Drugs online research references
J Cardiovasc Pharmacol. 1989;13 Suppl 2:S1-4; discussion S4.
Effect of doxazosin on cholesterol synthesis in cell culture.
D'Eletto RD, Javitt NB.
Division of Hepatic Diseases, New York University Medical Center, New York 10016.
The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2471008&dopt=Abstract
Zhongguo Yao Li Xue Bao. 1999 May;20(5):431-4.
Selective effects of alfuzosin and doxazosin with intraduodenal administration on urethral pressure of cats.
Yang ZH, Ren LM, Wu ZJ, Fu SX, Li YS.
Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
AIM: To observe the selective effects of alfuzosin (Alf) and doxazosin (Dox) on the urethral pressure by different administration routes. METHODS: The urethral pressure of the anesthetized cat was increased by electric stimulation of the hypogastric nerve. The different effects of Alf or Dox on the arterial blood pressure and urethral pressure between intraduodenal administration (i.d.) and intravenous infusion (i.v.) were compared. RESULTS: When the hypogastric nerve was stimulated by electric stimulation (10 Hz, 25 V), the ratios of ED20(BP)/ED50(UP) i.d. to ED20(BP)/ED50(UP) i.v. were 10.9:4.3 for Alf, and 3.1:2.1 for Dox. The reduction in urethral pressure induced by i.d. Alf was greater than that by i.v. Alf. Dox did not show any difference in its effects by 2 administration routes. CONCLUSION: Intraduodenal administration of Alf, but not Dox, selectively decreased the urethral pressure elevated by electric stimulation. The uroselectivity of i.d. Alf was not due to the species difference in its bioavailability and biotransformation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10678091&dopt=Abstract
J Cardiovasc Pharmacol. 1989;13 Suppl 2:S11-8; discussion S18-9.
Effects of doxazosin and other antihypertensives on serum lipid levels and lipoprotein lipase in the C57BR/cdJ mouse.
Krupp MN, Hoover KW, Valentine JJ.
Central Research Division, Pfizer Inc., Groton, Connecticut.
Doxazosin has been shown to lower serum cholesterol levels in the cholesterol-fed (0.75% in a synthetic diet that contains sucrose and cholic acid) C57BR/cdJ mouse. These studies show that the drug's main effect is to lower low-density lipoprotein (LDL) cholesterol and leave high-density lipoprotein (HDL) cholesterol levels unchanged. The drug had cholesterol-lowering effects in this model at doses down to 3 mg/kg. In order to determine if these effects are unique to selective alpha 1-inhibitors, other antihypertensives including hydralazine, papaverine, and captopril were investigated. None of the drugs has any effects on the plasma lipid metabolite levels. The effects of propranolol and polythiazide on plasma lipid levels were also examined in these mice. Propranolol had no effect, whereas the diuretic increased plasma cholesterol levels. Both propranolol and polythiazide increased plasma triglycerides. Doxazosin has been shown to inhibit cGMP phosphodiesterase in the laboratory. The effects of zaprinast, a cGMP phosphodiesterase inhibitor, were tested in order to determine if this property of the drug could be responsible for its lipid-lowering activity. The data show that there are no effects on plasma lipids in zaprinast-treated animals. Doxazosin treatment increased heparin-releasable lipoprotein lipase in fasted chow-fed mice. The drug was without effect on the activity of hepatic lipase present in the plasma after heparin release. No effects were observed on the tissue levels of either hepatic or lipoprotein lipases (heart or adipose tissue).
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2471010&dopt=Abstract
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