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HBK-15, a Multimodal Compound, Showed an Anxiolytic-Like Effect in Rats
Neurochemical Research ( IF 3.7 ) Pub Date : 2022-11-09 , DOI: 10.1007/s11064-022-03802-x
Klaudia Lustyk 1 , Kinga Sałaciak 1 , Magdalena Jakubczyk 1 , Magdalena Jastrzębska-Więsek 2 , Anna Partyka 2 , Anna Wesołowska 2 , Henryk Marona 3 , Karolina Pytka 1
Affiliation  

Anxiety is a common mental disorder, and its prevalence has lately increased because of the COVID-19 pandemic. Unfortunately, the available anxiolytics are often ineffective, and most possess addictive potential. Thus, searching for novel compounds is essential. In our previous studies, we selected a multimodal compound, HBK-15, which showed a fast antidepressant-like effect in animal models of depression. HBK-15 demonstrated a high affinity for serotonin 5-HT1A receptors and moderate for 5-HT7, dopamine D2, and α1-adrenoceptors. Based on the receptor profile and preliminary studies, we aimed to investigate the anxiolytic potential of HBK-15 using the conditioned-response rat model of anxiety, i.e., the Vogel drinking test. We performed hot plate and free-drinking tests to exclude false positive results in the Vogel test. Using radioligand binding studies, we also investigated the affinity of the compound for the selected biological targets, which play a role in anxiety. Our experiments revealed that HBK-15 showed an anxiolytic-like effect in rats (5 mg/kg) without influencing the pain threshold or the amount of water consumed in the free-drinking test. Furthermore, the tested compound did not show a significant affinity for the selected biological targets, which suggests that its anxiolytic-like mechanism of action could be connected with the interaction with other receptors. This study indicates that multimodal compounds with a receptor profile similar to HBK-15 could be an attractive therapeutic option for patients with a generalized anxiety disorder. However, more studies are required to determine the exact mechanism of action of HBK-15 and its safety profile.



中文翻译:

HBK-15 是一种多峰化合物,在大鼠中显示出抗焦虑样作用

焦虑是一种常见的精神障碍,最近由于 COVID-19 大流行,其患病率有所增加。不幸的是,可用的抗焦虑药通常无效,而且大多数都具有成瘾性。因此,寻找新的化合物是必不可少的。在我们之前的研究中,我们选择了一种多峰化合物 HBK-15,它在抑郁症动物模型中显示出快速的抗抑郁样作用。HBK-15 对血清素 5-HT 1A受体具有高亲和力,对 5-HT 7、多巴胺 D 2和 α 1具有中等亲和力-肾上腺素能受体。基于受体概况和初步研究,我们旨在使用焦虑的条件反应大鼠模型(即 Vogel 饮酒试验)研究 HBK-15 的抗焦虑潜力。我们进行了热板和自由饮用测试,以排除 Vogel 测试中的假阳性结果。使用放射性配体结合研究,我们还研究了该化合物对选定生物靶标的亲和力,这些靶标在焦虑中起作用。我们的实验表明,HBK-15 在大鼠 (5 mg/kg) 中表现出类似焦虑的作用,而不会影响痛阈或自由饮水试验中消耗的水量。此外,测试的化合物对选定的生物靶标没有显示出显着的亲和力,这表明其类似抗焦虑的作用机制可能与与其他受体的相互作用有关。这项研究表明,具有与 HBK-15 相似的受体谱的多峰化合物可能是广泛性焦虑症患者的一种有吸引力的治疗选择。然而,需要更多的研究来确定 HBK-15 的确切作用机制及其安全性。

更新日期:2022-11-10
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