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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Behavioural satiety sequence (BSS): separating wheat from chaff in the behavioural pharmacology of appetite.
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Behavioural satiety sequence (BSS): separating wheat from chaff in the behavioural pharmacology of appetite.

机译：行为饱腹感序列（BSS）：在食欲的行为药理学上将小麦与谷壳分离。

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The history of anti-obesity drug development is far from glorious, with transient magic bullets and only a handful of agents currently licensed for clinical use. In view of recent progress in our understanding of the multiplicity of signalling pathways involved in appetite regulation, and the resultant deluge of reports on the anorectic efficacy of novel therapies, it seems timely to stress the need to differentiate treatments that suppress intake by primary means from those that only indirectly achieve this endpoint. The current article reviews the conceptual history of the behavioural satiety sequence (BSS), also known as the behavioural sequence of satiety, post-ingestive satiety, and the postprandial satiety sequence. Early research confirmed that natural satiation, produced by a caloric load on the gut, is associated with a predictable transition from feeding through grooming to resting. Although many less naturalistic manipulations are also capable of reducing food intake, very few do so without disrupting the normal structure of this feeding cycle. Thus, while CCK and d-fenfluramine reduce intake by accelerating but otherwise maintaining the integrity of the BSS, other anorectic interventions disrupt the BSS through response competition (e.g. d-amphetamine), nausea/discomfort (e.g. lithium chloride) and/or interference with taste-mediated positive feedback (e.g. quinine adulteration of the diet). A substantial literature now strongly supports the specific involvement of serotonin 5-HT(1B) and 5-HT(2C) receptor subtypes in satiety and in the anorectic effect of agents such as fenfluramine and fluoxetine. Recent BSS analyses have also identified rather selective anorectic profiles for the dual noradrenaline and 5-HT reuptake inhibitor sibutramine, the orexin-1 receptor antagonist SB-334867, and the broad spectrum opioid receptor antagonist naloxone. However, similar analyses have offered littleo support for the anorectic potential of the gut peptide PYY(3-36) while the acute anorectic efficacy of cannabinoid CB1 receptor antagonist/inverse agonists appears largely to be secondary to response competition. In contrast, studies with low-dose combinations of naloxone and CB1 receptor antagonist/inverse agonists have very recently confirmed the potential of drug polytherapies not only in appetite suppression but also in attenuating/eliminating unwanted side-effects. In sum, as BSS analysis offers a reliable means of differentiating the wheat (primary anorectics) from the chaff (secondary anorectics), it should form an integral part of early phase testing in any anti-obesity drug screening programme.
机译：抗肥胖药的发展历史远非光荣，它具有短暂的魔力子弹，目前只有少数药物可用于临床。鉴于最近我们对食欲调节所涉及的信号传导途径的理解有了新的进展，并且随之而来的是有关新疗法的厌食功效的报告的大量涌现，似乎有必要强调指出，有必要区分以抑制主要摄入量的治疗方法那些仅间接达到此终点的产品。当前文章回顾了行为饱腹感序列（BSS）的概念历史，也称为饱腹感行为序列，厌食后饱足感和餐后饱足感序列。早期的研究证实，肠道热量负荷产生的自然饱足与从进食到梳理到休息的可预测过渡有关。尽管许多不那么自然的操作也能够减少食物摄入，但是很少这样做不会破坏该进食周期的正常结构。因此，虽然CCK和d-芬氟拉明通过加速而又保持了BSS的完整性来降低摄入量，但其他厌食干预措施通过反应竞争（例如d-苯异丙胺），恶心/不适（例如氯化锂）和/或干扰来破坏BSS。口味介导的积极反馈（例如饮食中奎宁掺假）。现在，大量文献强烈支持5-羟色胺5-HT（1B）和5-HT（2C）受体亚型在饱腹感和诸如芬氟拉明和氟西汀等药物的厌食作用中的特定参与。最近的BSS分析还确定了去甲肾上腺素和5-HT再摄取抑制剂西布曲明，orexin-1受体拮抗剂SB-334867和广谱阿片受体拮抗剂纳洛酮的选择性厌食特性。但是，类似的分析几乎没有/没有支持肠道肽PYY（3-36）的厌食潜力，而大麻素CB1受体拮抗剂/反向激动剂的急性厌食功效似乎在响应竞争中居于次要地位。相比之下，纳洛酮和CB1受体拮抗剂/反向激动剂的低剂量组合研究最近已经证实，药物多疗法的潜力不仅可以抑制食欲，而且可以减轻/消除不良副作用。总而言之，由于BSS分析提供了一种区分小麦（主要厌食药）和谷壳（次要厌食药）的可靠方法，因此它应该成为任何抗肥胖症药物筛选计划早期测试的组成部分。

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