Stereo-dependent inhibition of human platelet function by the optical isomers of trimetoquinol

Joseph R. Mayo, Stephen S. Navran, Huzoor-Akbar, Duane Miller, Dennis R. Feller

Research output: Contribution to journalArticle

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Abstract

The stereoisomers of trimetoquinol [1-(3',4',5'-trimethoxybenzyl)-6-7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; TMQ] were shown to have potent and selective inhibitory effects on human platelet function in vitro. the R(+)-isomer was 12.1-, 12.3-, 39.2-, 82.9- and 36.0-fold more effective than the S(-)-isomer as an inhibitor of aggregation induced by arachidonic acid (AA), collagen, the epoxymethano-PGH2 analogs U44069 and U46619, and thromboxane A; (TxA2) respectively. the concentrations of the R(+)-isomer that produced 50 percent inhibition (IC50) of platelet aggregation were 4.2, 4.3, 1.4, 0.14 and 0.64 μM using AA, collagen, U44069, U46619, and TxA20 as respective inducers. the graphical approximation of an inhibitory Constant (Ki = 0.13 μM) for the effect of TMQ on U46619-induced aggregation suggested that a competitive-like inhibition was operative. In other experiments, platelet aggregation and serotonin release induced by U46619 were inhibited differentially by the TMQ stereoisomers with nearly identical concentration-response curves. In addition, racemicTMQ blocked the secondary phase of platelet aggregation and serotonin release induced by ADP. These data, together with the ability of the TMQ stereoisomers to selectively inhibit TxA2-induced aggregation, suggest that TMQ is an inhibitor of endoperoxide or TxA2 action, e.g. a thromboxane A2 receptor antagonist.

Original languageEnglish (US)
Pages (from-to)2237-2241
Number of pages5
JournalBiochemical Pharmacology
Volume30
Issue number16
DOIs
StatePublished - Aug 15 1981
Externally publishedYes

Fingerprint

Tretoquinol
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Platelets
Isomers
Stereoisomerism
Blood Platelets
Agglomeration
Platelet Aggregation
Arachidonic Acid
Serotonin
Collagen
Prostaglandin H2 Receptors Thromboxane A2
Prostaglandin H2
Thromboxanes
Adenosine Diphosphate
Inhibitory Concentration 50

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

Cite this

Stereo-dependent inhibition of human platelet function by the optical isomers of trimetoquinol. / Mayo, Joseph R.; Navran, Stephen S.; Huzoor-Akbar, ; Miller, Duane; Feller, Dennis R.

In: Biochemical Pharmacology, Vol. 30, No. 16, 15.08.1981, p. 2237-2241.

Research output: Contribution to journalArticle

Mayo, Joseph R. ; Navran, Stephen S. ; Huzoor-Akbar, ; Miller, Duane ; Feller, Dennis R. / Stereo-dependent inhibition of human platelet function by the optical isomers of trimetoquinol. In: Biochemical Pharmacology. 1981 ; Vol. 30, No. 16. pp. 2237-2241.
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