Yaksh T L
J Pain Symptom Manage. 1992 Aug;7(6):356-61. doi: 10.1016/0885-3924(92)90089-z.
Systematic studies on the pharmacology of the antinociceptive activity of spinally administered agents have emphasized the action in animal models of mu and delta opioid receptors. Importantly, aside from receptor selectivity, the opioid agonists differ in the property of efficacy. Agents with high efficacy (large receptor reserves) show smaller rightward shifts in their dose-response curves in the face of a given degree of opioid tolerance or when the stimulus intensity is elevated. With regard to loss of drug effect with long-term exposure (tolerance), multiple mechanisms may be considered, including changes in stimulus intensity, change in afferent processing, or changes in receptor number/coupling. Basic studies are providing insights into these several mechanisms.
对脊髓给药制剂的抗伤害感受活性进行的系统药理学研究着重于μ和δ阿片受体在动物模型中的作用。重要的是，除了受体选择性外，阿片类激动剂在效能特性上也有所不同。具有高效能（大量受体储备）的药物在面对一定程度的阿片类耐受性或刺激强度升高时，其剂量反应曲线的右移较小。关于长期暴露导致药物效应丧失（耐受性），可以考虑多种机制，包括刺激强度的变化、传入处理的变化或受体数量/偶联的变化。基础研究正在为这些机制提供深入见解。
