bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiarrhythmic effect of amperozide, a novel psychotropic compound with class III antiarrhythmic properties, on digoxin-induced arrhythmias in the guinea-pig
Authors: Höglund Peter , Eriksson Margareta , Christensson Erik G 
Published: April 2011

Abstract
Amperozide is a novel psychotropic compound with specific effect in limbic brain areas. Preliminary findings have also indicated an antiarrhythmic effect in-vitro. Injections of saline, amperozide, melperone, thioridazine, bretylium or lignocaine, were given i.p. to anaesthetized guinea-pigs, which 10 min later were given digoxin s.c. to induce arrhythmia. In a series of control experiments none of these compounds caused arrhythmia in combination with the vehicle of digoxin. The time to arrhythmia was significantly prolonged after treatment with amperozide, melperone and bretylium compared with saline, but there were no differences between the treatments. The digoxin concentrations in plasma at death varied considerably within the groups and no statistical significance was found.
Particulate contamination in plastic ampoules
Authors: Oppenheim Richard C , Gillies I Ross 
Published: April 2011

Abstract
Plastic ampoules of Water for Injections, JP, and Injection Sodium Chloride, JP, were investigated to determine their particle load. Four batches were studied. The ampoules were twist-opened as they would be in the clinical setting and the total particle load, both inherent and that created in opening, was determined by reading the contents with a HIAC 420 particle counter with a CMB 60 sensor. The total particle content was found to be minimal, easily complying with world L. V.P. standards and the S. V.P. standard of the USP XXI. The number of particles found in these opened plastic ampoules was significantly lower than that found in clinically snap-opened glass ampoules and also slightly lower than that found in laboratory heat-opened glass ampoules. Whilst the plastic ampoule has a restricted application because it is not suitable for all drugs, it is concluded that when they are used as the immediate container for Water for Injections and Injection Sodium Chloride they are highly effective in reducing the particulate contamination generated in opening.
Characterization of flufylline, fluprofylline, ritanserin, butanserin and R 56413 with respect to in-vivo α1-, α2- and 5-HT2-receptor antagonism and in-vitro affinity for α1-, α2- and 5-HT2-receptors: comparison with ketanserin
Authors: Korstanje C , Sprenkels R , Doods H N , Hugtenburg J G , Boddeke E , Batink H D , Thoolen M J M C , Van Zwieten P A 
Published: April 2011

Abstract
The experimental drugs butanserin (R 53393), ritanserin (R 55667), R 56413, flufylline (Sgd 195/78) and fluprofylline (Sgd 144/80) were evaluated with respect to their antagonism at postjunctional α1- and α2-adrenoceptors and 5-HT2-receptors in pithed rats. Moreoever, affinity for [3H]mianserin, [3H]prazosin and [3H]yohimbine binding sites was assessed using rat brain preparations. In all experiments ketanserin was taken as a reference compound. It is concluded that of the compounds investigated butanserin is the most potent and selective α1-adrenoceptor antagonist, whereas ritanserin was found to be a potent and selective 5-HT2-antagonist. Of the other compounds, fluprofylline was a very selective though not very potent α1-adrenoceptor antagonist. The other compounds were less active and less selective in this respect.
Buspirone decreases the activity of 5-hydroxytryptamine-containing dorsal raphe neurons in-vitro
Authors: Trulson Michael E , Arasteh Kamyar 
Published: April 2011

Abstract
Buspirone, a non-benzodiazepine anxiolytic agent, produced a dose-dependent decrease in the activity of 5-HT-containing dorsal raphe neurons recorded from mouse brain slices. The response was not changed in a low calcium/high magnesium incubation medium, indicating that the observed effects were the result of a direct action of buspirone on raphe neurons. These data are discussed within the context of the anxiolytic effects of buspirone.
Comparative lipophilicities of substrates of monoamine oxidase
Authors: Katayama Masako , Yamamoto Masato , Kobayashi Shinichi , Oguchi Katsuji , Yasuhara Hajime 
Published: April 2011

Abstract
Oil/water partition coefficients of various substrates of monoamine oxidase (MAO) and kinetic parameters of MAO-A and -B of rat liver at two pH values, pH 7 and pH 9, were investigated. Octanol, heptane or benzene were chosen for the oil phases. The deamination of the biogenic amines 5-hydroxytryptamine (5-HT), tyramine, 2-phenethylamine (PEA) and benzylamine was studied at pH 7 and pH 9. Results indicated all four substrates were very hydrophilic, and the oil/water partition coefficients of benzylamine and PEA were higher than those of 5-HT and tyramine. The changes in Km and Vmax values at pH 7 and pH 9 indicated that the affinities of MAO-A towards 5-HT and tyramine slightly increased at pH 9 and those of MAO-B towards tyramine and benzylamine also increased at pH 9, while uncharged amines at pH 9 amounted to about a hundred times of those at pH 7. It is concluded that the mitochondrial MAO bound to the membrane may metabolize charged molecules as well as uncharged counterparts.
α1-Adrenoceptor function in the rat hippocampus as assessed by noradrenaline-stimulated inositol phospholipid breakdown after destruction of noradrenergic neurons by neonatal 6-hydroxydopamine treatment
Authors: Fowler Christopher J , Fagervall Ingrid , Minor Bruce G , Ross Svante B 
Published: April 2011

Abstract
Neonatal 6-hydroxydopamine treatment of male Sprague-Dawley rats resulted in a large depletion of noradrenaline 84–87 days later, as demonstrated by an 82% reduction in the intra-synaptosomal deamination of [14C]noradrenaline within noradrenergic synaptosomes with only marginal effects upon the extrasynaptosomal deamination. The hippocampal stimulation of inositol phospholipid breakdown by noradrenaline was, however, unaffected by the neonatal 6-hydroxydopamine treatment.
In-vitro release of [14C]glutamate from dentate gyrus is modulated by GABA
Authors: Spencer P , Lynch M A , Bliss T V P 
Published: April 2011

Abstract
The effect of GABA (10−3 and 10−4 M) on the release of preloaded [14C]glutamate from slices of rat dentate gyrus, in response to K+ stimulation, was studied in Ca2+-free and normal Krebs solutions. Release in Ca2+-free solution was significantly enhanced, but there was no change in release in normal Krebs solution. These results imply that Ca2+-dependent (presumably neuronal) release of glutamate from the dentate gyrus is depressed by GABA, while non-neuronal Ca2+-independent release is enhanced.
Bulbocapnine is not a selective DA1 receptor antagonist
Authors: Kohli Jai D , Glock Dana , Goldberg Leon I 
Published: April 2011

Abstract
Antagonist activity of bulbocapnine on DA1 versus DA2 dopamine receptors was studied simultaneously in a dog under pentobarbitone anaesthesia and without phenoxy-benzamine pretreatment. Fenoldopam (SK&F 82526) injected into the renal artery was the DA1 agonist and dipropyl dopamine or piribedil injected into the femoral artery were the DA2 agonists. Both at 0.5 and 1 mg kg−1 doses intravenous bulbocapnine caused nearly equal inhibition of DA1 and DA2 dopamine receptor-mediated responses. Our results show that under these experimental conditions bulbocapnine is not a selective DA1 dopamine antagonist.
The role of adenosine in cerebral vascular regulation during reductions in perfusion pressure
Authors: Phillis John W , DeLong Robert E 
Published: April 2011

Abstract
The adenosine antagonist caffeine was used to test the hypothesis that endogenous adenosine contributes to the regulation of cerebral blood flow during acute reductions in mean arterial blood pressure. Caffeine, administered intraperitoneally in 20 and 40 mg kg−1 doses, failed to alter the autoregulatory flow responses to marked reductions in arterial blood pressure, showing that adenosine is not essential for cerebrovascular regulation during severe hypotension.
Inhibition of hepatic microsomal monooxygenase activity by cinchocaine: mechanistic studies and effects of ionization
Authors: Murray Michael 
Published: April 2011

Abstract
The quinoline-based local anaesthetic cinchocaine (dibucaine) was found to be a mixed-type inhibitor of microsomal aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase activities from control and phenobarbitone-induced rat liver in-vitro. Cinchocaine also elicited a characteristic type I optical difference spectrum in oxidized liver microsomes (Ks = 24 μm; ΔAmax = 3.4 × 10−3 absorbance units (nmol cytochrome P450)−1) but did not appear to bind to the reduced form of the cytochrome. Additional studies indicated that cinchocaine competitively inhibited the type I spectral binding of substrate (aminopyrine) to ferric cytochrome P450. Studies of monooxygenase inhibition by cinchocaine over a relatively narrow pH range (6.5–8.5) indicated that, as might be expected, the un-ionized form of the drug is associated with inhibitory potency superior to that of the ionized form. Thus 40% inhibition of aminopyrine N-demethylase activity was observed with 100 μm cinchocaine at pH 8.0 and 8.5 (24% and 50% un-ionized drug, respectively), whereas only 16% inhibition was observed at pH 6.5(1% un-ionized drug). These findings suggest that the inhibitory action of cinchocaine is mediated exclusively via an interaction with ferric cytochrome P450 and that the extent of ionization is a determinant of mixed function oxidase inhibition.
Effects of morphine and clonidine on sulphobromophthalein disposition in mice
Authors: Ben-Zvi Zvi , Hurwitz Aryeh 
Published: April 2011

Abstract
Levels of sulphobromophthalein (BSP) in plasma and liver were elevated by the opiate, morphine, and by the α2-adrenoceptor agonist, clonidine. Neither morphine, 1 mg kg−1, nor clonidine, 0.01 mg kg−1, affected BSP levels significantly. When given together at these doses, they caused BSP levels in plasma and liver to be raised. At 20 mg kg−1, the effect of morphine on BSP levels was maximal, as was that of clonidine, 1.0 mg kg−1. However, the effect of these drugs given together on plasma BSP exceeded the maximal effect of either alone. Yohimbine, an α2-adrenoceptor antagonist, did not affect BSP levels, nor did the opiate antagonist, naloxone. Each of these antagonists reversed the hepatobiliary effects of its respective agonist, as shown by return of BSP levels to those of saline-treated mice. Yohimbine did not reverse morphine, nor did naloxone reverse clonidine. The additive effects of morphine and clonidine and the specificities of their respective antagonists strongly suggest the involvement of discrete receptors mediating their essentially identical hepatobiliary effects.
Chromatographic separation of thioridazine sulphoxide and N-oxide diastereoisomers: identification as metabolites in the rat
Authors: Watkins Geraldine M , Whelpton Robin , Buckley Dennis G , Curry Stephen H 
Published: April 2011

Abstract
(±)-Thioridazine and (±)-desmethylthioridazine have been oxidized to produce a number of chiral sulphoxide and amine oxide compounds. Diastereoisomeric isomers were separated by thin-layer and high performance liquid chromatography. Thioridazine-5-sulphoxide, N-desmethylthioridazine-5-sulphoxide and thioridazine-N-oxide diastereoisomers were found to be thioridazine metabolites following dosing in rats or after in-vitro incubation with rat liver homogenate.
Brittle fracture propensity measurements on ‘tablet-sized’ cylindrical compacts
Authors: Roberts R J , Rowe R C 
Published: April 2011

Abstract
The brittle fracture propensity test which was originally designed for large, square compacts with a central hole has been modified and extended to compacts of ‘tablet-sized’ dimensions. This allows a brittle fracture propensity (BFP) index to be measured at strain rates and conditions approaching those normally used in tableting. The BFP indices for microcrystalline cellulose, Tablettose and heavy magnesium carbonate were evaluated at punch velocities of 3.33 and 200 mm s−1 and found to be in good agreement with the results of previous workers.
The disposition of pyrimethamine in the rat isolated perfused liver: the effect of suramin
Authors: Coleman M D , Adjepon-Yamoah K 
Published: April 2011

Abstract
The pharmacokinetics of pyrimethamine (0.5 mg) were determined in the rat isolated perfused liver in the presence of suramin (17.75 mg). The clearance, half life, area under the curve, and volume of distribution of pyrimethamine were unaffected by the concurrent administration of suramin, as was the hepatic sub-cellular disposition of the drug. This report is of relevance to the future concurrent administration of suramin and pyrimethamine in West Africa.
Hypherphagia caused by muscimol injection in the nucleus raphe dorsalis of rats: its control by 5-hydroxytryptamine in the nucleus accumbens
Authors: Bendotti C , Garattini S , Samanin R 
Published: April 2011

Abstract
Muscimol injection in the nucleus raphe dorsalis caused intense eating by rats with access to food. A dose-related reduction of muscimol's effect was found after bilateral injections of 5-hydroxytryptamine (5-HT) in the nucleus accumbens (dose range 2.2–8.8 μg in 2 μl) but no effect was observed when an even higher dose (17.6 μg) of 5-HT was injected in the caudate putamen. Eating by food-deprived rats was not changed by any dose of 5-HT injected either into the nucleus accumbens or the caudate putamen. (+)-Norfenfluramine, 20 μg, injected in the nucleus accumbens also reduced muscimol-induced eating but had no effect on the food intake of starved rats. The results suggest an important role of 5-HT in the nucleus accumbens in the control of certain types of hyperphagia in rats.
Haem arginate: a new stable haem compound
Authors: Tenhunen R , Tokola O , Lindén I-B 
Published: April 2011

Abstract
Intravenous administration of haem in acute hepatic porphyrias inhibits the induction of β-aminolaevulinic acid synthase, reduces the formation of potentially harmful metabolites of porphyrin synthesis and corrects the haem deficiency. Typically, haem therapy has been given in the form of haematin—haem dissolved in alkali. Such haematin solutions are, however, extremely unstable. Thus, the rapid decomposition of this therapeutic agent may have been responsible for the ineffectiveness of treatment in some clinical states and adverse reactions may have been caused by haematin degradation products. There is, therefore, a need for a stable, effective and well-tolerated haem preparation. We have prepared certain highly soluble haem compounds of which haem arginate has proved to be the most promising. Pure haemin was isolated from HIV and hepatitis B negative human blood. The haem derivatives prepared were screened as substrates for haem oxygenase. Haem arginate and haem lysinate were found to be as good substrates as methaemalbumin. Stock solutions of haem arginate were stable for 2 years at +6 °C. After dilution with sterile isotonic saline the haem arginate infusion was clearly more stable than haematin solutions made in the laboratory or prepared by dissolving commercial lyophilized haematin. The antiporphyrogenic effect of haem arginate (even after storage for two years) in 2-allyl-2-isopropylacet-amide-induced experimental porphyria of rats was equal to that of freshly prepared haematin. The acute oral toxicity of haem arginate was low compared with the parenterally administered drug, indicating poor oral bioavailability. The acute toxic effects after high intravenous or intraperitoneal doses were directed to the liver. Conventional haematin caused thrombophlebitic reactions at the site of infusion in all rabbits, but haem arginate did not cause any thrombophlebitis even after repeated infusions. The dose of haem arginate used in clinical trials, 0&#x006d;̇2 mg of haem kg−1 min−1 during 15 min (= total dose 3 mg kg−1 diluted in 100 mL isotonic saline), did not cause any clinically significant changes in the numerous haemostatic parameters measured in patients, and ten times higher infusion rates or total doses were needed to cause a decrease in the blood pressure of rats. Haem arginate has proven to have many advantages over conventional haematin solutions.
The effect of prostaglandins on gastric parietal and non-parietal secretion in the anaesthetized rat
Authors: Bunce K T 
Published: April 2011

Abstract
The effects of prostaglandin E2 (PGE2), 16,16-dimethyl prostaglandin E2 (dmPGE2) and prostaglandin F2α (PGF2α) on gastric secretion have been examined in the anaesthetized rat. The prostaglandins stimulated the secretion of a non-parietal juice which was rich in Na+ and Cl- with smaller amounts of K+ and HCO3-. Doses of the prostaglandins that stimulated gastric non-parietal secretion also inhibited histamine stimulated gastric acid secretion, and thus the same rank order of potency was obtained for the prostaglandins on the two secretory mechanisms, viz. dmPGE2 &gt; PGE2 &gt; PGF2α. During the secretion of endogenous gastric acid the secretagogue effect of the prostaglandins on non-parietal secretion was diminished, and this effect appeared to be due to the presence of intraluminal acid since it was mimicked by application of exogenous HCl to the gastric mucosal surface. Thus, the present results show that prostaglandins affect both the parietal and non-parietal secretions in the rat stomach and that these mechanisms show some interdependence.
Biodegradable microspheres: polyacryl starch microparticles as a delivery system for the antileishmanial drug, sodium stibogluconate
Authors: Baillie A J , Coombs G H , Dolan T F , Hunter C A , Laakso T , Sjöholm I , Stjärnkvist P 
Published: April 2011

Abstract
Liver parasite burdens of Leishmania donovani in the mouse have been determined after treatment with intravenous administration of sodium stibogluconate in the free or carrier form. The carrier form, in which the drug was covalently bound to polyacryl starch microparticles, was up to 100 x more effective than the free form in this murine model of visceral leishmaniasis. Empty microparticles had no effect on liver parasite burdens and the enhanced in-vivo antileishmanial activity of the carrier form of the drug was apparently due to passive drug delivery to the infected liver.
Metabolic N-oxidation of metronidazole
Authors: Essien E E , Ogonor J I , Coker H A B , Bamisile M M 
Published: April 2011

Abstract
Metronidazole when treated at the N-3 nitrogen with a mixture of hydrogen peroxide and acetic acid, or liver homogenate preparations, yields the N-3 oxide as identified by thin-layer chromatographic analysis on silica gel G, RF 0&#x006d;̇62 in ethanol-chloroform-ammonia (50:49:1), by chemical reduction with sulphur dioxide, and by ultra-violet spectrophotometry and nuclear magnetic resonance spectroscopy. Incubation of metronidazole at 37°C with rat liver 10 000g supernatant fortified with cofactors gave a product with identical chromatographic and UV spectral data suggesting that metronidazole like other tertiary amine drugs undergoes microsomal N-oxidation.
Rhein: an anthraquinone that modulates superoxide anion production from human neutrophils
Authors: Mian M , Brunelleschi S , Tarli S , Rubino A , Benetti D , Fantozzi R , Zilletti L 
Published: April 2011

Abstract
Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid), the active metabolite of diacetylrhein, which has been reported as an effective antirheumatic drug in man, inhibited superoxide anion production from human neutrophils challenged with N-formylmethionyl-leucyl-phenylalanine (FMLP: IC50, 2 times 10−5 M) and A23186 (IC50, 10−5M), but not with phorbol myristate acetate. In the same concentration range (10−6-10−3M), the drug did not affect oxy-radical production by a cell-free hypoxanthine-xanthine oxidase system and exerted weak inhibitory effects on FMLP-evoked lysosomal enzyme release. Rhein inhibitory effects on neutrophil functioning may contribute to the overall therapeutic activity of the parent drug, diacetylrhein.
Distribution and urinary excretion of the desethylmetabolites of chloroquine in the rat
Authors: Salako L A , Ajayi Funmilayo O 
Published: April 2011

Abstract
The tissue distribution of desethylchloroquine and bis-desethylchloroquine has been studied in rats after single intraperitoneal administration of the drugs at a dose of 10 mg kg−1. Concentrations of the chloroquine metabolites in the liver, heart, lungs, kidney and spleen were 34 to 250 times higher than their plasma concentrations 24 h after the drugs had been injected. Urinary excretion of the drugs was studied in rats after single intravenous administration of 2&#x006d;̇5, 5 or 10 mg kg−1 doses. The total estimated urinary excretion of desethylchloroquine and bisdesethylchloroquine was 25 and 64% respectively of the administered dose, with the maximum urinary excretion occurring on the first day. The results show that the desethylmetabolites of chloroquine are concentrated in the tissues in the same manner as the parent compound.
The angle of internal flow as an indicator of filling and drug release properties of capsule formulations
Authors: Newton J M , Bader F 
Published: April 2011

Abstract
The cohesiveness of size fractions of acetylsalicylic acid and lactose alone and in various combinations has been determined by estimation of the rate of decrease in volume as a function of tamping under standard conditions. The cohesiveness was quantified in terms of empirically derived characteristic, the angle of internal flow ϕ. The value of ϕ was found to decrease with the particle size of acetylsalicylic acid, but not lactose, and was found to be dependent on the relative proportion and particle sizes of acetylsalicylic acid and lactose when blends of powder were studied. The value of the time for 50% of the drug content to be released from a hard gelatin capsule in an in-vitro dissolution test, T50, was found to decrease with decreasing values of ϕ for capsules containing acetylsalicylic acid alone. For capsules containing powder blends there was no consistent relationship between the value of T50 and ϕ.
An investigation of the mechanism involved in the cholinergic action of meptazinol
Authors: Hetherington M S , Hughes I E , Lees A 
Published: April 2011

Abstract
In concentrations above 20 μM, (±)-meptazinol produced a contraction of the guinea-pig isolated ileum and this effect was antagonized by atropine (0.01 to 0.3 μM) in a manner which was not competitive. Cooling the preparation to 15 °C blocked the contractile action of meptazinol and of dimethylphenylpiperazinium (DMPP) but did not affect the action of carbachol. Twitch responses of the rat phrenic nerve-diaphragm preparation induced by indirect electrical stimulation in the presence of naloxone (20 nM) were potentiated by meptazinol (1 to 40 μM) which also reversed a partial blockade of the twitch induced by tubocurarine. Neither of these effects was seen in tissues which had been pretreated with the cholinesterase inhibitor BW284C51 (0.2 μM) though tetraethylammonium iodide (40 μM) was still able to enhance the responses to stimulation. In the presence of naloxone (20 nM) electrically induced responses of the rat isolated rectum were abolished by cinchocaine (10 μM), partially blocked by atropine (0.1 to 0.4 μM) and potentiated by meptazinol (1 to 30 μM). The latter action was not seen when meptazinol was administered in the presence of BW284C51. It is concluded that the cholinergic action of meptazinol in these tissues is due to an indirect effect, probably involving inhibition of cholinesterase and that no evidence was seen of any ability to increase the release of acetylcholine itself.