Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia.

Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl D-aspartate-receptor. Mounting evidence indicate that the compound is significantly involved in basal neurophysiological processes in the brain. In the present investigation, cerebrospinal fluid (CSF) level of kynurenic acid was analyzed in 28 male schizophrenic patients and 17 male healthy controls by means of high pressure liquid chromatography and fluorescence detection. Schizophrenic patients showed elevated CSF levels of kynurenic acid (1.67+/-0.27 nM) compared to the control group (0.97+/-0.07 nM). Furthermore, CSF levels of kynurenic acid in schizophrenic patients were also found to correlate with age. The present finding is indicative of a contribution of kynurenic acid in the pathogenesis of schizophrenia.

Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report.

A 35-year-old man with schizophrenia was successfully treated with clozapine at a daily oral dose of 700-725 mg for more than 7 consecutive years. Two weeks after abrupt cessation of chronic heavy cigarette smoking, he suddenly developed tonic clonic seizures followed by stupor and coma. After 2 days of intensive care, the patient recovered completely but could not recall the episode. Clozapine therapy was reinstituted and could be carried out successfully at 425 mg daily, i.e., at an approximately 40% reduction of the daily dose before he stopped smoking. The sudden cessation of smoking most likely caused a rise in plasma concentrations of clozapine and/or clozapine metabolites resulting in the seizure episode. A likely mechanism is that the heavy smoking had induced cytochrome P450-1A2, the main enzyme involved in the metabolism of clozapine.