Orsetti M
Institute of Pharmacology and Pharmacognosy, Pharmacy School, University of Turin, Torino, Italy.
Agents Actions. 1988 Dec;25(3-4):291-5. doi: 10.1007/BF01965034.
The possibility that the aromatic component in the classical H2-antagonists might not be essential for histamine H2-receptor blockade has been investigated. In the ranitidine series the removal of the furan ring is accompanied by a drastic decrease in H2-blocking activity, but not by its disappearance (compound HB5:KB on guinea pig isolated atria 31.6 microM) whereas in the lamtidine analogues the substitution of the phenyl moiety with the more reduced pi-bonded CH3-C = N-area generates a compound whose activity is comparable to that of cimetidine (KB on atria 1.12 microM; ID50 in the lumen-perfused stomach of the anaesthetized rat 3.61 mumol/kg i.v.). The results also indicate that the diaminofurazan group confers high affinity at the histamine H2-receptor. It is concluded that the aromatic portion of H2-antagonists related to ranitidine and lamtidine is not a minimal requisite for activity when an appropriate polar group is used as an "urea equivalent" moiety.
经典H2拮抗剂中的芳香成分对于组胺H2受体阻断作用可能并非必不可少，这一可能性已得到研究。在雷尼替丁系列中，呋喃环的去除伴随着H2阻断活性的急剧下降，但并非完全消失（化合物HB5：豚鼠离体心房的KB为31.6微摩尔），而在兰替丁类似物中，用还原程度更高的π键合CH3-C=N区域取代苯基部分，生成了一种活性与西咪替丁相当的化合物（心房的KB为1.12微摩尔；麻醉大鼠经肠腔灌注胃的ID50为静脉注射3.61微摩尔/千克）。结果还表明，二氨基呋咱基团赋予了对组胺H2受体的高亲和力。得出的结论是，当使用合适的极性基团作为“脲等效物”部分时，与雷尼替丁和兰替丁相关的H2拮抗剂的芳香部分并非活性的最低必要条件。
