Haloperidol

Abstract: ANTIPSYCHOTIC drugs, or neuroleptics, are thought to act by blocking dopamine receptors in the nervous system1–4. Recent direct evidence, based on stereospecific binding assays, supports this hypothesis of antipsychotic drug action5–9. As only a few antipsychotic drugs had been tested for their effects on the binding of haloperidol5–8, the question remained whether all antipsychotic drugs, regardless of chemical structure, would block the stereospecific binding of haloperidol. We report here that all clinically effective antipsychotic drugs (tested so far) block the stereo-specific binding of 3H-haloperidol at concentrations which correlate directly with the clinical potencies.

Abstract: The effects of amphetamine, various phenothiazines and haloperidol on dopaminergic neurons in the substantia nigra and ventral tegmental area of the rat midbrain were studied in anesthetized and gallamine-paralyzed animals using a single unit recording technique. d -Amphetamine administered intravenously markedly decreased the spontaneous activity of dopaminergic neurons in the substantia nigra and ventral tegmental area. Antipsychotic phenothiazines and haloperidol increased the firing rate of these cells and reversed the d -amphetamine depression. Promethazin. a phenothiazine lacking antipsychotic efficacy, had no effect. In an experiment designed to correlate changes in firing rate with dopamine metabolism, neostriatal 3,4-dihydroxyphenylacetic acid concentrations were determined before and after administration of chlorpromazine (1.25 mg/kg), amphetamine (1.25 mg/kg) and promethazine (10 mg/kg). Neostriatal 3,4-dihydroxyphenylacetic acid was inceased by chlorpromazine,decreaed by amphetamine and unchanged by promethazine, thus paralleling the effects of these drugs on dopaminergic unit activity. These findings, together with our single unit recording results, are compatible with the neuronal feedback hypothesis orignally suggested as a mechanism by which these drugs might alter dopamine metabolism.

Abstract: Objective: The purpose ofthis study was to investigate the safety and efficacy of risperidone in the treatment ofschizophrenic patients and determine its optimal dose Method: This double-blind study included 388 schizophrenic patients drawn from 20 sites in the United States Patients were randomly assigned to 8 weeks’ treatment with placebo, one of four doses of risperidone (2, 6, 1 0, or 1 6 mg), or 20 mg ofhaloperidol daily Results: Clinical improvement (20% reduction in totalscores on the Positive and Negative Syndrome Scale for Schizophrenia) at the study end point was shown by 35% ofthe patients receiving 2 mg ofrisperidone, 57% receiving 6 mg, 40% receiving 1 0 mg, and 51 % receiving 1 6 mg; and by 30% receiving haloperidoland 22% receiving placebo Statistically significant differences in clinical improvement were found between 6 and 1 6 mg of risperidone versus placebo and versus haloperidol Positive symptom scores were significantly lower after 6, 10, and 1 6 mg of risperidone and 20 mg ofhaloperidol than placebo; negative symptom scores, however, were reduced significantly, compared with placebo, only after 6 and 1 6 mg ofrisperidone The incidence of extrapyramidal side effects (measured by the Extrapyramidal Symptom Rating Scale) was significantly higher in patients treated with 1 6 mg of risperidone or 20 mg of haloperidol than placebo The results indicate that the optimal daily dose ofrisperidone for most schizophrenic patients in this study was 6 mg; this dose was as effective as 1 6 mg, and the incidence of extrapyramidal symptoms in patients receiving 6 mg of risperidone was no higher than that in patients receiving placebo Conclusions: Risperidone is a safe antipsychotic that is effective against both the positive and negative symptoms of schizophrenia (AmJ Psychiatry 1994; 151:825-835)

Abstract: OBJECTIVE: Since all antipsychotics block dopamine D2 receptors, the authors investigated how well D2 receptor occupancy in vivo predicts clinical response, extrapyramidal side effects, and hyperprolactinemia. METHOD: In a double-blind study, 22 patients with first-episode schizophrenia were randomly assigned to 1.0 or 2.5 mg/day of haloperidol. After 2 weeks of treatment, D2 receptor occupancy was determined with [11C]raclopride and positron emission tomography, and clinical response, extrapyramidal side effects, and prolactin levels were measured. Patients who showed adequate responses continued taking their initial doses, those who did not respond had their doses increased to 5.0 mg/day, and evaluations were repeated at 4 weeks for all patients. RESULTS: The patients showed a wide range of D2 occupancy (38%–87%). The degree of receptor occupancy predicted clinical improvement, hyperprolactinemia, and extrapyramidal side effects. The likelihood of clinical response, hyperprolactinemia, and extrapyramida...