White J M
Life Sci. 1985 Sep 23;37(12):1145-53. doi: 10.1016/0024-3205(85)90358-3.
Rats were trained to discriminate i.p. injections of mepyramine (10.0 mg/kg) from saline. Correct responses on one of the two levers were reinforced with access to a solution of sweetened condensed milk. A level of at least 27 correct responses in the first 30 (90%) was required in consecutive saline and mepyramine training sessions before a test session was conducted. Amongst the antihistamines, mepyramine, tripelennamine and chlorpheniramine all produced dose-related responding on the mepyramine lever, reaching a maximum of over 90% mepyramine-appropriate responses. Both tripelennamine and chlorpheniramine were more potent than the training drug. Diphenhydramine and promethazine produced high levels of mepyramine-appropriate responses, but the 90% level was not reached with any dose tested. The dextrorotatory isomer of chlorpheniramine, which binds with high affinity to H1-receptors, was approximately twice as potent as the racemic mixture. The anticholinergic, scopolamine, and the local anaesthetic, procaine, produced only low levels of mepyramine-appropriate responses. However, 10.0 mg/kg of the anti-depressant imipramine produced over 90% mepyramine-appropriate responses. These results suggest that a discrimination can be formed on the basis of the specific H1-receptor antagonist activity of mepyramine.
训练大鼠区分腹腔注射的美吡拉敏（10.0毫克/千克）和生理盐水。在两个杠杆之一上的正确反应通过给予甜炼乳溶液来强化。在进行测试之前，连续的生理盐水和美吡拉敏训练 sessions 中，前30次（90%）中至少要有27次正确反应。在抗组胺药中，美吡拉敏、曲普利啶和氯苯那敏在美吡拉敏杠杆上均产生剂量相关反应，美吡拉敏适宜反应的最大值超过90%。曲普利啶和氯苯那敏均比训练药物更有效。苯海拉明和异丙嗪产生了高水平的美吡拉敏适宜反应，但在所测试的任何剂量下均未达到90%的水平。与H1受体具有高亲和力的氯苯那敏右旋异构体的效力约为消旋混合物的两倍。抗胆碱能药物东莨菪碱和局部麻醉药普鲁卡因仅产生低水平的美吡拉敏适宜反应。然而，10.0毫克/千克的抗抑郁药丙咪嗪产生了超过90%的美吡拉敏适宜反应。这些结果表明，可以基于美吡拉敏的特异性H1受体拮抗剂活性形成一种辨别。
