Partyka Anna, Wasik Anna, Jastrzębska-Więsek Magdalena, Mierzejewski Paweł, Bieńkowski Przemysław, Kołaczkowski Marcin, Wesołowska Anna
Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Cracow, Poland.
Department of Pharmacology, Institute of Psychiatry and Neurology, 9 Sobieskiego Street, 02-957, Warsaw, Poland.
Naunyn Schmiedebergs Arch Pharmacol. 2016 Jun;389(6):593-602. doi: 10.1007/s00210-016-1229-3. Epub 2016 Mar 16.
Behavioral and psychological symptoms of dementia (BPSD) include apathy, sleep problems, irritability, wandering, elation, agitation/aggression, and mood disorders such as depression and/or anxiety. Elderly patients are usually treated with second-generation antipsychotics; however, they present not enough efficacy against all symptoms observed. Hence, there still is an unmet need for novel pharmacotherapeutic agents targeted BPSD. A novel arylsulfonamide derivative ADN-1184 has been developed that possesses a preclinical profile of activity corresponding to criteria required for treatment of both psychosis and depressive symptoms of BPSD without exacerbating cognitive impairment or inducing motor disturbances. To broaden its pharmacological efficacy toward anxiety symptoms, its anxiolytic properties have been examined in common animal preclinical models in rats and mice. ADN-1184 significantly increased the number of entries into open arms measured in the elevated plus-maze test; however, it simultaneously increased parameters of exploratory activity. In the Vogel conflict drinking test, ADN-1184 dose-dependently and significantly increased the number of shocks accepted and the number of licks. Moreover, in mice, it also had specific anxiolytic-like activity in the four-plate test, and only negligible one at a specific mid-range dose measured in the spontaneous marble burying test. The obtained findings reveal that ADN-1184 displays anxiolytic-like activity in animal models of anxiety which employed punished stimuli. In its unusual combination of some anxiolytic action with already proven antipsychotic and antidepressant properties, and lack of any disruptive impact on learning and memory processes and motor coordination, ADN-1184 displays a profile that would be desired for a novel therapeutic for BPSD.
痴呆的行为和心理症状（BPSD）包括冷漠、睡眠问题、易怒、徘徊、欣快、激动/攻击行为以及抑郁和/或焦虑等情绪障碍。老年患者通常使用第二代抗精神病药物进行治疗；然而，这些药物对所观察到的所有症状的疗效并不充分。因此，针对BPSD的新型药物治疗剂仍存在未满足的需求。一种新型芳基磺酰胺衍生物ADN - 1184已被开发出来，其临床前活性特征符合治疗BPSD的精神病和抑郁症状所需的标准，且不会加重认知障碍或引起运动障碍。为了扩大其对焦虑症状的药理作用，已在大鼠和小鼠的常见动物临床前模型中研究了其抗焦虑特性。ADN - 1184在高架十字迷宫试验中显著增加了进入开放臂的次数；然而，它同时增加了探索活动的参数。在Vogel冲突饮水试验中，ADN - 1184剂量依赖性地显著增加了接受电击的次数和舔舐次数。此外，在小鼠中，它在四板试验中也具有特定的抗焦虑样活性，而在自发大理石埋藏试验中，在特定的中剂量下仅有可忽略不计的活性。所获得的研究结果表明，ADN - 1184在采用惩罚性刺激的焦虑动物模型中表现出抗焦虑样活性。ADN - 1184具有一些抗焦虑作用与已证实的抗精神病和抗抑郁特性的不寻常组合，并且对学习和记忆过程以及运动协调没有任何干扰作用，显示出一种新型BPSD治疗药物所期望的特征。
