Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065.
Pharmacol Rev. 2013 Sep 27;65(4):1257-317. doi: 10.1124/pr.112.007138. Print 2013.
Opiates are among the oldest medications available to manage a number of medical problems. Although pain is the current focus, early use initially focused upon the treatment of dysentery. Opium contains high concentrations of both morphine and codeine, along with thebaine, which is used in the synthesis of a number of semisynthetic opioid analgesics. Thus, it is not surprising that new agents were initially based upon the morphine scaffold. The concept of multiple opioid receptors was first suggested almost 50 years ago (Martin, 1967), opening the possibility of new classes of drugs, but the morphine-like agents have remained the mainstay in the medical management of pain. Termed mu, our understanding of these morphine-like agents and their receptors has undergone an evolution in thinking over the past 35 years. Early pharmacological studies identified three major classes of receptors, helped by the discovery of endogenous opioid peptides and receptor subtypes-primarily through the synthesis of novel agents. These chemical biologic approaches were then eclipsed by the molecular biology revolution, which now reveals a complexity of the morphine-like agents and their receptors that had not been previously appreciated.
阿片类药物是可用于治疗多种医学问题的最古老药物之一。尽管目前的重点是疼痛，但早期的用途最初集中在治疗痢疾上。鸦片含有高浓度的吗啡和可待因，以及蒂巴因，蒂巴因用于合成多种半合成阿片类镇痛药。因此，最初基于吗啡骨架的新药物并不奇怪。50 年前，人们首次提出了多种阿片受体的概念（Martin，1967），为新药类的出现开辟了可能性，但类似吗啡的药物仍然是疼痛医学管理的主要药物。这些类似吗啡的药物及其受体被称为μ，在过去 35 年中，我们对它们的认识经历了思维上的演变。早期的药理学研究通过发现内源性阿片肽和受体亚型（主要是通过合成新型药物），帮助确定了三类主要受体。然后，这些化学生物学方法被分子生物学革命所取代，分子生物学革命现在揭示了类似吗啡的药物及其受体的复杂性，这是以前没有被认识到的。
