PubMed Health⌕ Search

Biomedical subjects

R K Varma

Publications and source records attributed to R K Varma.

32 records · Page 2Linked to original sources
PubMedDate not supplied

Effect of flutonidine on ouabain-induced arrhythmias and lethality in guinea-pig.

Flutonidine (10, 20 and 40 micrograms/kg) was studied for its efficacy against the cardiotoxic effects induced by slow intravenous infusion of ouabain in guinea-pigs. Flutonidine increased the dose of ouabain required to cause ventricular premature beats, ventricular tachyarrhythmias and lethality. Flutonidine further inhibited the rate of ouabain-induced rise in blood pressure. Alpha 1 adrenoceptor antagonist, corynanthine (1 mg/kg), could not alter the protective action of flutonidine; whereas idazoxan (100 micrograms/kg), the alpha 2 adrenoceptor blocker, showed significant inhibition of this effect. It is suggested that the reduction in the arrhythmogenic and lethal effects of ouabain by flutonidine may be due to its ability to reduce sympathetic tone by interfering with the neural components of ouabain action mediated through alpha 2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

St-93 hyperglycemia in Wistar rats.

The alpha 2-adrenoceptor agonist St-93 was evaluated for its effect on blood glucose levels in Wistar rats. A dose-dependent increase in blood glucose was observed in rats after intraperitoneal administration of St-93. The hyperglycemic effect of St-93 was not altered by prazosin and propranolol, whereas idazoxan significantly inhibited this effect. Pretreatment with reserpine did not affect the hyperglycemic effect of St-93. There was no significant increase in the blood glucose values with St-93 in streptozotocin-diabetic rats. It may be concluded that the hyperglycemia induced by St-93 is mediated through alpha 2-adrenoceptors, possibly located on pancreatic beta-cells.

Animals↗
PubMedDate not supplied

Effect of various hypotensive agents on locomotor activity and blood pressure of rats.

The effect of various hypotensive agents were simultaneously tested on locomotor activity and blood pressure of unanaesthetised (conscious) rats. The agents viz clonidine, prazosin, furosemide and hexamethonium were found to reduce significantly the locomotor activity as well as blood pressure, 30 min post administration. Phenoxybenzamine and alpha-methyldopa produced similar type of effect but after 60 and 120 min post administration respectively. Aminophylline and propranolol failed to reduce locomotor activity as well as blood pressure, 60 and 90 min post administration. The findings of the present study are strongly indicative that hypotensive agents reduce locomotor activity and that the reduction is sequel to the fall in blood pressure.

Animals↗
PubMedDate not supplied

Biotransformation of tipredane, a novel topical steroid, in mouse, rat, and human liver homogenates.

The in vitro biotransformation pathways of 3H-tipredane (3H-TP) were studied. 3H-TP, at concentrations of 1 and 250 microM, was incubated with the 10,000g supernatant fraction of the liver homogenates of mice, rats, and one human. The incubation mixtures were deproteinated with methanol and, after removal of methanol by evaporation, extracted with dichloromethane. The dichloromethane extracts were then fractionated by HPLC. 3H-TP was extensively biotransformed by the liver homogenates of the three species studied; 17 metabolites were isolated and characterized by their retention times on HPLC compared to those of the reference standards. Fourteen metabolites were identified using MS and, for some, NMR spectroscopy. Three major biotransformation pathways of TP were identified: 1) sulfoxidation, 2) elimination of the alkylthio groups, and 3) hydroxylation of the steroid nucleus. Combinations of these processes and subsequent reactions resulted in the formation of numerous metabolites whose biological activities were significantly less than that of TP. The separation of local anti-inflammatory activity from systemic side effects observed for TP in animals and humans is most probably due to its metabolic inactivation, primarily in the liver.

Administration, Topical↗
PubMedDate not supplied

Solvent artifacts likely to be induced by dimethylformamide.

Dimethylformamide (DMF) is widely used as a drug solvent. We found DMF to have wide-spread pharmacological effects including depressant effect on CNS evidenced by a decrease in locomotor activity, body and limb tone and rectal temperature, and potentiation of pentobarbitone sleep. A dose-dependent hypotensive effect was seen in cats and rats. In rats, it was partially blocked by atropine and was associated with bradycardia. DMF antagonised the contractions of smooth muscle induced by many agonists. An atropine sensitive spasmogenic effect was observed on rabbit ileum at 20 ml/l and a direct relaxant effect at 50 ml/l. A positive inotropic effect on guinea pig atria was observed with 5 ml/l. The results indicate DMF concentrations that may not perhaps produce 'solvent artifacts' when used as a solvent.

Animals↗