Central nervous system depressant actions of clonidine and UK-14,304: partial dissociation of EEG and behavioural effects.

The effects in five normal subjects of a single dose of clonidine (300 μg), UK-14,304 (750 μg) and placebo on a subjective rating scale for alertness/sleepiness, the contingent negative variation (CNV), reaction time, blood pressure and heart rate were compared over 6 h in a double-blind study. After both drugs there was a fall in systolic and diastolic blood pressure and in heart rate. These changes were maximal between 2 and 4 h and were greater after clonidine than after UK-14,304. There was a progressive increase in subjective ratings of sleepiness after both drugs, commencing at 1 h and maximal between 2 and 4 h. This effect was more pronounced after clonidine than after UK-14,304. There was a close correlation between the fall in blood pressure and the change in subjective rating for sleepiness after both drugs. Behavioural sleep also occurred after both drugs. Compared with placebo there was a decrease in CNV magnitude at 2 and 4 h after both drugs, associated with a lengthening of reaction time and consistent with the subjective and behavioural changes. Depression of CNV magnitude was more pronounced after clonidine than after UK-14,304. In some subjects after both drugs there was an initial increase in CNV magnitude at 1.5 h, occurring at the same time as behavioural sleep and subjective ratings of sleepiness. Such a dissociation between CNV magnitude and subjective and behavioural effects of drugs in man has not previously been reported. It was concluded that UK-14,304 causes less central nervous system depression than clonidine at this dosage, but also has a less marked hypotensive effect.