The effects of caffeine and cyclizine alone and in combination, on performance tests and subjective ratings have been examined in two groups of twelve volunteer subjects using a balanced design for order of administration of treatments, a lactose control and with double-blind conditions. In the second study the electroencephalograph (EEG) was recorded after subjective ratings. Results were analysed by analysis of variance and values of P < 0.05 taken as significant. 2 Caffeine in doses of 75 to 300 mg increased auditory vigilance compared with lactose dummy. Auditory reaction times were shortened, tapping rates increased and subjects felt more alert. No changes occurred in short term memory, arithmetic or digit symbol substitutions. An increase in energy in the delta band (2.3-4Hz) occurred after caffeine 100 mg. 3 Cyclizine by contrast, produced few changes. Subjects were more alert after 25 mg and more sedated after 100 mg than after dummy. One test only showed impairment: arithmetic, after the 100 mg dose, which also increased energy in the delta frequency band. 4 Combinations of caffeine 100 mg with cyclizine 50 and 100 mg did not produce any subjective changes, or changes in performance tests, differing from lactose. At no time on any test did the performances after combinations of drugs differ from caffeine 100 mg. SPerformance after both combinations of caffeine and cyclizine differed from that after cyclizine 100 mg on the following tests: vigilance, arithmetic and reaction time, thus showing a tendency for the caffeine effect to predominate. Subjective ratings of sedation after combination of the drugs were intermediate between the ratings following caffeine and cyclizine administered alone.

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I The effects of amitriptyline, nortriptyline, protriptyline, and a chemically related potential antidepressant, BW247, on performance tests and subjective ratings were studied. 2 Two groups of twelve healthy subjects received drugs and lactose dummy in identical capsules at weekly intervals according to a balanced design, under double-blind conditions, and with standardized tests and environment. 3 Amitriptyline produced the most marked effects, with significant (P < 0.05) impairment in auditory vigilance after 6.25 mg. Auditory reaction time, tapping rate, arithmetic, and digit symbol substitutions were impaired by amitriptyline 12.5 and 25 mg and all doses produced increased ratings of mental sedation. The effects began 1.5 h after drug and lasted approximately 5 h. 4 Nortriptyline produced fewer effects which were later in onset. Tapping at 1.8 h and auditory vigilance at 3.5 to 4.5 h were impaired by nortriptyline 25 mg whereas reaction time was prolonged by both doses at 5 h. No change in rating ofmental sedation occurred. SNo significant change in performance or subjective ratings followed protriptyline 10 mg or BW247, 12.5 and 25 mg. 6 The findings are discussed in relation to the presence of secondary and tertiary amines on the side chain of the compounds, and their relative abilities to block neuronal uptake of noradrenaline and 5-hydroxytryptamine.

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Single oral doses of atropine, nortriptyline, procyclidine and lactose dummy were administered double-blind to eight healthy young subjects in a balanced, crossover study. Television pupillometry was used to measure the anticholinergic effects of these drugs on the pupil diameter in darkness and the reflex response to light flashes. The sensitivity of this method was compared with conventional autonomic function tests, viz. salivary secretion, radial pulse, forearm sweat gland activity and distance to visual near point. Visual analogue scales were used to obtain subjective measures of sedative drug effects. The expected inhibition of parasympathetic activity was found in most instances with two exceptions: firstly, that nortriptyline failed to affect the pupil despite causing a tachycardia and secondly, that procyclidine gave a bradycardia. The results are discussed with reference to the possible advantages of television pupillometry over conventional pupil measurement in the detection of anticholinergic drug effects.