Structure-activity relationships of 4'-O-substituted 1-benzylisoquinolines with respect to their actions on the cell membrane of blood platelets and erythrocytes.
4'-O-Substituted 1-benzyl-2-methyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines inhibited the collagen-induced activation (aggregation and ATP secretion) of rabbit platelets and transformed the shape of human erythrocytes in a dose-dependent manner. Both effects increased with increasing number of carbon atoms of the 4'-substituted hydrocarbon moiety. The incorporation of these compounds into the erythrocyte membrane was also dependent on the number of carbon atoms of the 4'-substituted radical. The most potent phenoxy derivative suppressed arachidonic acid release from membrane phospholipids but had no effect on arachidonic acid metabolism in platelets. This indicated that the effects are comparable to those of a natural bisbenzylisoquinoline, cepharanthine. These effects appear to be due to a perturbing action on the membrane lipid bilayer.
D000255:Adenosine Triphosphate / Q000097:blood; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D044182:Benzylisoquinolines; D001792:Blood Platelets / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010743:Phospholipids / Q000097:blood; D011804:Quinolines / Q000494:pharmacology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D052117:Benzodioxoles
D000255:Adenosine Triphosphate; D000470:Alkaloids; D016718:Arachidonic Acid; D001095:Arachidonic Acids; D044182:Benzylisoquinolines; D003094:Collagen; D010743:Phospholipids; D011804:Quinolines; C006947:cepharanthine; D052117:Benzodioxoles