NARCOTIC TOLERANCE AND PHYSICAL DEPENDENCE MECHANISMS

阿片类药物耐受和身体依赖的机制 开发情况正在调查中。已经提出了一种假设 基于阿片剂与钙离子相互作用的阿片类药物作用。急性阿片类药物 这种影响归因于神经元钙离子的降低，从而导致 神经元活性受抑制的原因是脑细胞数量减少 神经递质释放。容忍是由反适应产生的 神经细胞钙离子降低的反应及其结果是钙离子 对抗鸦片类药物作用的蓄积(耐受性)。有能力 在频繁重复服用阿片类药物依赖后保留钙离子 论鸦片类药物(身体依赖)的存在和停用 阿片类药物导致胞浆钙离子和神经递质释放增加 还有戒断综合症。为了验证这一假设，对急性胰腺炎的研究 以及长期服用阿片类药物对钙离子通量的影响 小鼠和大鼠的突触体、肥大细胞和红细胞。 药理学研究也正在对分离的组织或 器官制剂，如豚鼠回肠和输精管 小鼠、大鼠和兔子来定义Mu、kappa和Delta的重要性 耐受性和依赖性中的受体。

The mechanisms involved in opiate tolerance and physical dependence development are under investigation. A hypothesis has been proposed for opiate action that is based on opiate-Ca++ interactions. Acute opiates effects are attributed to a lowering of neuronal Ca++ with consequent inhibition of neuronal activity resulting from a decrease in neurotransmitter release. Tolerance results from a counteradaptive response on the lowering of neuronal Ca++ and the consequence is Ca++ accumulation which antagonizes opiate effects (tolerance). The ability to retain Ca++ after frequent repeated opiate administration becomes dependent on the presence of the opiate (physical dependence) and discontinuance of the opiate results in increased cytosol Ca++ and neurotransmitter release and the withdrawal syndrome. To validate the hypothesis, studies on acute and chronic opiate administration on calcium flux are being carried out on synaptosomes, mast cells and red blood cells of the mouse and rat. Pharmacologic studies are also being performed on the isolated tissue or organ preparations such as the guinea pig ileum and the vas deferens of the mouse, rat and rabbit to define the importance of mu, kappa and delta receptors in tolerance and dependence.