Pharmacological activity of DC-015, a novel potent and selective α1-adrenoceptor antagonist

M. H. Yen, J. R. Sheu, I. H. Peng, Y. M. Lee, J. W. Chern

研究成果: 雜誌貢獻文章

31 引文 (Scopus)

摘要

The pharmacological activity of 3-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)-2,3-dihydroimidazo(1,2 -c)quinazolin-5(6H)-one (DC-015), a newly synthesized quinazoline derivative, was determined in rat isolated thoracic aorta and presser responses were determined in spontaneously hypertensive rats (SHR). Experimental results indicated that DC-015 is an α1-adrenoceptor-blocking agent in rat thoracic aorta as revealed by its competitive antagonism of phenylephrine-induced vasocontraction (pA2 = 10.54 ± 0.55). These effects still persisted in denuded aorta. It was as potent as prazosin pA2 = 10.04 ± 0.63). At higher concentrations (10 μM), DC-015 also expressed 5-hydroxytryptamine (5-HT) receptor competitive antagonism, but this 5-HT blocking effect was not found in the prazosin-administration group. [3H]Inositol monophosphate formation stimulated by phenylephrine (30 μM) in rat thoracic aorta was diminished by DC-015 (3 and 10 nM) and prazosin (10 nM); whereas the cAMP content of rat thoracic aorta was not altered by DC-015 and prazosin. Furthermore, intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1 mg kg-1) induced a dose-dependent reduction of mean arterial pressure which reached a maximal effect at 5 min after injection and persisted over 2 h in SHR. A higher dose of DC-015 (0.1 mg kg-1, i.v.) did not cause any significant changes in heart rate, whereas, the same dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease which seems to parallel the time course of the hypotensive response. We can conclude that the DC-015 is a potent, highly selective α1-adrenoceptor antagonist in vascular smooth muscle.

原文英語
頁(從 - 到)90-95
頁數6
期刊Journal of Pharmacy and Pharmacology
48
發行號1
出版狀態已發佈 - 1996
對外發佈Yes

指紋

Adrenergic Receptors
Prazosin
Pharmacology
Thoracic Aorta
Phenylephrine
Inbred SHR Rats
Quinazolines
DC 015
Serotonin Receptors
Inositol
Vascular Smooth Muscle
Intravenous Administration
Aorta
Serotonin
Arterial Pressure
Heart Rate
Injections

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

引用此文

Pharmacological activity of DC-015, a novel potent and selective α1-adrenoceptor antagonist. / Yen, M. H.; Sheu, J. R.; Peng, I. H.; Lee, Y. M.; Chern, J. W.

於: Journal of Pharmacy and Pharmacology, 卷 48, 編號 1, 1996, p. 90-95.

研究成果: 雜誌貢獻文章

Yen, M. H. ; Sheu, J. R. ; Peng, I. H. ; Lee, Y. M. ; Chern, J. W. / Pharmacological activity of DC-015, a novel potent and selective α1-adrenoceptor antagonist. 於: Journal of Pharmacy and Pharmacology. 1996 ; 卷 48, 編號 1. 頁 90-95.
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abstract = "The pharmacological activity of 3-((4-(2-methoxyphenyl)piperazin-1-yl)methyl)-2,3-dihydroimidazo(1,2 -c)quinazolin-5(6H)-one (DC-015), a newly synthesized quinazoline derivative, was determined in rat isolated thoracic aorta and presser responses were determined in spontaneously hypertensive rats (SHR). Experimental results indicated that DC-015 is an α1-adrenoceptor-blocking agent in rat thoracic aorta as revealed by its competitive antagonism of phenylephrine-induced vasocontraction (pA2 = 10.54 ± 0.55). These effects still persisted in denuded aorta. It was as potent as prazosin pA2 = 10.04 ± 0.63). At higher concentrations (10 μM), DC-015 also expressed 5-hydroxytryptamine (5-HT) receptor competitive antagonism, but this 5-HT blocking effect was not found in the prazosin-administration group. [3H]Inositol monophosphate formation stimulated by phenylephrine (30 μM) in rat thoracic aorta was diminished by DC-015 (3 and 10 nM) and prazosin (10 nM); whereas the cAMP content of rat thoracic aorta was not altered by DC-015 and prazosin. Furthermore, intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1 mg kg-1) induced a dose-dependent reduction of mean arterial pressure which reached a maximal effect at 5 min after injection and persisted over 2 h in SHR. A higher dose of DC-015 (0.1 mg kg-1, i.v.) did not cause any significant changes in heart rate, whereas, the same dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease which seems to parallel the time course of the hypotensive response. We can conclude that the DC-015 is a potent, highly selective α1-adrenoceptor antagonist in vascular smooth muscle.",
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AU - Chern, J. W.

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