Tissue concentrations of MPTP and MPP+ in relation to catecholamine depletion after the oral or subcutaneous administration of MPTP to mice.
One hour after MPTP was given to mice at a dose of 30 mg/kg s.c., its concentration in tissues varied in the order kidney greater than liver greater than lung greater than brain greater than heart. When the same dose of MPTP was given orally, concentrations in most tissues were much lower at 1 hr than after s.c. administration, although the MPTP concentration in liver was only slightly lower. The concentrations of MPP+ (a metabolite of MPTP) at 1 hr were as high or higher than those of MPTP in all tissues except kidney, and MPP+ disappeared from the various tissues with half-lives from 3-20 hrs. The highest concentrations of MPP+, both absolute and relative to MPTP, were in heart. After oral administration of MPTP, no MPP+ was found in brain, and MPP+ concentrations in other tissues were lower than those after s.c. dosing. The depletion of heart norepinephrine was similar after MPTP administration by either route of administration even though MPTP and MPP+ concentrations in heart were lower after oral administration, suggesting that other metabolites of MPTP might also contribute to heart norepinephrine depletion.
Fuller
R W
RW
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Hemrick-Luecke
S K
SK
Perry
K W
KW
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015655:1-Methyl-4-phenylpyridinium / Q000032:analysis* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D001923:Brain Chemistry; D002395:Catecholamines / Q000032:analysis*; D007279:Injections, Subcutaneous; D007668:Kidney / Q000032:analysis; D008099:Liver / Q000032:analysis; D008168:Lung / Q000032:analysis; D008297:Male; D051379:Mice; D009206:Myocardium / Q000032:analysis
D002395:Catecholamines; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium