β-Adrenergic receptor and platelet inhibitory activities of a new series of trimetoquinol and related benzazepine analogs

Gamal Shams, Karl J. Romstedt, Laura A. Lust, Michael T. Clark, Duane Miller, Dennis R. Feller

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A series of dimethoxy and methylenedioxy analogs of trimetoquinol (TMQ) and structurally related 7-membered ring benzazepines (BA) were evaluated for their pharmacological effects in β-adrenergic (atria, trachea) and thromboxane A2/prostaglandin H2 receptor systems (aorta, platelets). Results show that both the 6,7-dihydroxy (catechol) moiety of trimetoquinol and an intact tetrahydroisoquinoline nucleus are essential for maintaining potent β-stimulating and antithromboxane A2 activities. By contrast, ring enlargement, as in the BA analogs, or masking of the catechol with dimethoxy or methylenedioxy functional groups enhanced the potency of inhibitors on thromboxane A2-independent activation of human platelets induced by bacterial phospholipase C (PLC). The selective blockade of this pathway by these compounds suggests that they may represent a new and novel class of antiplatelet drugs.

Original languageEnglish (US)
Pages (from-to)323-330
Number of pages8
JournalGeneral Pharmacology
Volume28
Issue number2
DOIs
StatePublished - Feb 1 1997

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Tretoquinol
Benzazepines
Adrenergic Receptors
Blood Platelets
Prostaglandin H2 Receptors Thromboxane A2
Tetrahydroisoquinolines
Thromboxane A2
Platelet Aggregation Inhibitors
Platelet Activation
Type C Phospholipases
Trachea
varespladib methyl
Adrenergic Agents
Aorta
Pharmacology
catechol

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

β-Adrenergic receptor and platelet inhibitory activities of a new series of trimetoquinol and related benzazepine analogs. / Shams, Gamal; Romstedt, Karl J.; Lust, Laura A.; Clark, Michael T.; Miller, Duane; Feller, Dennis R.

In: General Pharmacology, Vol. 28, No. 2, 01.02.1997, p. 323-330.

Research output: Contribution to journalArticle

Shams, Gamal ; Romstedt, Karl J. ; Lust, Laura A. ; Clark, Michael T. ; Miller, Duane ; Feller, Dennis R. / β-Adrenergic receptor and platelet inhibitory activities of a new series of trimetoquinol and related benzazepine analogs. In: General Pharmacology. 1997 ; Vol. 28, No. 2. pp. 323-330.
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