NIMODIPINE IN LITHIUM-REFRACTORY BIPOLAR PATIENTS

尼莫地平治疗锂难治性双相情感障碍患者

• 批准号: 3781501
• 负责人: R M POST
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3781501
• 关键词: anticonvulsants; antidepressants; bipolar depression; bipolar depression depressed phase; bipolar depression manic phase; calcium channel; calcium channel blockers; calcium metabolism; carbamazepine; clinical trials; combination chemotherapy; drug administration rate /duration; human subject; human therapy evaluation; mental disorder chemotherapy; psychopharmacology; relapse /recurrence; verapamil

Utilization of the calcium channel blocker nimodipine in affective disorders is based on several empirical and theoretical rationales. The L-type calcium channel blocker verapamil has been reported effective in the treatment of acute mania but not depression, and nimodipine has a different profile of effects compared with verapamil. It is more lipid soluble and blocks cocaine-induced hyperactivity and dopamine overflow and is also a better anticonvulsant in several model systems. Positive response to nimodipine has been observed in one of five patients with rapid but not ultradian cycling disorder and this was confirmed in an on- off-on (B-A-B) design. Three patients with ultra-ultra rapid cycling (ultradian cycling) showed complete or partial responses to the double- blind administration of nimodipine. The partial responder was confirmed in the B-A-B design and a more complete response was achieved with the addition of carbamazepine. Since carbamazepine has recently been described to inhibit calcium influx through the NMDA receptor in cerebellar granule cells, these data raise the possibility that drugs with differential effects on calcium channels may be useful in refractory patients. One patient with recurrent brief depression responded dramatically to the blind institution of nimodipine, relapsed on placebo substitution, and re-responded with reinstitution of active drug (B-A-B- A); this patient continued to show improvement when verapamil was substituted for nimodipine. These data suggest the utility of further exploring the clinical profile of nimodipine in refractor affective disorders and of the potential of altered calcium metabolism in this illness.

在情感中利用钙通道阻滞剂nimodipine 疾病基于几种经验和理论理由。 这 据报道，L型钙通道阻滞剂Verapamil有效 急性躁狂症的治疗但不抑郁，氮氨胺具有 与维拉帕米相比，效果的不同。 它更多的脂质 可溶并阻止可卡因诱导的多动症和多巴胺溢出 在几种模型系统中也是一种更好的抗惊厥药。积极的 在五名患者之一中，已经观察到对氮岛的反应 快速但不是超级自行车障碍，这在一个on- 离合（B-A-B）设计。 三名超毛线快速循环的患者 （超级骑自行车）显示对双重响应 尼莫地平的盲目给药。 部分响应者被确认 在B-A-B设计中，通过 添加卡马西平。 由于卡马西平最近是 描述的是抑制通过NMDA受体中的钙涌入 小脑颗粒细胞，这些数据增加了药物的可能性 对钙通道的不同影响可能有用 患者。 一名经常出现较短抑郁症的患者反应 在安慰剂上复发到尼莫地平的盲人机构 替换，并以恢复活性药物的重新辩护（B-A-B- 一个）;当维拉帕米（Verapamil） 取代氮岛。 这些数据表明进一步的实用性 探索敏捷性情感中敏迪平的临床特征 疾病和钙代谢改变的潜力 疾病。