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Biomedical subjects

R Kaushal

Publications and source records attributed to R Kaushal.

28 records · Page 2Linked to original sources

Polysorbate 80: a pharmacological study.

Polyoxyethylene (20) sorbitan monooleate (polysorbate 80, Tween 80), a surfactant, has been widely used as a solvent for pharmacological experiments. In the present study, polysorbate 80 was found to have toxicity of a low order in both the mice and rats when given by i.p. and p.o. routes. It produced mild to moderate depression of the central nervous system with a marked reduction in locomotor activity and rectal temperature, exhibited ataxia and paralytic activity and potentiated the pentobarbital sleeping time. On intravenous administration in dogs, it had a dose-dependent hypotensive effect. Polysorbate 80 did not have a direct stimulant or relaxant effect on either guinea pig ileum or rat uterus, however, it antagonised the contractions induced by acetylcholine, histamine, barium, 5-hydroxytryptamine and carbachol in a dose-dependent manner. A direct relaxant effect was observed on rabbit jejunum. A dose-dependent myocardial depressant effect was observed on guinea pig and rabbit paired atrial preparations. On the electrically-driven guinea pig left atrial preparation, polysorbate 80 exhibited a dose-dependent negative inotropic action. Polysorbate 80 did not induce diuresis in rats upto a dose of 2.5 ml/kg. The results of the present study indicate that polysorbate 80 can neither be used as a solvent for isolated tissue experiments nor when considered for intravenous administration. However, polysorbate 80 can be employed safely as a vehicle for neuropsychopharmacological experiments in doses not exceeding 1 ml/kg.

Animals↗

A pharmacological study of propane-1,2-diol.

Propane-1,2-diol (propylene glycol, PG), considered to be a safe solvent and commonly used as a vehicle in pharmacological and toxicological investigations, showed various neuropsychopharmacological activity in albino mice and rats. In lower concentrations (10-20%), at dose level of 10 ml/kg, PG did not show any significant neuropsychopharmacological activity either by i.p. or p.o. routes. But higher concentrations (50-100%), at same dose level by i.p. route, were found to have moderate to marked effect. There was decrease in locomotor activity, body and limb tone, respiration, rectal temperature and suppression of secondary conditioned responses. Significant potentiation of pentobarbitone (pentobarbital) hypnosis, slight increase in d-amphetamine toxicity in aggregated mice and pronounced analgesic and anti-inflammatory activity were also observed. Most of the above effects were also observed on p.o. treatment but the effects were of lesser degree. PG did not produce any effect on dog or cat blood pressure up to 100% concentration at the dose level 0.5 ml/kg. However, it potentiated the adrenaline (epinephrine) and noradrenaline (norepinephrine) response. On isolated smooth muscle preparations, in 50-100% concentrations, a dose-dependent non-specific blockade was observed against agonists viz. acetylcholine, histamine, 5-HT and barium chloride. No effect was seen on cardiac tissue preparation. On the basis of present findings, it is suggested that propylene glycol as a solvent be used only in low concentration of not more than 10% for pharmacological and toxicological investigations.

Analgesics↗

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↗

Protective effect of ST-93 against ouabain induced arrhythmias in guinea pigs.

ST-93, a clonidine analog was studied for its antiarrhythmic activity in anaesthetised guinea pigs against ouabain induced arrhythmia. The amount of ouabain required (micrograms/kg) for the production of ventricular premature best. Ventricular fibrillation and cardiac arrest was recorded in control and drug treated group of animals. Both ST-93 and clonidine produced significant antiarrhythmic effect in guinea pigs. This protective effect was significantly blocked by yohimbine, suggesting that the antiarrhythmic effect is mediated through presynaptic alpha 2-adrenoceptors.

Animals↗

Neuropharmacological actions of some newly synthesized Mannich bases.

Benzamido (alkyl) methyl pyrrolidine Mannich bases were synthetized and subjected to certain neuropharmacological studies. All the bases reduced the pentobarbitone sleeping time and rota-rod grip of rats. The Mannich bases II, III and V raised the minimal electro-shock seizure threshold of rats. The TAB-induced pyrexia was not reduced by the bases I and III in rabbits. None of the bases showed any significant analgesic activity.

Amines↗