BETA-ADRENERGIC-RECEPTOR AND PLATELET INHIBITORY ACTIVITIES OF A NEW SERIES OF TRIMETOQUINOL AND RELATED BENZAZEPINE ANALOGS

1. A series of dimethoxy and methylenedioxy analogs of trimetoquinol ( TMR) and structurally related 7-membered ring benzazepines (BA) were e valuated for their pharmacological effects in beta-adrenergic (atria, trachea) and thromboxane A(2)/prostaglandin H-2 receptor systems (aort a, platelets). 2. Results show that both the 6,7-dihydroxy (catechol) moiety of trimetoquinol and an intact tetra hydroisoquinoline nucleus are essential for maintaining potent beta-stimulating and antithrombox ane A(2) activities. 3. By contrast, ring enlargement, as in the BA an alogs, or masking of the catechol with dimethoxy or methylenedioxy fun ctional groups enhanced the potency of inhibitors on thromboxane A(2)- independent activation of human platelets induced by bacterial phospho lipase C (PLC). 4. The selective blockade of this pathway by these com pounds suggests that they may represent a new and novel class of antip latelet drugs. Copyright (C) 1997 Elsevier Science Inc.