| Vascular and cardiac effects of DV-7028, a selective, 5-HT2-receptor antagonist in rats. | |
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MedLine Citation:
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PMID: 9700989 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effect of 5HT2A-receptor antagonist DV-7028 (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6,7,8,9-tetrahydro - 2H-pyrido[1,2,-a]-1,3,5-triazine-2,4(3H)-dione maleate on the rat cardiovascular system was evaluated. DV-7028 (0.1 and 1.0 mg/kg), given intravenously, caused a significant, dose-dependent decrease in mean arterial blood pressure in anesthetized normotensive rats. In vagotomized rats, administration of DV-7028 resulted in a reduction of mean blood pressure, but this effect was less prominent than that seen in nonvagotomized rats. Intravenous administration of DV-7028 induced bradycardia, which was almost completely abolished by vagotomy. In pithed rats, bradycardia and hypotension were not demonstrated after DV-7028 administration. In pithed rats, serotonin administered intravenously caused a dose-dependent increase in blood pressure. In this experimental model, DV-7028 inhibited the pressor effects of serotonin at doses of 0.01 and 0.1 mg/kg, which caused neither hypotension nor bradycardia in anesthetized rats. DV-7028 strongly inhibited the pressor effects of serotonin in the isolated perfused hindlegs of the rat (IC50 = 0.032 +/- 0.004 microM) and caused a concentration-dependent, almost parallel shift to the right of the concentration-response curve to serotonin for its pressor effect in the rat perfused tail artery (pA2 value for DV-7028 was 7.92, a slope 0.94). These data demonstrate that DV-7028 exhibits 5-HT2A-receptor antagonistic property in the rat cardiovascular system. Besides this peripheral action, DV-7028, when applied in high doses, exerts hypotension and bradycardia via an unknown site and mechanism. |
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Authors:
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D Pawlak; M Adamkiewicz; J Malyszko; A Takada; M Mysliwiec; W Buczko |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cardiovascular pharmacology Volume: 32 ISSN: 0160-2446 ISO Abbreviation: J. Cardiovasc. Pharmacol. Publication Date: 1998 Aug |
Date Detail:
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Created Date: 1998-10-14 Completed Date: 1998-10-14 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7902492 Medline TA: J Cardiovasc Pharmacol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 266-73 Citation Subset: IM |
Affiliation:
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Department of Pharmacodynamics, University School of Medicine, Bialastrokystok, Poland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Baroreflex / drug effects Blood Pressure / drug effects Cardiovascular System / drug effects* Coronary Circulation / drug effects Heart / drug effects* Heart Rate / drug effects Hindlimb / drug effects, physiology Injections, Intravenous Ketanserin / pharmacology Male Piperidines / pharmacology* Rats Rats, Wistar Receptor, Serotonin, 5-HT2A Receptors, Serotonin / drug effects* Ritanserin / pharmacology Serotonin Antagonists / pharmacology* Triazines / pharmacology* Vagotomy |
| Chemical | |
Reg. No./Substance:
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0/Piperidines; 0/Receptor, Serotonin, 5-HT2A; 0/Receptors, Serotonin; 0/Serotonin Antagonists; 0/Triazines; 133364-63-3/DV 7028; 74050-98-9/Ketanserin; 87051-43-2/Ritanserin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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