Pergolizzi Joseph, Magnusson Peter, Coluzzi Flaminia, Breve Frank, LeQuang Jo Ann K, Varrassi Giustino
Cardiology, Native Cardio Inc., Naples, USA.
Cardiology, Center of Research and Development Region Gävleborg/Uppsala University, Gävle, SWE.
Cureus. 2022 Jun 16;14(6):e26000. doi: 10.7759/cureus.26000. eCollection 2022 Jun.
Atypical opioids such as tramadol, tapentadol, and cebranopadol combine two complementary mechanisms of action into a single molecule, creating novel analgesic agents. These are synthetic small molecules: cebranopadol is not yet market released; tramadol and tapentadol are commercially available and have immediate-release (IR) and extended-release (ER) formulations. Tramadol has been widely used in the United States in recent years and works as a prodrug in that its metabolites are active in inhibiting serotonin and norepinephrine reuptake. Tapentadol is a direct-acting agent with a faster onset of action and is a mu-opioid-receptor agonist and also inhibits noradrenaline reuptake. Cebranopadol is the newest of these drugs, a first-in-class atypical analgesic that combines mu-opioid receptor (MOR) agonism with activity at the nociception/orphanin (NOP) FQ petide receptors. Cebranopadol may be considered a partial kappa-opioid receptor agonist as well. The pharmacology of these unique single-entity agents allows them to offer analgesic benefit with fewer side effects and risks. Clinical studies have demonstrated the safety and efficacy of tramadol and tapentadol, and promising but limited studies for cebranopadol show good analgesic effect and safety. Serotonin toxicity or 'serotonin syndrome' may occur with accumulation of serotonin with tramadol. While the misuse of these agents is limited in the United States, tramadol misuse is prevalent in Iran and parts of Africa. Patients have been successfully rotated from one of these agents to another. All three agents show promise in the treatment of cancer and non-cancer pain and their unique formulation in a single molecule reduces the pill burden.
曲马多、他喷他多和塞布诺帕多等非典型阿片类药物将两种互补的作用机制结合在一个分子中，从而产生了新型镇痛药。这些都是合成小分子：塞布诺帕多尚未上市；曲马多和他喷他多已上市，有速释（IR）和缓释（ER）剂型。近年来，曲马多在美国已被广泛使用，它作为一种前体药物，其代谢产物在抑制5-羟色胺和去甲肾上腺素再摄取方面具有活性。他喷他多是一种直接作用药物，起效更快，是μ-阿片受体激动剂，还能抑制去甲肾上腺素再摄取。塞布诺帕多是这些药物中最新的一种，是一流的非典型镇痛药，它将μ-阿片受体（MOR）激动作用与伤害感受/孤啡肽（NOP）FQ肽受体活性相结合。塞布诺帕多也可被视为部分κ-阿片受体激动剂。这些独特的单一实体药物的药理学特性使其能够在副作用和风险较少的情况下提供镇痛益处。临床研究已证明曲马多和他喷他多的安全性和有效性，而针对塞布诺帕多的有前景但有限的研究显示出良好的镇痛效果和安全性。曲马多导致5-羟色胺蓄积时可能会发生5-羟色胺毒性或“5-羟色胺综合征”。虽然这些药物在美国的滥用情况有限，但曲马多滥用在伊朗和非洲部分地区很普遍。患者已成功地从其中一种药物转换为另一种药物。所有这三种药物在治疗癌症和非癌症疼痛方面都显示出前景，并且它们在单个分子中的独特剂型减轻了服药负担。
