Drugs online research references
J Cardiovasc Pharmacol. 1989;13 Suppl 2:S20-4; discussion S24.
Interactions of doxazosin with insulin or glucagon in the ob/ob mouse.
Swindell AC, Valentine JJ.
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Doxazosin, a selective inhibitor of alpha 1-adrenergic receptors, when administered alone or in combination with insulin or glucagon to mature ob/ob mice, consistently lowered levels of triglycerides, cholesterol, glycerol, and lactate and increased levels of beta-hydroxybutyrate and glucose. Doxazosin suppressed the tendency of insulin to elevate triglycerides but had no effect on the hypoglycemic response to insulin. Doxazosin and insulin together (but neither alone) lowered free fatty acids (FFA). Glucagon lowered cholesterol and raised glucose but did not affect triglycerides or beta-hydroxybutyrate. Analysis of variance indicates that a simple additive-effects model cannot explain the interactions between doxazosin and insulin on triglycerides, glucose, and FFA. It is suggested that the alpha 1-adrenergic system may contribute to glycemic control and to ambient hypercholesterolemia, especially in the presence of insulin resistance, as in ob/ob mice, and that the hypolipidemic response to alpha 1-adrenergic inhibition may involve insulin pathways.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2471011&dopt=Abstract
J Cardiovasc Pharmacol. 1989;13 Suppl 2:S25-9; discussion S29-30.
Serum lipids, lipoproteins, hemodynamics, and hemostasis in doxazosin-treated monkeys.
Karge WH 3rd, Kowala MC, Weiner EJ, Nicolosi RJ.
Department of Clinical Scieces, University of Lowell, Massachusetts 01854.
The effect of doxazosin administration on hemodynamics, hemostasis, and serum lipid and lipoprotein levels was investigated in cynomolgus monkeys (Macaca fascicularis) with diet-induced hypercholesterolemia. Acute administration of doxazosin (1 and 5 mg/kg) reduced resting mean arterial pressure by 20% without affecting heart rate, and completely inhibited the pressor response to phenylephrine. Platelet aggregation, prothrombin time, and activated partial thromboplastin time were not altered by the drug. Long-term doxazosin administration (1, 10, and 20 mg/kg/day) was associated with significant reductions in levels of total serum cholesterol (13%), very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol (14%), and apolipoprotein B (15%) without any significant effects on high-density lipoprotein (HDL) cholesterol and apolipoprotein A-1. A 76% reduction in serum triglycerides, independent of drug level, was also seen in doxazosin-treated monkeys. In monkeys removed from drug treatment, serum cholesterol initially exceeded and then returned to pretreatment levels, whereas serum triglycerides remained low for 3 weeks. In our hypercholesterolemic monkey model, the administration of doxazosin resulted in beneficial changes in lipid and apolipoprotein profiles, hemostasis, and hemodynamics.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2471012&dopt=Abstract
J Cardiovasc Pharmacol. 1989;13 Suppl 2:S31-6; discussions 36-7.
Influence of doxazosin on lipid transport in rats and hamsters.
Ontko JA, Woodside WF.
Department of Biochemistry and Molecular Biology, University of Oklahoma College of Medicine, Oklahoma City.
A variety of nutritional conditions were investigated to identify those most responsive in terms of selective alpha 1-adrenergic inhibition (alpha 1-inhibition) on the serum lipid concentrations in rats and hamsters. In rats fasted for 24 h and then refed a lipogenic diet for the same period, serum triglycerides were markedly elevated. Inclusion of the selective alpha 1-adrenergic inhibitor (alpha 1-inhibitor) doxazosin in the diet decreased the intensity of this response. Serum cholesterol was not appreciably altered by the drug in these animals. Although dietary doxazosin did not affect serum lipids in rats fed chow ad libitum, in chow-fed hamsters (which have much higher serum lipid levels than rats) consumption of the drug for 4 days substantially decreased serum levels of both triglyceride and cholesterol. Very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were all decreased by doxazosin. It is suggested that selective alpha 1-inhibition influences lipoprotein metabolism at several sites, including both formation and removal processes. The hamster may be especially useful in studies designed to define these sites and the underlying mechanisms involved.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2471013&dopt=Abstract
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