Use of [3H]trimetoquinol as a radioligand in human platelets: interaction with putative endoperoxide/thromboxane A2 receptor sites.

  title={Use of [3H]trimetoquinol as a radioligand in human platelets: interaction with putative endoperoxide/thromboxane A2 receptor sites.},
  author={Chang Ho Ahn and Lane J. Wallace and D. D. Miller and Dennis R. Feller},
  journal={Thrombosis research},
  volume={50 3},
We have recently shown that trimetoquinol [1-(3,4,5-trimethoxybenzyl)-6,7-dihydroxy-1,2,3,4- tetrahydroisoquinoline; TMQ] is a potent and stereoselective [R(+)-isomer greater than S(-)-isomer] antagonist of aggregation induced by thromboxane A2 and stable epoxymethano PGH2 analogues (U46619; U44069) in human platelets. The present study was undertaken to characterize the pharmacological specificity of binding sites for racemic- [3H]TMQ in washed human platelets. Specific binding of [3H]TMQ… 
Pharmacologic antagonism of thromboxane A2 receptors by trimetoquinol analogs in vitro and in vivo.
In vivo antithrombotic potencies of these compounds were consistent with the in vitro potencies as TXA2 receptor antagonists in platelet systems and protected animals against death.
Halogen-substituted trimetoquinol analogs as thromboxane A2 receptor antagonists in platelets and aorta.
It is demonstrated that the primary mechanism of antiplatelet action of TMQ analogs is related to a blockade of TXA2 receptor sites, and ring-halogenated TMq analogs distinguish betweenTXA2-mediated functional responses in vascular smooth muscle and platelets.
Synthesis and in vitro platelet aggregation and TP receptor binding studies on bicyclic 5,8-ethanooctahydroisoquinolines and 5,8-ethanotetrahydroisoquinolines.
Eighteen novel bicyclic 1-substituted benzyl octahydro- and tetrahydroisoquinolines were synthesized and evaluated for human thromboxane A(2)/prostaglandin H(2) (TP) receptor affinity and antagonism
Prostanoid receptor antagonists: development strategies and therapeutic applications
This review is intended to provide overviews of each antagonist class (including prostamide antagonists), covering major development strategies and current and potential clinical usage.
International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress
The DP2 receptor, also termed CRTH2, has little structural resemblance to DP1 and other receptors described in the original prostanoid receptor classification and is anticipated to lead to novel therapeutic entities.


Stereo-dependent inhibition of human platelet function by the optical isomers of trimetoquinol.
These data, together with the ability of the TMQ stereoisomers to selectively inhibit TxA 2 -induced aggregation, suggest that TMQ is an inhibitor of endoperoxide or TXA 2 action, e.g. a thromboxane A 2 receptor antagonist.
Specific binding of the thromboxane A2 antagonist 13-azaprostanoic acid to human platelet membranes.
Findings indicate that trans 13-APA binds to a specific site on the platelet membrane which presumably represents the thromboxane A2/prostaglandin H2 receptor.
Characterization of U46619 binding in unactivated, intact human platelets and determination of binding site affinities of four TXA2/PGH2 receptor antagonists (13-APA, BM 13.177, ONO 3708 and SQ 29,548).
Findings are consistent with the notion that these compounds all act as competitive antagonists at the level of the platelet TXA2/PGH2 receptor.
Identification of a putative thromboxane A2/prostaglandin H2 receptor in human platelet membranes.
The binding of the competitive thromboxane A2/prostaglandin H2 (TXA2/PGH2) antagonist and [125I]PTA-OH to membranes prepared from human platelets was characterized, consistent with the notion that this binding site may represent the platelet TXA-OH receptor.
Effect of trimetoquinol analogs for antagonism of endoperoxide/thromboxane A2-mediated responses in human platelets and rat aorta.
It is concluded that selectivity for these two pharmacological properties of TMQ can be achieved by appropriate stereochemical modification of the tetrahydroisoquinoline nucleus.
A novel approach for the study of thromboxane A2 and prostaglandin H2 receptors using an 125I-labeled ligand.
Observations show that the omega side chain of eicosanoid analogs can be substituted with a phenolic group, iodinated, and retain biological activity and may be utilized to study thromboxane A2 or prostaglandin H2 receptors.
Ligand binding to thromboxane receptors on human platelets: correlation with biological activity
1 The preparation of enantiomerically pure [3H]‐15 (S) 9, 11‐epoxymethano PGH2 (a thromboxane A2‐like agonist) has enabled the binding of ligands to the thromboxane receptor of the human platelet to
Synthesis and platelet antiaggregatory activity of trimetoquinol analogs as endoperoxide/thromboxane A2 antagonists.
Results suggest that the putative sites of interaction for the trimethoxy ring system of TMQ in platelet systems will tolerate large, lipid soluble groups but will not tolerate large changes in the electronic characteristics of the ring system.
Antagonism of prostaglandin-mediated responses in platelets and vascular smooth muscle by 13-azaprostanoic acid analogs. Evidence for selective blockade of thromboxane A2 responses.
Results show that expansion of the five- Membered ring of APA to the six-membered ring analogs (HAPA) led to a retention of potent inhibitory activity against U46619 in human platelets and rat vascular smooth muscle, and these azaprostanoic acid analogs act as selective endoperoxide (U46619)/thromboxane A2 antagonists in these two tissues.
Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides.
An unstable [t1/2 at 37 degrees = 32 +/- 2 (SD) sec] intermediate, thromboxane A2, was detected in the conversion of prostaglandin G2 into