Efficacy and tolerability of a selective α2C-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients -: A single-center, double-blind, placebo-controlled, randomized crossover study
Efficacy and tolerability of a selective α2C-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients -: A single-center, double-blind, placebo-controlled, randomized crossover study
复制标题
DOI：
10.1002/art.20665
复制
发表时间：
2004-12-01
影响因子：
--
通讯作者：
Czerwiec, FS
中科院分区：
文献类型：
--
作者：
Wise, RA;Wigley, FA;Czerwiec, FS
目标。OPC-28326是一种选择性a-肾上腺素能拮抗剂，优先结合α (2C)-肾上腺素能受体（α (2C)- ar）亚型。本研究观察了OPC-28326对硬皮病继发雷诺现象患者急性冷激后皮肤温度和数字血流量的影响。该研究设计为单中心、双盲、安慰剂对照、随机、3期交叉研究，OPC-28326（口服剂量为10mg或40mg）或安慰剂。主要结果测量是在基线数字皮肤温度下恢复50%和70%的跌倒（由冷挑战引起）所需的时间。13名入组患者中有12名完成了研究。OPC-28326 40-mg剂量组达到攻击前数字皮肤温度变化50%和70%恢复的平均时间比安慰剂组短（50%恢复在5.8分钟vs 10.0分钟[P = 0.02]； 70%恢复在13.8分钟vs 19.5分钟[P = 0.01]）。10 mg OPC-28326组的恢复时间也更短，但与安慰剂组的差异不显著（9.0分钟恢复50%，10.0分钟恢复50% [P = 0.651； 15.3分钟恢复70%，19.5分钟恢复70% [P = 0.07]）。总数字血流量在冷刺激前和服用40mg OPC-28326后，与安慰剂后相比有降低的趋势，但差异不显著。40灵OPC-28326组比10灵OPC-28326组或安慰剂组更频繁地报告可能与药物相关的症状，但没有严重或持续的症状。在本研究中，OPC-28326剂量为10 ling和40 ling时耐受性良好。40 mg OPC-28326后皮肤温度恢复时间较短，表明选择性α (2C)-AR阻断可改善继发硬皮病雷诺现象患者在降温恢复过程中的数字皮肤灌注。
Objective. OPC-28326 is a selective a-adrenergic antagonist with preferential binding to the alpha(2C)- adrenergic receptor (alpha(2C)-AR) subtype. This study observed the effect of OPC-28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma.Methods. The study was designed as a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of OPC-28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature.Results. Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC-28326 40-mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC-28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.651; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC-28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug-related were reported more frequently with 40 ling OPC-28326 than with 10 ling OPC-28326 or with placebo, but none were serious or sustained.Conclusion. OPC-28326 at doses of 10 ling and 40 ling was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC-28326 suggests that selective alpha(2C)-AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.