Action of ebrotidine, ranitidine and cimetidine on the specific binding to histamine H1- and H2-receptors.
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.
Agut
J
J
Centro de Investigación Farmacéutica Grupo Ferrer, Barcelona, Spain.
Sánchez
J C
JC
Sacristán
A
A
Ortiz
J A
JA
D000818:Animals; D001557:Benzenesulfonates / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D002927:Cimetidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D003864:Depression, Chemical; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008297:Male; D011485:Protein Binding / Q000187:drug effects; D011738:Pyrilamine / Q000378:metabolism; D011899:Ranitidine / Q000494:pharmacology*; D011969:Receptors, Histamine H1 / Q000187:drug effects / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D014316:Tritium
D001557:Benzenesulfonates; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D013844:Thiazoles; D014316:Tritium; D002927:Cimetidine; D011899:Ranitidine; C023990:tiotidine; D011738:Pyrilamine; C075156:ebrotidine