Department of Clinical Pharmacy Practice and Health Care Management, Meijo University, Nagoya, Japan.
Arch Dermatol Res. 2012 May;304(4):263-72. doi: 10.1007/s00403-011-1192-2. Epub 2011 Dec 1.
Since most first-generation antihistamines have undesirable sedative effects on the central nervous systems (CNS), newer (second-generation) antihistamines have been developed to improve patients' quality of life. However, there are few reports that directly compare the antihistaminic efficacy and impairment of psychomotor functions. We designed a double-blind, placebo controlled, crossover study to concurrently compare the clinical effectiveness of promethazine, a first-generation antihistamine, and fexofenadine and olopatadine, second-generation antihistamines, by measuring their potency as peripheral inhibitors of histamine-induced wheal and flare. Further, we investigated their sedative effects on the CNS using a battery of psychomotor tests. When single therapeutic doses of fexofenadine (60 mg), olopatadine (5 mg) and promethazine (25 mg) were given in a double-blind manner to 24 healthy volunteers, all antihistamines produced a significant reduction in the wheal and flare responses induced by histamine. In the comparison among antihistamines, olopatadine showed a rapid inhibitory effect compared with fexofenadine and promethazine, and had a potent effect compared with promethazine. In a battery of psychomotor assessments using critical flicker fusion, choice reaction time, compensatory tracking, rapid visual information processing and a line analogue rating scale as a subjective assessment of sedation, promethazine significantly impaired psychomotor function. Fexofenadine and olopatadine had no significant effect in any of the psychomotor tests. Promethazine, fexofenadine and olopatadine did not affect behavioral activity, as measured by wrist actigraphy. These results suggest that olopatadine at a therapeutic dose has greater antihistaminergic activity than promethazine, and olopatadine and fexofenadine did not cause cognitive or psychomotor impairment.
由于第一代抗组胺药对中枢神经系统（CNS）具有不理想的镇静作用，因此开发了新型（第二代）抗组胺药以提高患者的生活质量。但是，很少有报道直接比较抗组胺作用和精神运动功能障碍。我们设计了一项双盲，安慰剂对照，交叉研究，通过测量其作为组胺诱导的风团和红斑的外周抑制剂的效力，同时比较第一代抗组胺药苯海拉明和第二代抗组胺药非索非那定和奥洛他定的临床疗效。此外，我们使用一系列精神运动测试研究了它们对中枢神经系统的镇静作用。当以双盲方式给 24 名健康志愿者单次治疗剂量的非索非那定（60mg），奥洛他定（5mg）和苯海拉明（25mg）时，所有抗组胺药均可显着减少组胺诱导的风团和红斑反应。在抗组胺药的比较中，奥洛他定与非索非那定和苯海拉明相比具有更快的抑制作用，并且与苯海拉明相比具有更强的作用。在使用临界闪烁融合，选择反应时间，代偿性跟踪，快速视觉信息处理和线性模拟评分量表作为镇静的主观评估的一系列精神运动评估中，苯海拉明显着损害了精神运动功能。非索非那定和奥洛他定在任何精神运动测试中均无明显作用。苯海拉明，非索非那定和奥洛他定均未对手腕活动记录仪测量的行为活动产生影响。这些结果表明，奥洛他定在治疗剂量下具有比苯海拉明更强的抗组胺作用，并且奥洛他定和非索非那定不会引起认知或精神运动损害。
