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 pr ocesses. Our interest in neurotoxins have prompted us to examine in th e baboon the effects of HPTP, the tetrahydropyridine dehydration produ ct of haloperidol, on urinary chemical markers that reflect defects in mitochondrial respiration. Urinary dicarboxylic acid and conjugate pr ofiles, similar to those seen in humans with inborn errors of mitochon drial metabolism and toxin-induced Jamaican vomiting sickness (JVS) we re observed in the treated baboons. We interpret these results as evid ence that HPTP and/or HPTP metabolites inhibit mitochondrial respirati on in the baboon and speculate that analogous effects may occur in hal operidol-treated individuals.