Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers

Rationale: The human pupil may be a suitable physiological test system for the assessment of excessive daytime sleepiness (EDS), but pupillometric assessment could be confounded by medication for comorbid hypertension and mood disorders. Objectives: We examined the profile of the 5HT-2/α1/H1 antagonist ketanserin, the 5HT1a agonist buspirone and the beta adrenoceptor antagonist propranolol on pupillary and other measures of arousal. Materials and methods: Ketanserin (20 mg), buspirone (10 mg) and propranolol (40 mg) were administered in three independent experiments according to a crossover, placebo-controlled, double-blind design. Resting pupil diameter (RPD) was sampled over 5-min in darkness with infrared pupillometry. Tests also included critical flicker fusion frequency (CFFF), visual analogue scales (VAS), the pupillary light reflex and heart rate/blood pressure. Results: Ketanserin reduced RPD, CFFF, VAS-rated arousal and blood pressure and increased the light reflex amplitude. Buspirone reduced RPD and blood pressure. Propranolol reduced heart rate but had no effects on pupillary functions or any arousal measure. Conclusions: Ketanserin but not propranolol had a fully sedative profile and may confound pupillometric assessment of EDS. Beta adrenergic receptors do not appear to participate in arousal and pupillary functions, while 5HT1a receptors reduce pupil size without affecting arousal. Pupil size may not be used unequivocally as an index of the level of alertness in the case of drug-induced changes, when drugs interfere with the central pupil control mechanism in ways that are unrelated to their effects on arousal.