Persistent depletion of striatal dopamine in mice by m-hydroxy-MPTP.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) caused marked depletion of dopamine and of its two metabolites, DOPAC (3,4-dihydroxyphenylacetic acid) and HVA (homovanillic acid) one week after the last of four daily s.c. injections (20 mg/kg) in mice. Norepinephrine concentration in the frontal cortex was also decreased. m-Hydroxy-MPTP at a higher dose (80 mg/kg s.c.) caused a similar degree of depletion of dopamine and its metabolites in striatum and of norepinephrine in frontal cortex. p-Hydroxy-MPTP and o-hydroxy-MPTP (both at 80 mg/kg s.c.) caused no significant change in striatal dopamine or in cortical norepinephrine concentrations and had little or no effect on the dopamine metabolites. The m-hydroxy analog increases the list of MPTP-like compounds known to cause persistent depletion of striatal dopamine, and the positional isomers of this compound illustrate the strict structural dependency of this effect.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D007536:Isomerism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009638:Norepinephrine / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; C050173:1-methyl-4-(3-hydroxyphenyl)-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid