A COMPARISON OF THE CENTRAL-NERVOUS-SYSTEM EFFECTS OF HALOPERIDOL, CHLORPROMAZINE AND SULPIRIDE IN NORMAL VOLUNTEERS

1. Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti‐psychotic drugs: chlorpromazine (50 mg), haloperidol (3 mg), sulpiride (400 mg) and placebo. Drugs were allocated to subjects in a double‐blind, crossover fashion. 2. The subject's mood state, psychometric performance and electroencephalogram (EEG) were assessed pre‐dose, and at 2, 4, 6, 8, 24 and 48 h post‐dose. Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests: elapsed time estimation, tapping rate, choice reaction times, a rapid information processing task, flash fusion threshold, a manipulative motor task, digit span, body sway and tremor. 3. Chlorpromazine and haloperidol significantly reduced subjective ratings of ‘alertness’ and ‘contentedness’, and haloperidol significantly reduced feelings of ‘calmness’. Sulpiride did not significantly affect any of the visual analogue scales. 4. All three anti‐psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose. The profile was characterised by an increase in the proportion of slow wave activity (delta and theta) as well as decreased alpha (8‐14 Hz) and faster (beta) wave activity. 5. Chlorpromazine reduced tapping rate and increased choice reaction movement times. Haloperidol reduced the flash fusion threshold frequency at 6 h post‐ dose. Sulpiride prolonged the duration of the manipulative motor task, particularly at 48 h post‐dose. 6. All three anti‐psychotic drugs impaired performance on the rapid information processing task. Chlorpromazine significantly reduced the number of correct letter pair identifications at 2, 4 and 6 h post‐dose, haloperidol at 4, 6, 8, 24 and 48 h post‐dose, and sulpiride at 24 h post‐dose.(ABSTRACT TRUNCATED AT 250 WORDS) 1990 The British Pharmacological Society