’(ICI 204,636) is a dibenzothiazepine derivative in development as an atypical antipsychotic agent. ICI 204,636 exhibits high affinity for brain 5HT2(Ki = 151 nM) receptors and lower affinity for D1(Ki = 994) and D2(Ki = 194) receptors. In two trials involving the determination of neurocognitive effects of ICI 204,636, 18 men aged 24 to 58 years meeting DSM-IV criteria for schizophrenia, schizoaffective disorder, or bipolar disorder were studied. After withdrawal of antipsychotic medication, placebo was given tid single-blind for 4 to 9 days, then ICI 204,636 for 8 to 10 days, with dose escalated from 25 to 250 mg tid. ICI 204,636 was well tolerated with no withdrawals during ICI 204,636 administration. A computerized neurocognitive test battery was administered 0.5 hours before or 1.5 hours after the last morning placebo and ICI 204,636 dose. Repeated measures, within subject analysis of variance, were conducted on results. ICI 204,636 significantly improved performances on tests of attention and learning [Digit-Symbol Substitution; df (1, 13), F = 7.9, p < 0.01]; tasks involving speed and set shifting [Trails B; df (1, 13), F = 6.6, p < 0.02]; conflict-reaction-time measures, necessitating the inhibition of a predominant response [PRE A-Conflict Reaction Time; df (1, 10), Ft = 6.9, p < 0.02]; and response rate to an external stimulus [PRE A-Movement Time; df (1, 10), F = 4.7, p = 0.05]. ICI 204,636 treatment, therefore, significantly improved certain psychomotor and complex cognitive measures. ’is a trademark, the property of Zeneca Ltd.