability of these agents to displace [ 3 H]MPP + from its binding sites and their capacity to inhibit MAO‐A activity. These data and the finding of a higher number of [ 3 H]MPP + binding sites in human placenta compared to mouse brain suggest that these sites may correspond to MAO‐A enzymes. Recently it has been demonstrated in human brain that neurons in regions rich in catecholamines are positive for MAO‐A. Accordingly, we suggest MAO‐A as a possible accumulation site of MPP + within the dopaminergic neuron. We also indicate the chemical structural requirement associated with the best binding of debrisoquin analogues with [ 3 H]MPP + sites. It would be reasonable to test the effects of debrisoquinlike drugs able to pass the blood‐brain barrier on 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine toxicity.