The Effect of Fenoldopam on the Blood Pressure of the Rat |
| |
| Institution: | 1. Comparative Biology and Safety Sciences, Amgen, Thousand Oaks, CA 91320, USA;2. Eli Lilly and Company, Indianapolis, IN 46285, USA;3. Safety Assessment, Genentech, South San Francisco, CA 92056, USA;4. Drug Safety Research and Development, Pfizer, Groton, CT 06340, USA;5. Drug Safety Research and Development, Pfizer, Cambridge, MA 02139, USA;6. IQ Consortium, Washington, DC 20005, USA;7. Preclinical Safety, Sanofi, Bridgewater, NJ 08807, USA;8. GlaxoSmithKline, King of Prussia, PA 19406, USA;9. Nonclinical Development Sciences, Blueprint Medicines, Cambridge, MA 02139, USA;1. Medicinal Safety Research Laboratories, Daiichi Sankyo Co., Ltd., Tokyo, Japan;2. Japan Pharmaceutical Manufacturers Association Drug Evaluation Committee, Non-Clinical Evaluation Expert Committee, TF2, Japan;3. Consortium for Safety Assessment using Human iPS Cells (CSAHi): HEART team, Japan;4. Discovery Research Labs., Nippon Shinyaku Co., Ltd., Kyoto, Japan;5. Safety Research Department, ASKA Pharmaceutical Co., Ltd., Kanagawa, Japan;6. Safety Research Laboratories, Ono Pharmaceutical Co., Ltd., Fukui, Japan;7. Drug Safety Research Laboratories, Astellas Pharma Inc., Osaka, Japan;8. Discovery Research, Mochida Pharmaceutical Co., Ltd., Shizuoka, Japan;9. Preclinical Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan;10. Pharmacokinetics and Non-Clinical Safety Dept., Nippon Boehringer Ingelheim Co., Ltd., Hyogo, Japan;11. Biopharmaceutical Assessments Core Function Unit Medicine Development Center Eisai Co., Ltd., Eisai Co., Ltd., Ibaraki, Japan;1. Division of Applied Regulatory Science, Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA;2. Vertex Pharmaceuticals (Europe) Ltd, Abingdon, Oxfordshire, UK;3. Cyprotex US, LLC, Watertown, MA, USA;4. AbbVie Inc, North Chicago, IL, USA;5. Bristol-Myers Squibb, Princeton, NJ, USA;6. Division of Cardiology and Nephrology, Office of Cardiology, Hematology, Endocrinology and Nephrology, Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA |
| |
| Abstract: | - 1.Fenoldopam mesylate, a benzazepine derivative, is a D1 receptor agonist that lowers blood pressure through vasodilation of renal, mesenteric, coronary and cerebral vascular beds.
- 2.Experiments were performed in rats, and mean carotid blood pressure and heart rate were registered. Two series of experiments were performed: (1) fenoldopam as control group and (2) fenoldopam after pretreatment with one of the following drugs: the D1 antagonist SCH 23390, the D2 antagonist sulpiride, the selective β1-adrenergic antagonist atenolol, the selective β2-adrenergic antagonist ICI 118.551, the nonselective β-adrenergic antagonist propranolol and the neurotoxin that destroys catecholaminergic nerve terminals 6-hydroxydopamine (6-OH-DA).
- 3.Fenoldopam produced a dose-dependent hypotensive effect that was not modified by pretreatment of the rat with atenolol or propranolol; however, ICI 118.551 produced a significant reduction of the hypotensive response induced by fenoldopam.
- 4.Pretreatment of the animals with SCH 23390 produced a significant dose-related reversal of the rat blood pressure reduction induced by low doses of fenoldopam. Sulpiride produced a result similar to that induced by pretreatment with SCH 23390.
- 5.The pretreatment of the animals with 6-OH-DA surprisingly attenuated the response induced by fenoldopam and produced only a significant reversal of the reduction of mean blood pressure induced with the lower dose of fenoldopam.
- 6.The findings obtained in the present work do not provide further evidence of direct participation of β2-adrenergic receptors on the mechanism of action of fenoldopam. Its action seems to be mainly due to activation of D1 cardiovascular receptors.
|
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
