Analysis of the metabolism of haloperidol and its neurotoxic pyridinium metabolite in patients with drug-induced parkinsonism.
The blood levels of the neurotrophic drug haloperidol (HP) and its pyridinium metabolite, HPP(+), have been analyzed by liquid chromatography/electrospray ionization-mass spectrometry in 10 schizophrenic patients treated with HP, without carbamazepine (HP, oral daily dose of 0.3-0.5 mg/kg body weight for more than 1 year, females, aged 41 +/- 8.5 years). There was a significant difference (t-test, d.f. = 8, p (t(0) = 7.2) <0.005) in the blood HPP(+) level between the 5 patients with (18.5 +/- 6.4 ng/ml) and the 5 without (6.3 +/- 2.4 ng/ml) severe side effects such as drug-induced parkinsonism (Extrapyramidal Symptom Rating Scale (ESRS) parkinsonism severity scores 2.8 +/- 1.5 and 1.8 +/- 1.1, respectively). Moreover, it is suggested that vitamin E may be effective for drug-induced parkinsonism through a change in the blood HPP(+) level. It is necessary to investigate the HPP(+) metabolism in psychiatric patients to avoid severe side effects such as drug-induced parkinsonism and cardiac functional disorders.
Iwahashi
K
K
Health Administration Center, Department of Physiology, Azabu University, Sagamihara City, Kanagawa, Japan. iwahashi@azabu-u.ac.jp
Anemo
K
K
Nakamura
K
K
Fukunishi
I
I
Igarashi
K
K
D000328:Adult; D014150:Antipsychotic Agents / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D006220:Haloperidol / Q000097:blood*; D006801:Humans; D020734:Parkinsonian Disorders / Q000097:blood* / Q000139:chemically induced*; D011726:Pyridinium Compounds / Q000097:blood* / Q000633:toxicity*; D012559:Schizophrenia / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization
D014150:Antipsychotic Agents; D011726:Pyridinium Compounds; D006220:Haloperidol