Onnen I, Olive G
Eur J Pharmacol. 1983 Jun 3;90(2-3):185-91. doi: 10.1016/0014-2999(83)90236-4.
Guinea pig ileum developed in vitro a progressive desensitization to the antihistaminic agents mepyramine and benadryl. This desensitization had uncommon characteristics: (1) at the 6.5-9 h period of the experiments, it consisted only of a decreased rate of action of the drugs (1.66 fold and 2 fold increases in the 2 min Kb value of mepyramine and benadryl respectively), without variation in the equilibrium Kb values; (2) it was not a drug effect since control strips (strips exposed to the first dose of antihistaminic agent after 5.5 h in vitro) also showed a decreased rate of action of the drugs (1.58 fold and 1.6 fold increases in the 2 min Kb value of mepyramine and benadryl respectively), without variation in the Kbe values. The desensitization also did not depend on the bathing medium or on the amount of available histamine receptors. The only explanation of the desensitization is a slowing in the antihistaminic agent-receptor reaction either in its access stage or less probably in its interaction stage.
豚鼠回肠在体外对组胺拮抗剂美吡拉敏和苯海拉明产生了渐进性脱敏。这种脱敏具有不同寻常的特点：（1）在实验的6.5 - 9小时期间，它仅表现为药物作用速率降低（美吡拉敏和苯海拉明的2分钟Kb值分别增加1.66倍和2倍），而平衡Kb值没有变化；（2）这不是药物效应，因为对照条带（在体外5.5小时后暴露于第一剂组胺拮抗剂的条带）也显示出药物作用速率降低（美吡拉敏和苯海拉明的2分钟Kb值分别增加1.58倍和1.6倍），而Kbe值没有变化。脱敏也不依赖于浴液介质或可用组胺受体的数量。对脱敏的唯一解释是组胺拮抗剂 - 受体反应在其接触阶段减慢，或者在其相互作用阶段减慢的可能性较小。
