Yanai Kazuhiko, Yoshikawa Takeo, Church Martin K
Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
Cyclotron and Radioisotope Center (CYRIC), Tohoku University, Sendai, Japan.
Curr Top Behav Neurosci. 2022;59:193-214. doi: 10.1007/7854_2021_265.
H receptor antagonists, known as H-antihistamines (AHs), inactivate the histamine H-receptor thereby preventing histamine causing the primary symptoms of allergic diseases, such as atopic dermatitis, pollinosis, food allergies, and urticaria. AHs, which are classified into first-generation (fgAHs) and second-generation (sgAHs) antihistamines, are the first line of treatment for allergic diseases. Although fgAHs are effective, they cause adverse reactions such as potent sedating effects, including drowsiness, lassitude, and cognitive impairment; anticholinergic effects, including thirst and tachycardia. Consequently, the use of fgAHs is not recommended for allergic diseases. Today, sgAHs, which are minimally sedating and, therefore, may be used at more effective doses, are the first-line treatment for alleviating the symptoms of allergic diseases. Pharmacologically, the use of sedating fgAHs is limited to antiemetics, anti-motion sickness drugs, and antivertigo drugs. The use of histamine H-receptor occupancy (HRO) based on positron emission tomography (PET) has been developed for the evaluation of brain penetrability. Based on the results of the HRO-PET studies, non-brain-penetrating AHs (nbpAHs) have recently been reclassified among sgAHs. The nbpAHs are rapidly acting and exhibit minimal adverse reactions and, thus, are considered first-line drugs for allergic diseases. In this review, we will introduce recent topics on the pharmacodynamics and pharmacokinetics of AHs and make recommendations for the use of nbpAHs as first-line treatment options for allergic diseases.
H受体拮抗剂，即H抗组胺药（AHs），可使组胺H受体失活，从而防止组胺引发过敏性疾病的主要症状，如特应性皮炎、花粉症、食物过敏和荨麻疹。AHs分为第一代（fgAHs）和第二代（sgAHs）抗组胺药，是过敏性疾病的一线治疗药物。尽管fgAHs有效，但它们会引起不良反应，如强效镇静作用，包括嗜睡、倦怠和认知障碍；抗胆碱能作用，包括口渴和心动过速。因此，不建议将fgAHs用于治疗过敏性疾病。如今，sgAHs的镇静作用极小，因此可以使用更有效的剂量，是缓解过敏性疾病症状的一线治疗药物。从药理学角度来看，具有镇静作用的fgAHs仅限于用作止吐药、抗晕动病药物和抗眩晕药物。基于正电子发射断层扫描（PET）的组胺H受体占有率（HRO）评估方法已被开发用于评估药物的脑渗透性。根据HRO-PET研究结果，非脑渗透性AHs（nbpAHs）最近在sgAHs中被重新分类。nbpAHs起效迅速，不良反应极小，因此被视为过敏性疾病的一线药物。在本综述中，我们将介绍AHs的药效学和药代动力学的最新研究进展，并就将nbpAHs用作过敏性疾病的一线治疗方案提出建议。
