van Diepen Hester, Schlicker Eberhard, Michel Martin C
Department of Pharmacology & Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Naunyn Schmiedebergs Arch Pharmacol. 2008 Oct;378(4):345-69. doi: 10.1007/s00210-008-0327-2. Epub 2008 Jul 25.
Rimonabant is an inverse agonist specific for cannabinoid receptors and selective for their cannabinoid-1 (CB(1)) subtype. Although CB(1) receptors are more abundant in the central nervous system, rimonabant has many effects in the periphery, most of which are related to prejunctional modulation of transmitter release from autonomic nerves. However, CB(1) receptors are also expressed in, e.g., adipocytes and endothelial cells. Rimonabant inhibits numerous cardiovascular cannabinoid effects, including the decrease of blood pressure by central and peripheral (cardiac and vascular) sites of action, with the latter often being endothelium dependent. Rimonabant may also antagonize cannabinoid effects in myocardial infarction and in hypotension associated with septic shock or liver cirrhosis. In the gastrointestinal tract, rimonabant counteracts the cannabinoid-induced inhibition of secretion and motility. Although not affecting most cannabinoid effects in the airways, rimonabant counteracts inhibition of smooth-muscle contraction by cannabinoids in urogenital tissues and may interfere with embryo attachment and outgrowth of blastocysts. It inhibits cannabinoid-induced decreases of intraocular pressure. Rimonabant can inhibit proliferation of, maturation of, and energy storage by adipocytes. Among the many cannabinoid effects on hormone secretion, only some are rimonabant sensitive. The effects of rimonabant on the immune system are not fully clear, and it may inhibit or stimulate proliferation in several types of cancer. We conclude that direct effects of rimonabant on adipocytes may contribute to its clinical role in treating obesity. Other peripheral effects, many of which occur prejunctionally, may also contribute to its overall clinical profile and lead to additional indications as well adverse events.
利莫那班是一种对大麻素受体具有特异性且对其大麻素-1（CB(1)）亚型具有选择性的反向激动剂。尽管CB(1)受体在中枢神经系统中更为丰富，但利莫那班在外周也有许多作用，其中大多数与自主神经递质释放的节前调节有关。然而，CB(1)受体也表达于例如脂肪细胞和内皮细胞中。利莫那班抑制多种心血管大麻素效应，包括通过中枢和外周（心脏和血管）作用部位降低血压，后者通常依赖于内皮。利莫那班还可能拮抗心肌梗死以及与脓毒性休克或肝硬化相关的低血压中的大麻素效应。在胃肠道中，利莫那班可抵消大麻素诱导的分泌和运动抑制。尽管利莫那班不影响气道中的大多数大麻素效应，但它可抵消泌尿生殖组织中大麻素对平滑肌收缩的抑制作用，并可能干扰胚泡的着床和生长。它抑制大麻素诱导的眼压降低。利莫那班可抑制脂肪细胞的增殖、成熟和能量储存。在大麻素对激素分泌的众多作用中，只有一些对利莫那班敏感。利莫那班对免疫系统的作用尚不完全清楚，它可能抑制或刺激几种类型癌症的增殖。我们得出结论，利莫那班对脂肪细胞的直接作用可能有助于其在治疗肥胖症中的临床作用。其他外周作用，其中许多发生在节前，也可能有助于其整体临床特征，并导致其他适应症以及不良事件。
