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Background: The purpose of this study was to characterize the novel sedative/hypnotic agent HSK3486, a 2,6-disubstituted alkylphenol analogue.Methods: The mechanism of action of HSK3486 was studied in competitive binding assays and whole-cell patch clamp assays. HSK3486 was administered by bolus intravenous injection to dogs and rats, and the loss of righting reflex as well as effects on the cardiovascular and respiratory systems were assessed. The in vitro metabolism of HSK3486 was analyzed by CYP450 genotyping and enzyme inhibition.Results: HSK3486 competed with t-butylbicycloorthobenzoate (TBOB) and t-butylbicyclophosphorothionate (TBPS) for binding to the gamma-aminobutyric acid type A (GABAA) receptor. HSK3486 potentiated GABA-evoked chloride currents at lower concentrations while activating GABAA receptor at higher concentrations. HSK3486 induced hypnosis in rats and dogs, and had a higher therapeutic index than propofol in rats. The hypnotic potency of HSK3486 was approximately 4-5 fold higher than that of propofol. HSK3486 exerted minimal effects on the cardiovascular system.Conclusions: HSK3486 is a positive allosteric regulator and direct agonist of GABAA receptor. It has a promising sedative/hypnotic effect and good in vivo pharmacokinetic properties, which justify further studies towards its clinical application.

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This exploratory study focused on Chinese social network sites (SNS) users to determine whether their online self-disclosure differed from offline and whether culture had an impact on the patterns of their self-disclosure. Sixteen active users of Chinese online social networks were interviewed about their self-disclosing experiences. Results of a qualitative analysis suggest that culture was likely to impact the behavior of study participants by modifying the patterns of self-disclosure. Participants tended to disclose themselves indirectly on SNS, strived to make positive impressions, and revealed few intimate issues. In face-to-face communication, the relationships between disclosers and target persons as well as the target persons' status and background influenced the contents of self-disclosure.