Martin W R
Ann Emerg Med. 1986 Sep;15(9):1026-9. doi: 10.1016/s0196-0644(86)80123-8.
Analgesics such as morphine are toxic drugs that kill by producing respiratory depression. Further morphine-like drugs produce a high level of physical dependence and are highly reinforcing in some subjects. A systematic search, conducted over the last 50 years, for safer and less addicting analgesic has revealed that opioid analgesics act on different types of opioid receptors (mu, kappa, and sigma), and that they may function as mixed agonist-antagonists or as partial agonists. Thus some mixed agonists function as competitive antagonists at the mu receptor and as partial or strong agonists at the kappa or sigma receptor. When mixed agonists produce the same pharmacologic effects (eg, analgesia) by acting on different receptors, they invoke the principle of receptor dualisms. Drugs that produce agonist (analgesic) effects by acting on the kappa receptors are an order of magnitude safer than the mu agonists and produce a lesser degree of physical dependence than strong mu agonists. Thus safer, less addicting analgesics have been produced that act either as agonist-antagonists or by being partial agonists.
吗啡等镇痛药是毒性药物，可通过产生呼吸抑制来致人死亡。其他类吗啡药物会导致高度的身体依赖性，并且在某些人身上具有很强的成瘾性。在过去50年里，为寻找更安全、成瘾性更低的镇痛药而进行的系统研究表明，阿片类镇痛药作用于不同类型的阿片受体（μ、κ和σ），它们可能作为混合激动剂-拮抗剂或部分激动剂发挥作用。因此，一些混合激动剂在μ受体上作为竞争性拮抗剂，在κ或σ受体上作为部分激动剂或强效激动剂发挥作用。当混合激动剂通过作用于不同受体产生相同的药理作用（如镇痛）时，它们遵循受体二元论原则。通过作用于κ受体产生激动剂（镇痛）作用的药物比μ激动剂安全一个数量级，并且与强效μ激动剂相比，产生的身体依赖性程度更低。因此，已经生产出了更安全、成瘾性更低的镇痛药，它们要么作为激动剂-拮抗剂发挥作用，要么作为部分激动剂发挥作用。
