Metabolic defects caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and by HPTP (the tetrahydropyridinyl analog of haloperidol), in rats.
The results of previous studies in the baboon have suggested that HPTP, the tetrahydropyridinyl analog of haloperidol causes a urinary biochemical marker profile similar to those seen in humans suffering from inborn errors of mitochondrial respiration. In order to identify a possible relationship between compromised cellular energy production and neuronal damage we now have compared the urinary profiles of rats treated with the pro-neurotoxin, MPTP as well as with HPTP. Significantly increased urinary excretion of lactic acid and 2-ethylhydracrylic acid in MPTP and HPTP treated rats was observed, indicating that both MPTP and HPTP and/or their respective metabolites cause mitochondrial inhibition in the rat.
Petzer
J P
JP
Department of Pharmaceutical Chemistry, Potchefstroom University for Christian Higher Education, South Africa.
Bergh
J J
JJ
Mienie
L J
LJ
Castagnoli
N
N
Van der Schyf
C J
CJ
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000493:pharmacokinetics; D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D019344:Lactic Acid / Q000652:urine; D008297:Male; D008661:Metabolism, Inborn Errors / Q000139:chemically induced*; D008928:Mitochondria / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014631:Valerates / Q000652:urine
D014150:Antipsychotic Agents; D014631:Valerates; D019344:Lactic Acid; C007674:2-ethylhydracrylic acid; C101091:4(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-1,2,3,6-tetrahydropyridine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D006220:Haloperidol