Verdier F, Chazal I, Descotes J
Pharmakon Europe, L'Arbresle, France.
Toxicology. 1994 Sep 22;93(1):55-61. doi: 10.1016/0300-483x(94)90196-1.
Immediate hypersensitivity (or anaphylactic) reactions can be caused by large molecules which are directly immunogenic or by smaller molecules which bind to macromolecular carriers and act as haptens. To reproduce these reactions in animals, either systemic or local models are used in actively or passively sensitized animals, respectively. Several attempts have been made to detect the potential of new drugs and chemicals to induce anaphylactic reactions. Protocols using the inhalation of reactive low-molecular-weight compounds produced clinical symptoms in the guinea-pig. An intralaboratory validation study was initiated using a panel of six positive and one negative model compounds in a guinea-pig model combining systemic and local anaphylaxis. Anaphylactic reactions to positive model compounds were obtained only when the molecular weight was approximately 3000 or more. Overall, published results indicate that the potential to induce immediate hypersensitivity reactions can be detected as far as large-molecular-weight molecules are concerned--in contrast to the majority of low-molecular-weight drugs and chemicals.
速发型超敏反应（或过敏反应）可由具有直接免疫原性的大分子引起，也可由与大分子载体结合并作为半抗原起作用的小分子引起。为在动物中重现这些反应，分别在主动或被动致敏的动物中使用全身或局部模型。人们已多次尝试检测新药和化学物质诱导过敏反应的可能性。使用吸入反应性低分子量化合物的方案在豚鼠中产生了临床症状。在豚鼠模型中结合全身和局部过敏反应，使用一组六种阳性和一种阴性模型化合物启动了一项实验室内部验证研究。仅当分子量约为3000或更大时，才获得对阳性模型化合物的过敏反应。总体而言，已发表的结果表明，就大分子重量分子而言，可以检测到诱导速发型超敏反应的可能性——这与大多数低分子量药物和化学物质形成对比。
