Changes in the human light reflex as a measure of the anticholinergic effects of drugs. A comparison with other measures.

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.

Drowsiness, impaired performance and tricyclic antidepressants drugs.

1. The effects of amitriptyline, protriptyline, 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 standarized tests and environment. 3. Amitriptyline produced the most marked effects, with significant (P less than 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 of mental sedation occurred. 5. No 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.

The action of CNS drugs on an isolated sympathetic nerve preparation of rabbit.

The effect of some centrally active drugs on the transmission of nerve impulses through the isolated cervical sympathetic nerve and superior cervical ganglion of the rabbit has been studied by recording both preganglionic and ganglionic responses to single square wave stimuli. Chlorpromazine, trifluoperazine and haloperidol have a greater axonal depressant action than the known local anaesthetics procaine and xylocaine. Chlordiazepoxide and diazepam are similar in local anaesthetic potency to procaine while meprobamate and sodium pentobarbitone possess only slight axonal depressant properties. Meprobamate, sodium pentobarbitone and possibly diazepam have ganglion blocking properties while procaine, chlorpromazine, trifluoperazine, haloperidol and chlordiazepoxide reduce the ganglion potential by virtue of their preganglionic action.