Parası kalmadığı için otobüse binemiyordur ailesi porno izle ona daha yeni para gönderdiği için tekrar porno istemeye utanınca mecburen otostop çekmek için youporn çantasını alarak yol kenarına gelir etekli porno liseli türk kız yol kenarında dururken yanına yaklaşan porno kibar bir gencin onu gideceği yere kadar bırakmak porno izle istemesine çok mutlu olur arabaya bindiklerinde gideceği yer ile porno arabayı kullanan adamın gittiği yer arasında çok mesafe sex izle farkı olduğunu anlayan türk kız bu yaptığı porno indir iyilik karşısında arabada ona memelerini açar porno sapıklaşan adam yol kenarındaki hotelde durarak porno izle üniversiteli otostop çeken türk kızına odada sakso çektirip sikerCompounds with dual activity: Serotonin transporter inhibitor (SERT) and serotonin 5-HT2C receptor antagonist properties for the treatment of depression| Abstract

Abstract

Compounds with dual activity: Serotonin transporter inhibitor (SERT) and serotonin 5-HT2C receptor antagonist properties for the treatment of depression

Author(s): Hedvig Blcskei

 Depression is a common mental disease, which affects 6-7% of the population. Major depressive disorder is treated by talk therapy or medication, usually by antidepressants which are either serotonin selective reuptake inhibitors (SSRI) like fluoxetine and paroxetine, or by serotonin and norepinephrine reuptake inhibitors (SNRI) like duloxetine and venlafaxine. Because of the well-known slow onset and side effects of the antidepressants, there is an unmet medical need for further efficient drugs with more advantageous side effect profiles. Some antidepressants, (e.g. trazodone, nefazodone, mianserin, mirtazapine) act both as SERT inhibitors and 5-HT2C antagonists. The suggestion arose that the compounds with dual activities might be advantageous. The design and synthesis of dually active compounds are more difficult processes than the design and synthesis of selective inhibitors. Éliás and coworkers developed various types of hybrid compounds with serotonin transporter inhibitor (SERT) and serotonin 5-HT2C receptor antagonist activities [O.Éliás et al. Bioorg. Med. Chem. Lett.24, 2118 (2014), ibid 26, 914 (2016)].

We have synthesized a compound family with substituted phenoxy-benzylamine moieties. Our novel compounds showed excellent rSERT Ki and r5-HT2C Ki values and advantageous physico-chemical properties (clogP, solubility). A few structure-activity relationships (SAR) have also been established.


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