Pharmacological evaluation of the β-adrenoceptor agonist and thromboxane receptor blocking properties of 1-benzyl substituted trimetoquinol analogues

Gamal Shams, Karl J. Romstedt, Mark A. Gerhardt, Marc W. Harrold, Duane Miller, Dennis R. Feller

Research output: Contribution to journalArticle

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Abstract

The β1- and β2adrenoceptor agonist and thromboxane A2 (TXA2) antagonist properties of trimetoquinol (TMQ, I) and 1-benzyl substituted TMQ analogues [3′-iodo-4′,5′-dimethoxy TMQ, II; 3′, 5′-diiodo-4′-dimethoxy TMQ, III; 3′,4′-dimethoxy-5′ nitro TMQ, IV; 3′,4′-dimethoxy-5′-amino TMQ;V; and 3′,4′-dimethoxy TMQ, VI] were studied in guinea pig atria (β1) and trachea (β2), and in rat thoracic aorta and human platelets, respectively. The rank order of agonist activities in β1- and β2-adrenoceptor tissues was IV≥I>II>V>III>VI and I>II=IV=V>VI>III, respectively. An increase of β21-selectivity (2- to 3-fold) was observed for analogues V and VI as compared to TMQ. The rank order of inhibitory potency against U46619-induced contraction of rat aorta and human platelet aggregation and secretion was the same (I=II=III>IV>V>VI). The results show that varying the substituents at the 3′- and 5′-positions of the trimethoxybenzyl group of TMQ produces compounds which give different profiles of biological activity for β-adrenoceptor agonism versus TXA2 antagonism. Certain TMQ analogues, notably analogue V, showed a greater selectivity as β2-receptor agonists and TXA2 antagonists in vascular smooth muscle than the parent drug (TMQ), and the iodinated analogues (II and III) have promise as potential radioligands or photoaffinity probes for thromboxane A2 receptors.

Original languageEnglish (US)
Pages (from-to)21-31
Number of pages11
JournalEuropean Journal of Pharmacology
Volume184
Issue number1
DOIs
StatePublished - Aug 2 1990

Fingerprint

Tretoquinol
Prostaglandin H2 Receptors Thromboxane A2
Thromboxane Receptors
Thromboxane A2
Adrenergic Receptors
Pharmacology
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Trachea
Thoracic Aorta
Platelet Aggregation
Vascular Smooth Muscle
Aorta
Guinea Pigs
Blood Platelets
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Pharmacological evaluation of the β-adrenoceptor agonist and thromboxane receptor blocking properties of 1-benzyl substituted trimetoquinol analogues. / Shams, Gamal; Romstedt, Karl J.; Gerhardt, Mark A.; Harrold, Marc W.; Miller, Duane; Feller, Dennis R.

In: European Journal of Pharmacology, Vol. 184, No. 1, 02.08.1990, p. 21-31.

Research output: Contribution to journalArticle

Shams, Gamal ; Romstedt, Karl J. ; Gerhardt, Mark A. ; Harrold, Marc W. ; Miller, Duane ; Feller, Dennis R. / Pharmacological evaluation of the β-adrenoceptor agonist and thromboxane receptor blocking properties of 1-benzyl substituted trimetoquinol analogues. In: European Journal of Pharmacology. 1990 ; Vol. 184, No. 1. pp. 21-31.
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