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Behavioural pharmacology

WS0701: a novel sedative-hypnotic agent acting on the adenosine system.


PMID 25171078

Abstract

To characterize the sedative and hypnotic profile of the novel adenosine derivative ((3S,4R,5R)-3,4-dihydroxy-5-(6-((4-hydroxy-3-methoxybenzyl)amino)-9H-purin-9-yl)tetrahydrofuran-2-yl) methyl diaconate (WS0701), we performed a variety of behavioural tests and investigated the influence of WS0701 on various sleep stages. In mice, WS0701 significantly increased the number of entries and time spent in open arms in the elevated plus maze test, indicating an anxiolytic effect. WS0701 decreased locomotor activity counts and head dips in the hole-board test and enhanced sodium pentobarbital-induced hypnosis. However, WS0701 did not induce the loss of the righting reflex or amnesic effects in behavioural models. In rats, WS0701 exerted a sedative effect and markedly prolonged the time spent in non-rapid-eye-movement sleep, especially slow-wave sleep, but reduced the time spent in rapid-eye-movement sleep (REMS). Pretreatment with the selective adenosine A2a receptor antagonist SCH58261 attenuated the sedative and hypnotic effects of WS0701. WS0701 did not protect mice against picrotoxin-induced seizures, but inhibited adenosine deaminase activity and increased adenosine levels in the frontal cortex and hypothalamus of mice. In conclusion, WS0701 shows anxiolytic, sedative as well as sleep stage alterative effects, which may be related to the adenosine system.