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

Abstract

1 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.

2 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.

3 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.

4 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.

5 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.

6 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.