1 Three double-blind studies in young normotensive male volunteers were carried out: a study in ten awake subjects, comparing guanfacine 2.0 and 4.0 mg with clonidine 0.15 and 0.30 mg and placebo; and two polygraphic sleep studies each with six subjects, comparing guanfacine 1.0 and 2.0 mg with-placebo, and clonidine 0.15 and 0.30 mg with placebo, respectively. 2 In awake subjects, both drugs reduced systolic blood pressure without significantly altering diastolic blood pressure, pulse rate and objective performance parameters. 'Side-effects' such as tiredness, decreased inclination to work, and dryness of the mouth were somewhat more frequent after the higher clonidine dose than after both doses of guanfacine, and peaked 2 h after clonidine but only 4-6 h after guanfacine. 3 Clonidine 0.15 and 0.30 mg given in the evening was followed by a substantial and dosedependent reduction in rapid eye movement (REM) sleep. Guanfacine 1.0 mg did not alter REM sleep and 2.0 mg of guanfacine had less effect than both doses of clonidine in this respect. Clonidine's effect on REM sleep began after about 2 h, whereas guanfacine's action on REM sleep began 5 h after the dose. 4 Guanfacine and clonidine possess a qualitatively similar pattern of activity with regard to the parameters studied; but the central effects are less pronounced and occur later after guanfacine than after clonidine in equiactive doses.

In 10 healthy volunteers the time course of cardiac beta-adrenoceptor blocking activity, plasma levels and cumulative urinary excretion of pindolol were compared during a 4-day course of pindolol 5 mg (Visken) t. d. s., and one tablet of pindolol 20 mg retard (Visken retard) once a day. After oral administration of the 20 mg retard tablet, plasma concentrations of pindolol higher than half the maximum value (1/2 Cp (tmax)) were maintained about 2.5 times as long as after administration of the conventional 5 mg tablet. This is evidence for an important and marked retardation of drug release. During treatment with pindolol 20 mg retard once daily, cardiac beta-adrenoceptor blockade, measured by the reduction in exercise-induced tachycardia and in the exercise-induced rise in systolic blood pressure, at almost all times throughout the 24 h period was at least as great as during treatment with pindolol 5 mg t. d. s. This suggests that patients successfully treated with pindolol 5 mg t. d. s. can be maintained with the same beta-adrenoceptor blockade by a single tablet of pindolol 20 mg retard once daily.

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This study is an investigation of the central effects of vasopressin in man, as this hormone proved able to modify learning processes in animals and was applied successfully to post-traumatic, amnesic patients. Electrophysiological techniques were used to assess the effects of lysine-vasopressin (LVP) given by nasal spray (7 and 14 IU) on night sleep pattern (12 subjects), auditory evoked potentials (AEP; 26 subjects), and contingent negative variation (CNV; 26 subjects). Night sleep EEG was not modified to a great extent: in particular REM sleep did not undergo any change after LVP. Nor were AEPs modified, either in the 6-hour period following drug administration or 1 week after; CNV, however, reacted in a significant manner 6 h after drug intake, and the modifications were still present after 1 week. LVP did not affect CNV amplitude itself but its evolution through time, as CNV habituation was prevented. Such effects are discussed with regard to the neurochemical mechanisms of vasopressin action and CNV genesis.