Kramer M S, Cutler N R, Ballenger J C, Patterson W M, Mendels J, Chenault A, Shrivastava R, Matzura-Wolfe D, Lines C, Reines S
Merck Research Laboratories, West Point, PA 19486, USA.
Biol Psychiatry. 1995 Apr 1;37(7):462-6. doi: 10.1016/0006-3223(94)00190-E.
The functional role of cholecystokinin in the central nervous system is unknown. The tetra peptide CCK-4 was previously observed to induce panic attacks in a majority of normal volunteers and patients with panic disorder. Furthermore, it had been demonstrated that pretreatment with 10-50 mg of L-365,260, a selective CCKB antagonist, blocked CCK-4 induced panic in patients with panic disorder. Therefore, the present multicenter, placebo-controlled, double-blind trial was designed to investigate the efficacy of L-365,260, a CCKB antagonist, in patients with panic disorder with or without agoraphobia. Following a 1-week, single-blind placebo period, 88 patients were randomized to double-blind treatment in which they received either L-365,260, 30 mg qid, or placebo for 6 weeks. At the dose tested, there were no clinically significant differences between L-365,260 and placebo in global improvement ratings, Hamilton anxiety rating scale scores, panic attack frequency, panic attack intensity, or disability measures. The possible reasons for lack of effect with L-365,260 are discussed.
胆囊收缩素在中枢神经系统中的功能作用尚不清楚。先前观察到四肽CCK - 4能在大多数正常志愿者和惊恐障碍患者中诱发惊恐发作。此外,已经证明,用10 - 50毫克的L - 365,260(一种选择性CCKB拮抗剂)进行预处理,可以阻断CCK - 4在惊恐障碍患者中诱发的惊恐发作。因此,本项多中心、安慰剂对照、双盲试验旨在研究CCKB拮抗剂L - 365,260对伴有或不伴有广场恐怖症的惊恐障碍患者的疗效。在为期1周的单盲安慰剂期后,88名患者被随机分配到双盲治疗组,他们接受L - 365,260(30毫克,每日四次)或安慰剂治疗6周。在所测试的剂量下,L - 365,260和安慰剂在总体改善评分、汉密尔顿焦虑评定量表得分、惊恐发作频率、惊恐发作强度或功能障碍测量方面没有临床显著差异。文中讨论了L - 365,260无效的可能原因。