AIMS: To compare the autonomic, neuroendocrine and psychomotor effects of single doses of the 'atypical' antipsychotic clozapine and the 'classical' antipsychotic haloperidol, in healthy male volunteers. METHODS:Clozapine (50 mg), haloperidol (3 mg) and placebo were administered to 12 healthy male volunteers at weekly intervals, according to a balanced double-blind design. Resting pupil diameter, salivary output, heart rate, blood pressure, plasma prolactin concentration, critical flicker fusion frequency and subjective 'alertness', 'contentedness' and 'anxiety' were measured at baseline and 2, 3, 4 and 5 h after drug ingestion. Data were analysed by analysis of variance with individual comparisons (Dunnett's test) with a significance criterion of P < 0.05. RESULTS: Significant treatment effects (difference from placebo [mean, 95% CI] 5 h after drug ingestion) were as follows: clozapine reduced pupil diameter (mm; -3.02 [-3.56, -2.47]), salivary output (g; -0.34 [-0.60, -0.08]), mean arterial blood pressure (mm Hg; -8.7 [-14.3, -3.1]), critical flicker fusion frequency (Hz; -3.26 [-3.94, -2.58]), and subjectively-rated 'alertness' (mm; -20.94 [-29.21, -12.67]) and 'contentedness' (mm; -12.98 [-17.90, -8.06]), whereas haloperidol increased prolactin concentration (mU l(-1); 301.3 [196.7, 405.8]) and caused small reductions in pupil diameter (mm; -0.68 [-1.23, -0.14]), mean arterial blood pressure (mm Hg; -7.0 [-12.6, -1.4]) and critical flicker fusion frequency (Hz; -1.15 [-1.83, -0.47]). CONCLUSIONS: The effects of the antipsychotics are in agreement with their receptor binding profiles: alpha(1)-adrenoceptor blockade by clozapine may contribute to reductions in pupil diameter, salivation, mean arterial blood pressure and sedation, and muscarinic cholinoceptor blockade by the drug may underlie the reduction in salivation. Conversely, D(2) dopamine receptor blockade by haloperidol is likely to be responsible for the increase in prolactin secretion evoked by the drug.
RCT Entities:
AIMS: To compare the autonomic, neuroendocrine and psychomotor effects of single doses of the 'atypical' antipsychotic clozapine and the 'classical' antipsychotic haloperidol, in healthy male volunteers. METHODS:Clozapine (50 mg), haloperidol (3 mg) and placebo were administered to 12 healthy male volunteers at weekly intervals, according to a balanced double-blind design. Resting pupil diameter, salivary output, heart rate, blood pressure, plasma prolactin concentration, critical flicker fusion frequency and subjective 'alertness', 'contentedness' and 'anxiety' were measured at baseline and 2, 3, 4 and 5 h after drug ingestion. Data were analysed by analysis of variance with individual comparisons (Dunnett's test) with a significance criterion of P < 0.05. RESULTS: Significant treatment effects (difference from placebo [mean, 95% CI] 5 h after drug ingestion) were as follows: clozapine reduced pupil diameter (mm; -3.02 [-3.56, -2.47]), salivary output (g; -0.34 [-0.60, -0.08]), mean arterial blood pressure (mm Hg; -8.7 [-14.3, -3.1]), critical flicker fusion frequency (Hz; -3.26 [-3.94, -2.58]), and subjectively-rated 'alertness' (mm; -20.94 [-29.21, -12.67]) and 'contentedness' (mm; -12.98 [-17.90, -8.06]), whereas haloperidol increased prolactin concentration (mU l(-1); 301.3 [196.7, 405.8]) and caused small reductions in pupil diameter (mm; -0.68 [-1.23, -0.14]), mean arterial blood pressure (mm Hg; -7.0 [-12.6, -1.4]) and critical flicker fusion frequency (Hz; -1.15 [-1.83, -0.47]). CONCLUSIONS: The effects of the antipsychotics are in agreement with their receptor binding profiles: alpha(1)-adrenoceptor blockade by clozapine may contribute to reductions in pupil diameter, salivation, mean arterial blood pressure and sedation, and muscarinic cholinoceptor blockade by the drug may underlie the reduction in salivation. Conversely, D(2) dopamine receptor blockade by haloperidol is likely to be responsible for the increase in prolactin secretion evoked by the drug.
Authors: Jose de Leon; Francisco J Diaz; Richard C Josiassen; George M Simpson Journal: Eur Arch Psychiatry Clin Neurosci Date: 2004-10 Impact factor: 5.270