Effects of sedative and non-sedative antihistamine drugs on prefrontal cortex activities: towards pharmacological near-infrared spectroscopy studies

Abstract

Histamine H1-receptor antagonists (antihistamines) are widely used for the treatment of allergic disorders in young children. It is well known that the newer antihistamine drugs elicit better performances of working memory and selective attention than the first-generation drugs in this class. However, the neural correlates of the poorer performances associated with the first-generation antihistamines remain relatively unknown. In this article, we review recent studies in our laboratory that examined the effects of antihistamine drugs on prefrontal cortex activities in adults and young children using near-infrared spectroscopy (NIRS), an emerging brain imaging method that is suitable for psychological experiments. In the first study, we examined the prefrontal cortex activities while adult subjects performed a working memory task at 3 hours after taking a first-generation antihistamine (ketotifen), a second-generation antihistamine (epinastine), or a placebo. We found that cortical activation at the lateral prefrontal region increased during the performance of the working memory task in subjects administered epinastine or the placebo but not in those administered ketotifen. In the second study conducted in 15 healthy pre-school children (mean age: 5.5 years), ketotifen significantly impaired the behavioural performance and cortical activation at the lateral prefrontal cortex in a working memory task compared with epinastine and the placebo. In the third study conducted in school-aged children (mean age: 7.7 years), ketotifen significantly impaired the behavioural performance and cortical activation at the lateral prefrontal cortex compared with the placebo. There were no sedative effects on the neural responses or behavioural performance after epinastine administration. These studies demonstrate for the first time the differential sedation effects of first- and second-generation antihistamines on brain haemodynamic responses in young children. We also discuss the utility of the NIRS technique in psychopharmacological studies of children.