PHARMACOLOGY OF OPIOID RECEPTOR SUBTYPES

阿片剂和阿片肽通过结合特定的识别位点发挥作用， 或感受器。一些不同的阿片受体亚型已经被 确定了哪些药物具有不同的药理作用。近期 现在有证据表明，这些受体亚型中至少有五种可以 相互独立地中介止痛。此外，他们还在 神经轴的不同区域：冈上的MU1和kappa3以及MU2， 卡帕、L和三角洲呈棘状分布。脊柱/脊柱上的重要性 吗啡镇痛中的相互作用早已为人所知。我们建议 将这些研究扩展到脊柱/脊柱上的相互作用 各式各样的子类型。微注射研究也发现了重要的 大脑中吗啡可以缓解疼痛的区域。我们 建议研究这些选择性部位与脊髓的相互作用 机制也是如此。使用这种微注射方法，我们现在有了 观察到蓝斑之间的协同镇痛相互作用 中脑导水管周围的灰色。同时给药部分 这两个区域的激动剂都能产生不能产生的止痛。 在单一区域注射，而不考虑药物的剂量。我们计划 继续描述这些棘上/棘上的相互作用。 这一微量注射模型使我们能够检查 阿片类药物在亩L受体中的作用。我们还建议研究这些因素的作用 阿片受体在其他阿片类药物作用中的不同亚型， 尤其是呼吸抑制和胃肠抑制 中转。最后，我们希望研究非阿片类药物之间的相互作用。 阿片类药物的止痛和其他作用。抗抑郁药与CCK 拮抗剂已经被用来加强阿片类药物的镇痛作用，我们计划 检查这些相互作用，特别强调阿片类药物 涉及受体亚型系统。

Opiates and opioid peptides act by binding to specific recognition sites, or receptors. A number of different opioid receptor subtypes have been identified which mediate distinct pharmacological actions. Recent evidence now indicates that at least five of these receptor subtypes can mediate analgesia independently of each other. Furthermore, they act in different regions of the neuroaxis: mu1 and kappa3 supraspinally and mu2, kappa l and delta spinally. The importance of spinal/supraspinal interactions in morphine analgesia have long been known. We propose to extend these studies to the spinal/supraspinal interactions of the various subtypes. Microinjection studies also have identified important regions within the brain where morphine can elicit pain relief. We propose to examine the interactions of these selective sites with spinal mechanisms as well. Using this microinjection approach we now have observed synergistic analgesic interactions between the locus coerulus and the periaqueductal gray. Simultaneous administration of a partial agonist to both regions elicits analgesia which cannot be produced by injections to a single region regardless of the dose of drug. We plan to continue to characterize these supraspinal/supraspinal interactions. This microinjection model enables us to examine the intrinsic activity of opioids at mu l receptors. We also propose to study the roles of these various subtypes of opiate receptors in other opioid actions, particularly respiratory depression and inhibition of gastrointestinal transit. Finally, we hope to examine the interactions of nonopioid drugs upon opioid analgesia and other actions. Antidepressants and CCK antagonists have been used to potentiate opioid analgesia and we plan to examine these interactions with particular emphasis upon the opioid receptor subtype systems involved.