Misawa M, Kanai Y
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Arzneimittelforschung. 1991 Nov;41(11):1145-9.
Recently, mast cell stabilizers, so called antiallergic drugs, that also have blocking effects on receptors for chemical mediators (CM) have been developed. The present study investigated the effects of a new antiallergic drug, epinastine (3-amino-9,13b-dihydro-1H-dibenz[c,f]imidazol [1,5-a]azepine hydrochloride, WAL 810 CL; CAS 80012-43-7) on the in vivo bronchoconstriction (BC) induced by several CM as compared with those of other antiallergic drugs such as ketotifen, azelastine and oxatomide. Male Hartley guinea pigs were used. The BC was measured with a modified Konzett-Rössler method and expressed as a change in ventilation overflow (VO) under anesthesia. Antiallergic drugs were given orally 1 h before i.v. administration of CM. I.v. administrations of histamine (His), U-46619 (thromboxane A2 mimetic), leukotriene D4 (LTD4), prostaglandin D2 (PGD2), substance P (SP), neurokinin A (NKA), bradykinin (BK) and endothelin-1 (ET-1) increased VO in a dose dependent manner. The potency was as follows; ET-1 greater than LTD4 greater than NKA much greater than U-46619 greater than SP greater than His greater than BK much greater than PGD2. All the antiallergic drugs used markedly inhibited the His-induced BC. Epinastine, ketotifen and azelastine also significantly inhibited the BK-induced BC; epinastine had the strongest anti-BK effect among them. On the other hand, the four antiallergic drugs did not inhibit the BC induced by the other CM except for His and BK. Based on the above results, it is suggested that epinastine possesses anti-His and BK effects, and therefore could be promising as a new antiallergic drug without sedative effect.
最近，已开发出肥大细胞稳定剂，即所谓的抗过敏药物，其对化学介质（CM）受体也具有阻断作用。本研究调查了一种新型抗过敏药物依巴斯汀（3-氨基-9,13b-二氢-1H-二苯并[c,f]咪唑[1,5-a]氮杂卓盐酸盐，WAL 810 CL；CAS 80012-43-7）与其他抗过敏药物如酮替芬、氮卓斯汀和奥沙米特相比，对几种CM诱导的体内支气管收缩（BC）的影响。使用雄性Hartley豚鼠。采用改良的Konzett-Rössler方法测量BC，并表示为麻醉下通气溢出（VO）的变化。在静脉注射CM前1小时口服给予抗过敏药物。静脉注射组胺（His）、U-46619（血栓素A2类似物）、白三烯D4（LTD4）、前列腺素D2（PGD2）、P物质（SP）、神经激肽A（NKA）、缓激肽（BK）和内皮素-1（ET-1）以剂量依赖性方式增加VO。效力如下：ET-1大于LTD4大于NKA远大于U-46619大于SP大于His大于BK远大于PGD2。所有使用的抗过敏药物均显著抑制His诱导的BC。依巴斯汀、酮替芬和氮卓斯汀也显著抑制BK诱导的BC；依巴斯汀在其中具有最强的抗BK作用。另一方面，除His和BK外，这四种抗过敏药物不抑制其他CM诱导的BC。基于上述结果，提示依巴斯汀具有抗His和BK作用，因此有望成为一种无镇静作用的新型抗过敏药物。
