Possible involvement of central adrenergic and histaminergic systems in clonidine-induced inhibition of pinna reflex.

Clonidine produced dose-dependent inhibition of pinna reflex in rats, the ED50 being 1.20 +/- 0.28 mg/kg. The effect of agents affecting adrenergic, tryptaminergic and histaminergic systems were evaluated on clonidine-induced inhibition of pinna reflex. All these agents had no effect on pinna reflex. Phentolamine, phenoxybenzamine, prazosin, propranolol, haloperidol, cyproheptadine and mepyramine did not affect significantly the action of clonidine. However, reserpine, alpha-methyl-p-tyrosine, alpha-methyldopa, diethyldithiocarbamate, 6-hydroxydopamine, yohimbine and cimetidine significantly blocked clonidine-induced inhibition of pinna reflex, indicating the involvement of central adrenergic-histaminergic systems.

Effect of probucol on triton induced hyperlipidemias in CFY rats.

The two phases of triton test have been used to find out the effect of probucol to evaluate whether it is effective cholesterol lowering agent prophylactically or therapeutically. Probucol is shown to be a better accelerator for lipid clearance in triton hyperlipidemia than clofibrate. The clearance rate of VLDL is more than that of LDL. In the first phase of triton test probucol has more effect on cholesterol synthesis than triglycerides while in the second phase of triton test probucol has more effect as a clearing agent on triglycerides than on cholesterol.

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.

Acetic acid and phenylquinone writhing test: a critical study in mice.

Studies were planned to establish the dose-effect relationship with both acetic acid and phenylquinone and to find out suitable concentrations for these two chemicals for pre- and post screening. The LD50 of acetic acid and phenylquinone were found to be 3.16% and 0.23%, respectively. Based on the studies conducted, the prescreening and postscreening concentrations of 0.5% is recommended for acetic acid, while for phenylquinone, prescreening concentration of 0.005% and postscreening concentration of 0.02% is advocated. Using this criterion in the acetic acid writhing test, analgin was the most potent analgesic while aspirin was the least. However, suprofen was most potent and paracetamol least among analgesics employed against phenylquinone induced writhing.

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.

Synthesis and biological activity of some new furan quaternary salts.

A series of new N-(5-substituted 2-furfuryl)-N,N-dimethyl-N-aryloxyalkyl quaternary ammonium salts relating to general structure IV has been synthesized by reacting 5-substituted 2-(N,N-dimethylaminomethyl)furans IIa-d with appropriate aryloxyalkyl bromides III. The resulting compounds are tested for in vitro antimicrobial activity. A simpler synthesis of 5-nitro-2-(N,N-dimethylaminomethyl)furan (IId) involving the reduction of N,N-dimethyl-5-nitro-2-furamide (Ib) with diborane is described. A new compound, 5-bromo-2-(N,N-dimethylaminomethyl)furnan (IIc), is prepared in a similar way. Many of these compounds (22, 28, 34, 37-42, 44, and 45) indicate high activity against Staphylococcus aureus, Streptococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa and are more active than nitrofurantoin, Compounds 22, 34 and 41 exhibit the highest in vitro antibacterial activity in the series. Some of these quaternary salts (22, 25, 37, 37-41, and 60) possess appreciable activity against Mycobacterium tuberculosis H37Rv. None of these compounds show significant antifungal activity. Eight compounds (18, 21, 22, 26-28, 32, and 34) have high in vitro antibacterial activity were inactive when tested for anthelmintic activity in rats against Nippostrongylus brasiliensis and Hymenolepis nana.

Antimicrobial agents: synthesis and antimicrobial activity of new aryloxyalkyl esters of p-hydroxybenzoic acid.

Several new aryloxyalkyl esters of p-hydroxybenzoic acid were synthesized and screened for in vitro antimicrobial activity. Although a few compounds showed low antifungal activity, many possessed appreciable in vitro antibacterial activity. However, none of these compounds was active against Mycobacterium tuberculosis (H37Rv).