Effects of sedative and non-sedative H1 antagonists on cognitive tasks: behavioral and near-infrared spectroscopy (NIRS) examinations.
BACKGROUND
It is well known that the newer H1-receptor antagonists elicit better performance of working memory and selective attention relative to the first generation drugs in this class. However, the neural correlates of the poorer performance associated with first-generation H1-receptor antagonists remain unknown.


OBJECTIVE
This study examined the effects of first- and second-generation H1-receptor antagonists on neural correlates of cognitive tasks using near-infrared spectroscopy (NIRS), a novel method of brain imaging suitable for psychological experiments.


METHODS
We measured the NIRS responses of 12 healthy volunteer subjects during the performance of working memory, selective attention, and visual perception tasks, 3 h after taking a first-generation antagonist (ketotifen), second-generation antagonist (epinastine), or placebo. We also measured subjective sleepiness by visual analogue scale (VAS) test.


RESULTS
Cortical activation at the lateral prefrontal region increased during the performance of working memory and selective attention tasks in subjects receiving epinastine and placebo but not in those who took ketotifen. No significant difference was observed at the occipital region in the visual perception task among the three drug groups. VAS score and the behavioral performance during working memory and visual perception tasks indicated sedative effects of ketotifen consistent with the findings of previous studies.


CONCLUSIONS
Our results suggest that the neural response for working memory and selective attention task was impaired by the administration of ketotifen in comparison with that of epinastine and placebo. The sedative effect in the neural response was not observed after epinastine administration.
Tsujii
Takeo
T
Center for Integrated Research on the Mind, Keio University, Mita 3-1-7, Minato-ku, Tokyo 108-0073, Japan. tuji@flet.keio.ac.jp
Yamamoto
Eriko
E
Ohira
Takayuki
T
Saito
Nozomu
N
Watanabe
Shigeru
S
D000284:Administration, Oral; D000328:Adult; D044466:Asian People; D001288:Attention / Q000187:drug effects / Q000502:physiology; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology; D001519:Behavior / Q000187:drug effects* / Q000502:physiology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003984:Dibenzazepines / Q000008:administration & dosage / Q000494:pharmacology; D004007:Dichotic Listening Tests / Q000379:methods; D004311:Double-Blind Method; D005260:Female; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology; D007665:Ketotifen / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology; D010108:Oxyhemoglobins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared / Q000379:methods; D013997:Time Factors; D014796:Visual Perception / Q000187:drug effects / Q000502:physiology
D003984:Dibenzazepines; D039563:Histamine H1 Antagonists, Non-Sedating; D006993:Hypnotics and Sedatives; D007093:Imidazoles; D010108:Oxyhemoglobins; C053090:epinastine; D007665:Ketotifen