Metabolic defects caused by treatment with the tetrahydropyridine analog of haloperidol (HPTP), in baboons.
Mounting evidence suggests that compromised cellular energy production is a major contributor to idiopathic and drug-induced degenerative processes. Our interest in neurotoxins have prompted us to examine in the baboon the effects of HPTP, the tetrahydropyridine dehydration product of haloperidol, on urinary chemical markers that reflect defects in mitochondrial respiration. Urinary dicarboxylic acid and conjugate profiles, similar to those seen in humans with inborn errors of mitochondrial metabolism and toxin-induced Jamaican vomiting sickness (JVS) were observed in the treated baboons. We interpret these results as evidence that HPTP and/or HPTP metabolites inhibit mitochondrial respiration in the baboon and speculate that analogous effects may occur in haloperidol-treated individuals.
Mienie
L J
LJ
Department of Biochemistry, Potchefstroom University for Christian Higher Education, South Africa.
Bergh
J J
JJ
Van Staden
E
E
Steyn
S J
SJ
Pond
S M
SM
Castagnoli
N
N
Van der Schyf
C J
CJ
D000818:Animals; D003998:Dicarboxylic Acids / Q000652:urine*; D044927:Electron-Transferring Flavoproteins; D044943:Fatty Acid Desaturases / Q000172:deficiency; D005420:Flavoproteins / Q000378:metabolism; D005977:Glutarates / Q000652:urine; D005998:Glycine / Q000652:urine; D006220:Haloperidol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007506:Iron-Sulfur Proteins; D007700:Kinetics; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000172:deficiency; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010101:Oxygen Consumption / Q000187:drug effects*; D010215:Papio
D003998:Dicarboxylic Acids; D044927:Electron-Transferring Flavoproteins; D005420:Flavoproteins; D005977:Glutarates; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; C101091:4(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-1,2,3,6-tetrahydropyridine; D044943:Fatty Acid Desaturases; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; C035736:glutaric acid; D006220:Haloperidol; D005998:Glycine