Depletion of heart norepinephrine in mice by some analogs of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine).
The effects of ten analogs of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) on heart norepinephrine concentration in mice were compared to those of MPTP itself. A single dose of MPTP (10 mg/kg s.c.) caused 73% depletion of heart norepinephrine 24 hrs after its injection. m-Hydroxy-MPTP caused an identical degree of depletion, and six other analogs caused statistically significant but lesser depletion. Three analogs caused no significant change in heart norepinephrine concentration. Since MPTP is oxidized by type B monoamine oxidase (MAO-B), the analogs were compared for their ability to be oxidized by mitochondrial MAO preparations from mouse brain and liver. MPTP and seven analogs were oxidized by MAO-B (oxidation was inhibited by deprenyl); three analogs were not oxidized or were oxidized only slowly and not by MAO-B. The ability of the compounds to deplete heart norepinephrine paralleled their ability to deplete striatal dopamine in the case of MPTP and seven analogs. Three analogs--the same three that were not substrates for MAO-B--depleted heart norepinephrine but not striatal dopamine. One conclusion is that the ability of an MPTP analog to be a substrate for MAO-B is a necessary but not sufficient requirement for depletion of striatal dopamine, but is not necessary for depletion of heart norepinephrine.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000494:pharmacology*
D011725:Pyridines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D004298:Dopamine; D009638:Norepinephrine