%0 Journal Article %T Preclinical characterization of AMPA receptor potentiator TAK©\137 as a therapeutic drug for schizophrenia %A Akiyoshi Kunugi %A Atsushi Suzuki %A Haruhide Kimura %A Maiko Tanaka %A Motohisa Suzuki %A Noriko Suzuki %J Archive of "Pharmacology Research & Perspectives". %D 2019 %R 10.1002/prp2.479 %X The downregulation of the glutamate system may be involved in positive, negative, and cognitive symptoms of schizophrenia. Through enhanced glutamate signaling, the activation of the ¦Á©\amino©\3©\hydroxy©\5©\methyl©\4©\isoxazole©\propionic acid (AMPA) receptor, an ionotropic glutamate receptor, could be a new therapeutic strategy for schizophrenia. TAK©\137 is a novel AMPA receptor potentiator with minimal agonistic activity; in this study, we used rodents and nonhuman primates to assess its potential as a drug for schizophrenia. At 10 mg kg£¿1 p.o., TAK©\137 partially inhibited methamphetamine©\induced hyperlocomotion in rats, and at 3, 10, and 30 mg kg£¿1 p.o., TAK©\137 partially inhibited MK©\801©\induced hyperlocomotion in mice, suggesting weak effects on the positive symptoms of schizophrenia. At 0.1 and 0.3 mg kg£¿1 p.o., TAK©\137 significantly ameliorated MK©\801©\induced deficits in the social interaction of rats, demonstrating potential improvement of impaired social functioning, which is a negative symptom of schizophrenia. The effects of TAK©\137 were evaluated on multiple cognitive domains¡ªattention, working memory, and cognitive flexibility. TAK©\137 enhanced attention in the five©\choice serial reaction time task in rats at 0.2 mg kg£¿1 p.o., and improved working memory both in rats and monkeys: 0.2 and 0.6 mg kg£¿1 p.o. ameliorated MK©\801©\induced deficits in the radial arm maze test in rats, and 0.1 mg kg£¿1 p.o. improved the performance of ketamine©\treated monkeys in the delayed matching©\to©\sample task. At 0.1 and 1 mg kg£¿1 p.o., TAK©\137 improved the cognitive flexibility of subchronic phencyclidine©\treated rats in the reversal learning test. Thus, TAK©\137©\type AMPA receptor potentiators with low intrinsic activity may offer new therapies for schizophrenia %K AMPA %K AMPA receptor potentiator %K schizophrenia %U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507438/