ABSTRACT
1. The effects of tulobuterol on the atrial rate was compared with those of isoproterenol, pindolol and propranolol in spontaneously beating isolated right atria of the rat. 2. Isoproterenol markedly increased atrial rate. To the contrary, propranolol, pindolol and tulobuterol decreased atrial frequency. The chronotropic effect of tulobuterol was similar to that of pindolol but lower than that of propranolol. 3. Interactions between tulobuterol and isoproterenol showed that tulobuterol potentiated the chronotropic effect of low concentrations of isoproterenol but reduced the positive chronotropic response to higher concentrations of isoproterenol. 4. These results suggest that tulobuterol is a partial agonist on atrial beta-receptor but also seems to have another action (possibly a membrane stabilizing activity) which reduced the originally induced effect on beta-receptors as a non-competitive antagonist.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Terbutaline/analogs & derivatives , Animals , Cell Membrane/drug effects , Female , Heart/drug effects , Heart Rate/drug effects , In Vitro Techniques , Isoproterenol/pharmacology , Male , Myocardium/metabolism , Pindolol/pharmacology , Propranolol/pharmacology , Rats , Rats, Inbred Strains , Terbutaline/pharmacologyABSTRACT
There is a pharmacokinetic interaction between digoxin and diazepam that increases the elimination half-life of digoxin. It may be due to a reduction of digoxin tissue concentrations and to an enhanced effect of diazepam on digoxin binding to plasma albumin. Diazepam (10(-5) M) also induces a positive inotropic effect in guinea-pig isolated atria. In a study of a possible pharmacodynamic interaction between both drugs, the inotropic response to digoxin has been examined in rat isolated atria in the presence of diazepam. The atria were kept in Tyrode at 37 degrees C, bubbled with 95% O2 and 5% CO2 and electrically stimulated at twice the threshold voltage. The results indicate that diazepam induces an inotropic effect at 10(-5) M (P less than 0.05) and reduces (P less than 0.05) at 10(-9), 10(-7) and 10(-5) M the inotropic response to digoxin (10(-5) M).
Subject(s)
Diazepam/pharmacology , Digoxin/pharmacology , Myocardial Contraction/drug effects , Animals , Digoxin/antagonists & inhibitors , Digoxin/metabolism , Electric Stimulation , Female , Half-Life , In Vitro Techniques , Male , Rats , Rats, Inbred Strains , Stimulation, ChemicalABSTRACT
The opioid-receptor antagonist naloxone was administered intravenously in a 0.8-mg bolus to five healthy volunteers, aged 21 to 31, in a double-blind study designed to investigate the effect of endogenous opioids on blood pressure, heart rate, and urinary excretion of catecholamines in healthy adults. Three hours after administration of naloxone there were significant increases in systolic blood pressure (P less than 0.001) and heart rate (P less than 0.05). The amount of epinephrine excreted in urine during the four hours after administration of naloxone or placebo was significantly higher (P less than 0.05) in subjects given naloxone. These effects support the hypothesis that an endogenous opioid system is involved in the regulation of systolic blood pressure and heart rate in healthy adults. The results also indicate that adrenally released epinephrine could mediate the cardiovascular effect of endogenous opioids.
Subject(s)
Epinephrine/physiology , Hemodynamics/drug effects , Naloxone/pharmacology , Adult , Blood Pressure/drug effects , Catecholamines/urine , Epinephrine/urine , Heart Rate/drug effects , Humans , Injections, Intravenous , Male , Norepinephrine/urine , Time FactorsABSTRACT
The protective effect of phenytoin against an electroshock lethal dose (ELD), was compared with that of three different beta-blocking agents. These compounds were propranolol with quinidine-like activity (QLA) but no intrinsic sympathomimetic activity (ISA), practolol with ISA but no QLA and metoprolol with no ISA but some QLA. Phenytoin (15 mg/kg) and propranolol (70 mg/kg) protected all the animals. Metoprolol was only effective at higher concentrations (130 mg/kg). Practolol afforded some degree of protection at low doses (20 mg/kg) but at higher doses its ISA can be deleterious by decreasing the ELD threshold. These results suggest that QLA is more important than beta-blocking activity for protection against electroshock lethality.
