Agut J, Sánchez J C, Sacristán A, Ortiz J A
Centro de Investigación Farmacéutica Grupo Ferrer, Barcelona, Spain.
Arzneimittelforschung. 1997 Apr;47(4A):447-9.
Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)-4-thiazolyl]methyl]thio] ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542), a selective H2-receptor antagonist, has proved to competitively inhibit the positive chronotropism induced by histamine in isolated guinea pig atrium. The affinity of ebrotidine to histamine H1- and H2-receptors through the displacement of 3H-pyrilamine and 3H-thiotidine binding to guinea pig cerebellum and brain cortex membranes was investigated. Ebrotidine displaced 3H-thiotidine specific binding to histamine H2-receptors (Ki: 127.5 nmol/l), showing a higher affinity (p < 0.05) than ranitidine (Ki: 190.0 nmol/l) and cimetidine (Ki: 246.1 nmol/l). None of the three substances displaced 3H-pyrilamine binding to H1-receptors (Ki: > 5000 nmol/l). The results showed that ebrotidine is a drug with a high affinity for H2 receptors, higher than cimetidine and ranitidine.
依布替丁（N-[(E)-[[2-[[[2-[(二氨基亚甲基)-4-噻唑基]甲基]硫代]乙基]氨基]亚甲基]-4-溴苯磺酰胺，CAS 100981-43-9，FI-3542），一种选择性H2受体拮抗剂，已被证明能在离体豚鼠心房中竞争性抑制组胺诱导的正性变时作用。通过3H-吡拉明和3H-硫替丁与豚鼠小脑和大脑皮质膜结合的置换，研究了依布替丁对组胺H1和H2受体的亲和力。依布替丁置换了3H-硫替丁与组胺H2受体的特异性结合（Ki：127.5 nmol/L），显示出比雷尼替丁（Ki：190.0 nmol/L）和西咪替丁（Ki：246.1 nmol/L）更高的亲和力（p < 0.05）。这三种物质均未置换3H-吡拉明与H1受体的结合（Ki：> 5000 nmol/L）。结果表明，依布替丁是一种对H2受体具有高亲和力的药物，高于西咪替丁和雷尼替丁。
