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首页> 外文期刊>Current Topics in Medicinal Chemistry >Editorial [Hot Topic: Adrenoceptors as Targets in Drug Discovery: Medicinal Chemistry and Therapeutical Potential (Guest Editors: Professors Maria Pigini and Wilma Quaglia)]
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Editorial [Hot Topic: Adrenoceptors as Targets in Drug Discovery: Medicinal Chemistry and Therapeutical Potential (Guest Editors: Professors Maria Pigini and Wilma Quaglia)]

机译：社论[热门话题：肾上腺素受体作为药物发现的靶标：药物化学和治疗潜力（来宾编辑：玛丽亚·皮吉尼教授和威尔玛·夸利亚教授）]

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Adrenoceptors continue to represent important and innovative pharmacological targets, even though their discovery dates back to more than 100 years ago: in fact, in 1905 Langley postulated that adrenaline exerted its action by interacting with “receptive substances” [Langley, J. N. J. Physiol. (London) 1905, 33, 374-413]; since then numerous studies have been carried out.nnThe first distinction between α and β receptors was postulated in 1948 by Ahlquist, who, however, in 1973 still had doubts on their effective existence, such a differentiation being defined “...an abstract concept conceived to explain observed responses of tissues produced by chemicals of various structure” [Ahlquist, R. P. Adrenergic Receptors: a Personal and Practical View. Perspect. Biol. Med. 1973, 17, 119-122].nnSince then, radioligand binding studies, second messenger assays and molecular biology techniques have led to the identification of nine different subtypes, which, however, do not seem to explain fully all the experimental observations. Even if it is difficult to postulate the existence of other members of this superfamily (however, at the same time most attention has been devoted to two possible candidates, the α1L and β4), the improvement in the selectivity of interaction and, therefore, in the quality of response is explained through the recognition of different affinity states or non-canonical receptor sites.nnIn this issue, after a review of the subclassification of the α- and β-adrenoceptors by Hieble, the recent advances in the discovery of α1-agonists and antagonists are highlighted by Bishop and Melchiorre et al., respectively. Agonists and antagonists directed to α2-adrenoceptors and their clinical utility are described by Giannella et al. and Crassous et al., respectively. Carrieri and Fano examine the methodological approaches and structural features of the 3D models in α- adrenoceptor characterization, and Hieble gives an overview of β-adrenoceptor ligands and their therapeutic uses. Finally, Schaak et al. focus on possible genetic variations of human adrenoceptors.nnThe therapeutic applications of adrenergic ligands are various: for example, the primary indications of the α 1-agonists are in nasal congestion, otitis and in stress urinary incontinence; agonists, acting at the α2-adrenoceptors, are extremely valuable adjuncts to anesthetics and analgesics; those at the β2-adrenoceptors are used as bronchodilators, whereas β3-agonists prove to be efficacious in the treatment of overactive bladder. The use of the β1/β2-antagonists as antihypertensives, α1-antagonists in the treatment of benign prostatic hyperplasia, and α2-antagonists in attention deficit hyperactivity disorder is well established.nnA better knowledge of the structural differences of the various receptor species, in particular within each of the three distinct classes, and of the possible aggregation of such proteins in homo- and heterodimer forms will help to design new ligands that, being more selective, will have new and safer therapeutic uses.
机译：尽管肾上腺素能受体的发现可以追溯到100多年前，但它们仍然代表着重要的和创新的药理学靶标：事实上，Langley于1905年提出肾上腺素通过与“受体物质”相互作用来发挥其作用[Langley，J. N. J. Physiol。Chem。 （伦敦）1905，33，374-413]；此后进行了大量研究。nn受体的首次区分是由阿奎斯特（Ahlquist）于1948年提出的，但是在1973年，阿尔法斯特仍然对它们的有效存在存有疑问，这种区别被定义为“ ...一个抽象概念旨在解释观察到的由各种结构的化学物质产生的组织的反应” [Ahlquist，RP肾上腺素能受体：个人和实践的观点。透视。生物学中1973，17，119-122] .nn从那时起，放射性配体结合研究，第二信使测定和分子生物学技术已导致鉴定出9种不同的亚型，但是，这些亚型似乎并不能完全解释所有的实验观察结果。即使很难假设存在该超家族的其他成员（但是，同时大多数注意力都集中在两个可能的候选对象α1L和β4上），相互作用的选择性也因此得到改善。通过识别不同的亲和力状态或非规范受体位点来解释反应的质量。nn在本期中，在对Hieble对α-和β-肾上腺素能受体的亚分类进行综述后，发现了α1-激动剂和拮抗剂分别由Bishop和Melchiorre等人强调。 Giannella等人描述了针对α2-肾上腺素受体的激动剂和拮抗剂及其临床应用。和Crassous等人。 Carrieri和Fano检查了3D模型在α-肾上腺素受体表征中的方法论方法和结构特征，Hieble概述了β-肾上腺素受体配体及其治疗用途。最后，Schaak等。肾上腺素能配体的治疗应用是多种多样的：例如，α1-激动剂的主要适应症是鼻充血，中耳炎和压力性尿失禁。作用于α2-肾上腺素受体的激动剂是麻醉药和镇痛药的极有价值的辅助剂； β2-肾上腺素能受体的那些被用作支气管扩张剂，而β3-激动剂被证明在膀胱过度活动症的治疗中是有效的。众所周知，已经将β1/β2拮抗剂用作降压药，α1拮抗剂用于治疗良性前列腺增生以及α2拮抗剂在注意力缺陷多动障碍中的应用。特别是在三个不同类别中的每个类别中，此类蛋白质可能以同二聚体和异二聚体形式聚集，将有助于设计新的配体，这些配体更具选择性，将具有新的和更安全的治疗用途。

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