bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verapamil and nifedipine effects on gastric acid secretion and ulcer formation in rats
Authors: Glavin Gary B 
Published: April 2011

Abstract
The calcium channel antagonists verapamil and nifedipine were examined for their effects on conscious basal gastric acid output, stress ulcer formation and on ethanol-induced ulcers. Both compounds significantly reduced gastric acid secretion, however verapamil did so in a dose-related manner. Both verapamil and nifedipine significantly attenuated stress gastric ulcer formation. Nifedipine, at a dose of 32.0 mg kg−1, virtually abolished stress ulcers. Verapamil exacerbated, while nifedipine, at 32.0 mg kg−1, attenuated ethanol-induced gastric ulcers. The differential gastrointestinal effects of these calcium channel antagonists support the existence of multiple classes of calcium channels in the gut and suggest an important role for intracellular calcium and hence, its blockade, in gastric pathophysiology.
Brain monoamines during carrageenan-induced acute paw inflammation in rats
Authors: Bhattacharya S K , Das Neeta , Rao P J R Mohan 
Published: April 2011

Abstract
Paw inflammation was induced in rats by sub-plantar administration of carrageenan. Significant inflammatory oedema was observed 1 h later and the peak effect was noted between 3–4 h. The oedema was markedly reduced after 12–24 h. Steady state levels of whole brain and hypothalamic monoamines were estimated spectrofluorometrically during the course of the carrageenan-induced paw inflammation. In addition, the rate of accumulation of the brain 5-hydroxytryptamine (5-HT) and noradrenaline (NA) was assessed in clorgyline-pretreated rats during the inflammation. The whole brain and hypothalamic concentrations of 5-HT and NA were augmented during the early phase of the inflammation, but fell below control values when peak inflammation was achieved. Thereafter, the monoamine levels tended to normalize by 24 h when the inflammation had virtually subsided. On the contrary, whole brain and hypothalamic dopamine levels remained largely unaffected. The rate of accumulation of brain 5-HT and NA were enhanced during carrageenan inflammation, indicating that the turnover of these monoamines is augmented during the inflammatory process. The results suggest that acute peripheral inflammation may significantly affect central 5-HT and noradrenergic activity in rats.
Dopamine-mediated behaviour following chronic treatment with B-HT 920
Authors: Darmani N A , Sewell R D E , Nicholls P J 
Published: April 2011

Abstract
Following subchronic (5-day) dosing with B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo(4,5-d)azepine (1 mg kg−1 day−1 i.p.) in rats there was a significant increase in both apomorphine-induced motor activity and stereotypy. On continued B-HT 920 treatment, however, the enhancement of apomorphine motor activity faded into insignificance but the increase in stereotypy persisted beyond 15 days. The results are discussed in terms of dopamine autoreceptor tolerance, postsynaptic D2 supersensitivity and possible differential effects in different brain loci on the above two receptor sub-classes.
Theophylline Metabolism by Human, Rabbit and Rat Liver Microsomes and by Purified Forms of Cytochrome P450
Authors: McManus M E , Miners J O , Gregor D , Stupans I , Birkett D J 
Published: April 2011

Abstract
The capacity of human, rabbit and rat liver microsomes and purified isozymes of cytochrome P450 to metabolize theophylline has been assessed. In all three species the 8-hydroxylation of theophylline to 1,3-dimethyluric acid (1,3-DMU) was the major pathway. In human, control rabbit and rat liver microsomes this metabolite accounted for 59, 77 and 94%, respectively, of the total metabolites formed. In both human and control rabbit liver microsomes the N-demethylation of theophylline to 1-methylxanthine (1-MX) accounted for 20% of the total metabolites formed. N-demethylation of theophylline to 3-methylxanthine (3-MX) accounted for 21% of theophylline metabolism in human microsomes but was a minor pathway in control rabbit and rat microsomes. Acetone and phenobarbitone pretreatment markedly increased the formation of 1,3-DMU by rabbit liver microsomes. Rifampicin and 2,3,7,8-tetrachlorodi-benzo-p-dioxin (TCDD) administration caused a slight but significant increase in this pathway. In general the N-demethylation pathways in rabbit liver microsomes were refractory to induction. In the rat, the metabolism of theophylline to 1-MX, 3-MX and 1,3-DMU were all significantly increased in Aroclor 1254, dexamethasone, phenobarbitone and 3-methylcholanthrene-treated microsomes. In reconstitution experiments the polycyclic hydrocarbon inducible rabbit cytochrome P450 Forms 4 and 6 and the constitutive Form 3b all metabolized theophylline to its three metabolites. In human liver microsomes from four subjects anti-rabbit cytochrome P450 Form 4 IgG inhibited the metabolism of theophylline to 1-MX, 3-MX and 1,3-DMU by approximately 30%. These data indicate that theophylline is metabolized by multiple forms of cytochrome P450 in human, rabbit and rat liver microsomes.
The Effect of Varying Percentages of Haemodilution with Fluosol-DA or Normal Saline on Antipyrine Metabolism in the Rat
Authors: Shrewsbury Robert P , Oliver Sharon R , Anderson Wanda T , Lewis Lee M , White Lisa G 
Published: April 2011

Abstract
Antipyrine disposition and metabolism in conscious, unrestrained rats after 25 or 50% haemodilution with Fluosol or normal (0.9% NaCl) saline is reported. Rats received an intravenous antipyrine dose (20 mg kg−1) 0.5, 24, 48, or 72 h after haemodilution and its pharmacokinetic parameters have been compared with non-exchanged control animals. Haemodilution 25% with Fluosol initially depressed antipyrine metabolism for 24 h by decreasing the antipyrine urinary excretion rate constant and the formation rate constants of 4-hydroxyantipyrine (4-OH) and 3-hydroxymethylantipyrine (3-OHME). Metabolism was then increased for 48 and 72 h with a slight increase in all rate constants. Haemodilution 50% with Fluosol produced a similar pattern but with significant increases in the 3-OHME formation rate constant found at 48 and 72 h. Haemodilution 25% with saline reduced 4-OH formation for 48 h. Haemodilution 50% with saline significantly reduced antipyrine urinary excretion at all times. After a significant increase in the 4-OH and 3-OHME formation rate constants at 24 h following 50% haemodilution with saline, the rate constants were significantly decreased at 48 and 72 h. Haemodilution 25% with Fluosol significantly reduced the antipyrine Vd at 0.5 and 72 h. After haemodilution 50% with Fluosol, the Vd alternated between values greater and less than control throughout the 72 h. Haemodilution 25 or 50% with saline had little influence on Vd.
The role of adrenoceptors in the mechanism of reserpine-induced stimulation of gastric acid secretion in the rat
Authors: Salim Aws S 
Published: April 2011

Abstract
The role of α- and β-adrenoceptors in the mechanism of reserpine-induced stimulation of gastric acid secretion in the rat has been examined. After 6 h reserpine (0.1 mg kg−1 i.p.) significantly stimulated acid secretion relative to control values (176 ± 4 vs 60 ± 3 μmol, mean ± s.e.m., n = 10, P &lt; 0.001). Neither coeliac ganglionectomy nor propranolol (5–15 mg kg−1) influenced this action. Vagotomy prevented acid stimulation by reserpine and was associated with H+ output similar to that of vagotomy controls (13 ± 1 vs 14 ± 1 μmol, mean ± s.e.m., n = 10). Dose-dependent inhibition of the reserpine-induced acid secretion was produced by phenoxybenzamine or phentolamine; an inhibition similar to that achieved by vagotomy was noted with the 15 mg kg−1 dose (13 ± 1 and 15 ± 1 μmol, respectively, vs 176 ± 4 μmol, mean ± s.e.m., n = 10, P &lt; 0.001). The similarity in action between vagotomy and large doses of phenoxybenzamine or phentolamine suggests that, in the rat, vagal α-adrenoceptor stimulation is directly involved in the mechanism of reserpine-induced stimulation of gastric acid secretion.
Thermal Studies on the Interaction of Water and Microcrystalline Cellulose
Authors: Fielden K E , Newton J M , O'Brien P , Rowe R C 
Published: April 2011

Abstract
The interaction between water and microcrystalline cellulose in the absence and presence of lactose has been studied by thermogravimetric analysis, differential thermal analysis and immersional calorimetry. The results indicate that most of the water held within a system used for the preparation of spherical granules by extrusion/spheronization is present as free water which may be readily lost by evaporation. There is approximately 0.856 mol of water per 100 g of microcrystalline cellulose which appears to be absorbed as structured water. Microcrystalline cellulose may therefore be described as a ‘molecular sponge’. The enthalpy of fusion of the ‘free’ water offers a simple method of estimating the effective surface area of the microcrystalline cellulose.
A Method to study the Kinetics of Oral Mucosal Drug Absorption from Solutions
Authors: Tucker Ian G 
Published: April 2011

Abstract
A method has been developed which allows the kinetics of oral mucosal drug absorption from solutions to be studied in a single 15–20 min test. This is an improvement over the traditional buccal absorption test which requires a separate experiment for each time point, thus taking days for each kinetic profile. It should also allow for disappearance of drug from the mouth and appearance in the plasma to be monitored simultaneously. The drug solution includes 8 μg mL−1 phenol red as a marker for salivary secretion. Samples are withdrawn at suitable times with a positive displacement pipettor and analysed for drug and phenol red. Salivary volume time data are described by least squares polynomials. Kinetic parameters are estimated by non-linear least squares regression. The method, which requires that phenol red is not lost during a test, provides an internal test for this. It also requires that phenol red and the drug do not interfere with each other’s assay, that saliva does not affect the assays of these materials, and that phenol red does not interfere with the absorption of the drug.
Evidence that the kappa agonist U50488H has non-opioid actions
Authors: Hayes A G , Birch P P , Cavicchini E 
Published: April 2011

Abstract
The antagonism of the antinociceptive effects of various κ-opioid agonists has been studied in the mouse abdominal constriction test. Naloxone produced a much smaller degree of antagonism of U50488H than it did of two other κ-agonists, U69593 and tifluadom. The κ-selective antagonist, norbinaltorphimine, also failed to shift the dose-response curve to U50488H in this test, despite producing considerable antagonism of the U50488H effect in the rotarod test and of U69593 in both experimental situations. These results are suggestive of a non-opioid component to the action of U50488H in the abdominal constriction test. At high concentrations, U50488H, but not U69593, also showed non-opioid effects in reducing contractile activity in the field-stimulated isolated guinea-pig ileum, as demonstrated by the profile of antagonism seen with β-chlornaltrexamine and naloxone. These results suggest that U69593, rather than U50488H, may be the κ-agonist of choice to use, particularly in in-vivo experiments.
Increased vasodilator response to acetylcholine of renal blood vessels from diabetic rats
Authors: Bhardwaj R , Moore P K 
Published: April 2011

Abstract
The vasodilator effect of acetylcholine (ACh) and nitro-prusside and the vasoconstrictor effect of noradrenaline was assessed in the perfused kidney of streptozocin diabetic rats. Compared with control animals injected with acidified saline, the renal vasoconstrictor effect of noradrenaline was increased in diabetic rats both in terms of the dose required to produce 50% of the maximal effect (EC50) and in the maximal response achieved. The renal vasodilator effect of ACh (but not nitroprusside) was similarly enhanced in diabetic animals. The effect of ACh (but not nitroprusside) in the perfused kidney of both control and diabetic rats was reduced or abolished by mepacrine (10 μM), metyrapone (10 μM) or methylene blue (100 μM) suggesting that ACh exhibits vasodilator activity in the rat kidney by virtue of releasing endothelium derived relaxing factor (EDRF). These results are in contrast to previous published reports demonstrating reduced biosynthesis of EDRF in the aorta of diabetic rats. The mechanism which underlies the increased renal vascular response to ACh is not known. However, increased endothelial cell turnover or cholinoceptor number, elevated activity of enzyme(s) which synthesise EDRF or hyperresponsiveness of vascular smooth muscle to released EDRF should all be considered.
The Interaction of Papain with Polycations
Authors: Mekras C I , Lawton J B , Washington R J 
Published: April 2011

Abstract
An investigation has been made of the interactions of the enzyme papain with the polycations protamine, polybrene, poly(L-lysine), spermine, spermidine and the neutral polymer polyvinylpyrrolidone (PVP). At low concentrations, each behaves as an inhibitor of the enzyme. As their concentrations increased above a certain level, the activity of the systems increased, and their inhibition of the enzyme appeared to be less pronounced. When acting by themselves in the presence of the substrate haemoglobin, each of the polycations was a weak proteolytic catalyst with a ranking of catalytic effectiveness of protamine &gt; polybrene &gt; poly(L-lysine) &gt; polyvinyl-pyrrolidone &gt; spermidine &gt; spermine. This effect could explain the anomalous inhibition of papain by these polycations. The interaction of papain with dansyl protamine (DNSP) and the extent of complex formation were studied using a fluorescence polarization technique and the results showed that there was a strong interaction occurred. The strength of binding was assessed by determination of the critical electrolyte concentration (0·2 M, NaNO3). The stoichiometry of the DNSP-papain complex was found to be 63 base moles of DNSP to one mole of papain.
Comparative Studies of the Effects of RS-8359 and Safrazine on Monoamine Oxidase In-vitro and In-vivo in Mouse Brain
Authors: Yokoyama Tomihisa , Karube Toshio , Iwata Nobuyoshi 
Published: April 2011

Abstract
The effect of RS-8359, (±)-4-(4-cyanophenyl)amino-6,7-dihydro-7-hydroxy-5H-cyclopenta[d]-pyrimidine on monoamine oxidase (MAO) has been compared with a hydrazinic MAO inhibitor, safrazine (β-piperonylisopropylhydrazine hydrochloride,) which is a MAO inhibitor used clinically. In-vitro radiochemical determination of MAO activity showed that the IC50 of RS-8359 was 0·52 μM for the deamination of 5-hydroxytryptamine (5-HT) in the mouse brain mitochondrial preparation, while β-phenylethylamine (PEA) deamination was inhibited by only 20% at 100 μM of the drug. 5-HT deamination in the brain homogenate prepared from mice killed 60 min after administration of RS-8359 was inhibited significantly by 14 and 48%, at 30 and 100 mg kg−1 (p.o.), respectively, while deamination of PEA was little affected at the same doses. On the other hand, safrazine strongly inhibited both 5-HT and PEA deaminations, but showed no selectivity toward the substrate used. The extent of MAO inhibition by RS-8359, measured fluorometrically with kynuramine as a substrate in the brain homogenate, was independent of preincubation up to 80 min. In contrast, the inhibitory potency of safrazine was strengthened by preincubation in a time-dependent manner. Oral administration of RS-8359 (3-30 mg kg−1) caused a dose-dependent increase in endogenous monoamines in mouse brain, which disappeared a few hours after its administration. Increase in monoamine content caused by safrazine lasted for at least 24 h. These results indicate that RS-8359 is a reversible and specific inhibitor of MAO-A, while safrazine is an irreversible and non-specific MAO inhibitor, in-vivo and in-vitro in mouse brain.
Effects of chronic nicotine pretreatment on (+)-amphetamine and nicotine-induced synthesis and release of [3H]dopamine from [3H]tyrosine in rat nucleus accumbens
Authors: Fung Yiu K 
Published: April 2011

Abstract
The effects of chronic (14 day) administration of nicotine (1·5 mg kg−1 day−1) on the rat nucleus accumbens have been examined. Pretreatment of animals with nicotine increased the endogenous level of dopamine. The ability of (+)-amphetamine to stimulate formation and release of [3H]dopamine from [3H]tyrosine was greatly potentiated in tissue slices from the nucleus accumbens of rats pretreated with nicotine. Furthermore, nicotine was effective in stimulating the formation and release of from [3H]dopamine from [3H]tyrosine in tissue slices from chronic nicotine-treated animals.
Influence of Plasma Protein Binding on the Brain Uptake of an Antifungal Agent, Terbinafine, in Rats
Authors: Machard Brigitte , Misslin Pierrette , Lemaire Michel 
Published: April 2011

Abstract
The intracarotid injection technique has been used to determine the unidirectional brain uptake of an antifungal, lipophilic agent, terbinafine (Lamisil, Sandoz Basle), in the rat. Ultrafiltration showed it to be highly bound to human plasma, human serum albumin (HSA), α-acid glycoprotein (AAG) and lipoproteins (VLDL, LDL, HDL). The effect of plasma protein binding of the drug on brain uptake was also examined with the technique. The lowest brain uptake was observed in the presence of plasma (6%); it varied from 23 to 30% with physiological concentrations of VLDL, LDL and HSA and was significantly higher (43–45%) in the presence of physiological concentrations of AAG and HDL. The free fraction as determined in-vitro and the brain uptake of the drug varied inversely with the plasma protein concentrations; however, the brain uptake was higher than expected from in-vitro measurements. These data indicate that the amount of circulating Lamisil available for brain penetration exceeds its free fraction; they also show that plasma proteins differently reduce the brain transport of the drug.
The Inhibitory Effects of Cannabinoids, The Active Constituents of Cannabis sativa L. on Human and Rabbit Platelet Aggregation
Authors: Formukong E A , Evans A T , Evans F J 
Published: April 2011

Abstract
Olivetol, cannabigerol (CBG), cannabidiol (CBD), cannabinol (CBN) and tetrahydrocannabinol (δ1-THC) were assessed for their ability to inhibit agonist-induced platelet aggregation and [14C]5-HT release. With the exception of olivetol, (40% maximal effectiveness), none of the compounds inhibited tetradecanoylphorbolacetate (TPA)-induced aggregation of human or rabbit platelets. All of these cannabinoids partially inhibited primary aggregation and totally inhibited secondary aggregation of human platelets when adrenaline was used as the agonist. Inhibition was dose-dependent over the range 10−3–10−5 M. Both rabbit and human platelet aggregation induced by adenosine diphosphate was inhibited in a dose-dependent manner and the order of potency was CBG &gt; CBD &gt; olivetol &gt; THC &gt; CBN, the IC50 of CBG being 2·7 × 10−4M. PAF-induced aggregation of rabbit platelets was also inhibited by these compounds in a dose-dependent manner over the concentration range 10−3 to 10−4 M, however [14C]5-HT release was only partially prevented by the cannabinoids in a manner which did not correlate with inhibition of aggregation.
Solubilization of Indomethacin by Polysorbate 80 in Mixed Water-Sorbitol Solvents
Authors: Attwood D , Ktistis G , Mccormick Y , Story M J 
Published: April 2011

Abstract
The effect of indomethacin on the micellar properties of the non-ionic surfactant, polysorbate 80, in water-sorbitol mixtures containing up to 25% w/v sorbitol has been investigated by light scattering, photon correlation spectroscopy and viscometric techniques. The molecular weight of polysorbate 80 micelles containing solubilized indomethacin increased linearly with increase of sorbitol concentration. Solubilization of indomethacin resulted in an increase of micellar weight due not only to the incorporation of solubilizate but also to an increase in the number of polysorbate molecules per micelle. The micelles in all systems were most satisfactorily represented as oblate ellipsoids, the asymmetry and hydration of which increased with increase of sorbitol concentration. Indomethacin solubilization caused a restructuring of the micelle to produce a more symmetrical micelle of increased hydration.
The Antiemetic Profile of Zacopride
Authors: Smith William L , Alphin Reevis S , Jackson Carlotta B , Sancilio Lawrence F 
Published: April 2011

Abstract
The antiemetic activity of zacopride against a variety of emetogenic agents has been determined in dogs. Zacopride was highly effective in inhibiting emesis due to a wide range of cancer chemotherapeutic agents, particularly cisplatin. It was well absorbed orally since the dose of zacopride required to inhibit cisplatin-induced emesis in dogs by 90% was 28 μg kg−1 both by i.v. and p.o. routes. Further, zacopride (1 mg kg−1 p.o.), administered after the onset of cisplatin-induced emesis, reduced the number of subsequent emetic episodes by 91%. Zacopride at 0·1, 1, or 3·16 mg kg−1 p.o. or i.v., reduced the number of emetic episodes due to dacarbazine, mechlorethamine, adriamycin, actinomycin D, or peptide YY by 100, 100, 86, 96 and 79%, respectively. However, zacopride was not effective in inhibiting emesis due to either apomorphine, copper sulphate, protoveratrine A, histamine, or pilocarpine. No adverse effects attributed to zacopride were observed. Zacopride is thus a unique and potent antiemetic agent as it selectively inhibits the emetic response to cancer chemotherapy agents and peptide YY.
Effects of 3,3′-di-O-methylquercetin on guinea-pig isolated smooth muscle
Authors: Abdalla Shtaywy , Zarga Musa Abu , Afifi Fatma , Al-Khalil Sulieman , Mahasneh Adel , Sabri Salim 
Published: April 2011

Abstract
The effects of the flavone 3,3′-di-O-methylquercetin (DOMQ) have been examined and compared with those of quercetin, on guinea-pig isolated ileum, trachea, and main pulmonary artery (MPA). Except for transient contractions induced by low concentrations (10−8-3 × 10−6 M), DOMQ and quercetin (up to 3 × 10−4M) caused reduction of the tone and the phasic contractions of the ileum. A23187 reversed the inhibitory effects of quercetin but not those of DOMQ. DOMQ and quercetin caused concentration-dependent relaxation of the trachea and the adrenaline-contracted MPA. DOMQ shifted to the right the concentration-effect curves induced by acetylcholine on the ileum and the trachea, and by adrenaline on MPA and those induced by CaCl2 on ileum, trachea and MPA. DOMQ also inhibited the contractions induced, in Ca2+-free EGTA-containing buffer, by histamine on ileum and by adrenaline on MPA. These observations suggest that DOMQ inhibits Ca2+ influx, Ca2+ release from intracellular stores and, more likely, Ca2+ binding to intracellular receptor proteins.
Pharmacokinetics of Quinacrine after Intrapleural Instillation in Rabbits and Man
Authors: Björkman Sven , Ove Elisson Lars , Gabrielsson Johan 
Published: April 2011

Abstract
Quinacrine was given by intrapleural instillation or intravenous infusion to 10 rabbits. The uptake of quinacrine from the pleural space was rapid and complete. The mean absorption half-life was approximately 7 min and the mean bioavailability was slightly in excess of 100%. Similar absorption characteristics generally applied in man, in a pilot study on four patients. In three of them, peak quinacrine plasma concentrations were reached that were far above the normal therapeutic range. Known systemic side-effects of quinacrine comprise CNS stimulation, toxic psychosis and convulsions. In view of the high bioavailability and the large doses used for pleural sclerosing (pleurodesis) in patients, neurological disease and psychiatric disturbances that predispose to CNS toxicity should be considered as contraindications to intrapleural quinacrine.