Promising anticonvulsant and/or analgesic compounds among 5-chloro-2- or 5-chloro-4-methyl derivatives of xanthone coupled to aminoalkanol moieties-Design, synthesis and pharmacological evaluation.

A series of 10 aminoalkanol derivatives of 5-chloro-2- or 5-chloro-4-methylxanthone was synthetized and evaluated for anticonvulsant properties (MES test, mice, intraperitoneal) and compared with neurotoxicity rotarod test (NT, mice, i.p.). The best results both in terms of anticonvulsant activity and protective index value were obtained for 3: 5-chloro-2-([4-hydroxypiperidin-1-yl]methyl)-9H-xanthen-9-one hydrochloride. Compounds: 1-3, 7 and 10 revealed ED50 values in MES test: 42.78, 31.64, 25.76, 46.19 and 52.50 mg/kg b.w., respectively. 3 showed 70% and 72% of inhibition control specific binding of sigma-1 (σ1) and sigma-2 (σ2) receptor, respectively. 3 exhibited also antinociceptive activity at dose 2 mg/kg b.w. after chronic constriction injury in mice. 1, 3, 7 and 10 were evaluated on gastrointestinal flora and proved safe. In genotoxicity test (UMU-Chromotest) compounds 1, 7 and 10 proved safe at dose 150-300 µg/ml. The pharmacokinetic analysis showed rapid absorption of all studied molecules from the digestive tract (tmax  = 5-30 min). The bioavailability of the compounds ranged from 6.6% (1) to 16% (10). All studied compounds penetrate the blood-brain barrier with brain to plasma ratios varied from 4.15 (3) to 7.6 (compound 7), after i.v. administration, and from 1 (7) to 5.72 (3) after i.g. administration.

Variability of Pornographic Content Consumed and Longest Session of Pornography Use Associated With Treatment Seeking and Problematic Sexual Behavior Symptoms.

INTRODUCTION: Most of the previous studies on problematic pornography use and related behavior have focused on such descriptors of pornography use habits as frequency or time devoted to pornography use. AIM: We argue that this constitutes a narrow view and indicators that characterize other aspects of explicit content consumption, namely (i) longest session of pornography viewing (which may be related to binge behavior), as well as (ii) variability of consumed pornographic content, can also be useful indicators. METHODS: An online study based on a sample of 132 heterosexual men seeking treatment for problematic pornography use, referred by therapists after their initial visit and 437 non-treatment seekers in the control group. MAIN OUTCOME MEASURES: The main outcomes of this study are reported longest, non-stop session of viewing pornography, variability in consumed pornographic content (including paraphilic and violent pornography), actual treatment seeking for problematic pornography use and severity of symptoms, and average weekly time devoted to pornography use. RESULTS: Our analysis showed that longest session of viewing pornographic content as well as the variety of consumed pornography influenced the decision to seek treatment and the severity of symptoms even when the sheer amount of time devoted to pornography use was controlled. CONCLUSION: This is one of the few studies examining the role of engagement in prolonged sessions of pornography use and the variability of consumed pornographic content in the clinical context of problematic sexual behavior. The study's main limitations are its relatively narrow method of operationalization of variability of pornographic content and longest session of pornography viewing, as well as its cross-sectional, online, and anonymous character. As the described factors have an important influence on treatment seeking and the severity of experienced symptoms, they should be considered in the process of assessing compulsive sexual behavior disorder and related symptoms. Lewczuk K, Lesniak J, Lew-Starowicz M, et al. Variability of Pornographic Content Consumed and Longest Session of Pornography Use Associated With Treatment Seeking and Problematic Sexual Behavior Symptoms. Sex Med 2021;9:100276.