Effect of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydropyridine , an analog of MPTP, on mouse heart norepinephrine and brain catecholamines.
An analog of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) with a thiadiazole substituent in place of the phenyl ring was compared to MPTP in mice for its ability to deplete striatal dopamine and its metabolites and norepinephrine in the frontal cortex and heart. One week after the last of 4 daily s.c. injections, MPTP at 20 mg/kg depleted mouse striatal dopamine, DOPAC and HVA as well as norepinephrine in the frontal cortex. One week after 4 daily s.c. doses of 4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydro pyr idine (MZTP) at doses as high as 80 mg/kg, there was no effect on brain catecholamines. A single dose of MPTP (10 mg/kg s.c.) depleted heart norepinephrine concentration 24 h after injection. MZTP had no effect on heart norepinephrine at 10 mg/kg s.c., but did significantly deplete mouse heart norepinephrine 24 h after a dose of 20 mg/kg s.c.
Hemrick-Luecke
S K
SK
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285.
Mitch
C H
CH
Quimby
S J
SJ
Fuller
R W
RW
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; C084733:4-(4-methoxy-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid