bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardioregulatory properties of indoramin in the rat
Authors: ALGATE D R , RASHID S , WATERFALL J F 
Published: April 2011

Abstract
The antihypertensive action of the competitive α-adrenoceptor antagonist indoramin is not accompanied by reflex tachycardia in animals or man. The possibility that the established local anaesthetic property of indoramin is involved in its cardioinhibitory action has been investigated. Indoramin evoked a dose-dependent bradycardia in anaesthetized/pithed rats. The decrease in heart rate was slightly greater than that evoked in anaesthetized intact animals suggesting that indoramin had a direct action on the heart. Reflex tachycardia was simulated in pithed rats by increasing the frequency of cardiac nerve stimulation from 0·3 to 1 Hz. Indoramin and the local anaesthetic agents, lignocaine and procaine, reduced the positive chronotropic response without markedly altering the basal rate. The response curves were parallel. In contrast, phentolamine decreased the positive chronotropic response, but only at high doses which were associated with a marked decrease in the basal rate. Thymoxamine and prazosin had no significant effects on the chronotropic response. These experiments suggest that the cardioregulatory action of indoramin is attributable to its local anaesthetic property and this action further distinguishes it from the other α-adrenoceptor antagonists tested.
Free fraction change with differing volume ratios in equilibrium dialysis: cases of non-linear drug-protein binding
Authors: BEHM HARRIET L , WAGNER JOHN G 
Published: April 2011

Abstract
When equilibrium dialysis is used to measure drug-protein binding, an increase in the volume ratio (buffer solution/protein solution) causes a decrease in the total drug concentration at equilibrium. When binding is non-linear, this decrease in total drug concentration also causes a decrease in the free fraction. By use of the same volume ratio (3:1) binding curves were obtained for the binding of prednisolone to plasma proteins, and for the binding of salicylic acid and tolmetin to human serum albumin (HSA). When the volume ratio was changed, the observed free fractions were appreciably different from those expected by taking into account only the changes in the total equilibrium drug concentration. There is evidence that this phenomenon is the result of competition for binding sites between the drug and an impurity in the HSA. The effects are not the result of the presence of free fatty acids.
The effect of stress and indomethacin, carbenoxolone, salbutamol, metiamide, zolimidine and CF19415 on rat gastric mucus
Authors: GREEN A P , LANDER J E , TURNER D H 
Published: April 2011

Abstract
A method for measuring mucus adherent to the gastric mucosa using the dye alcian blue has been evaluated. Mucus was reduced by cold-restraint stress, reserpine and pyloric ligation, but not by 18 h fasting or indomethacin. The fasting mucus level was increased by carbenoxalone, but not by salbutamol or metiamide, and zolimidine only prevented the reduction in mucus induced by stress. A novel compound, 2-α-methoxyiminopyrazine acetonitrile (CF 19415), at 100 mg kg−1 orally increased alcian blue binding in fasted rats and in a cold restraint test, 100 mg kg−1 orally inhibited gastric damage and stimulated mucus secretion.
Inhibitory effect of two steroids on the accumulation of [3H]metaraminol by rat tissues in vivo
Authors: DAVILA D , IVANOV ROZA , DAVILA TATJANA 
Published: April 2011

Abstract
The present experiments were designed to investigate the effect of methylprednisolone and dexamethasone on tritiated metaraminol uptake in the whole animal. Rats received i.p. injections of methylprednisolone (5, 10 and 20 mg kg−1) or dexamethasone (1, 2 and 4 mg kg−1) on each of 3 consecutive days. Under light ether anaesthesia 5 min before death the rats received radioactive metaraminol (3 μg kg−1) via the femoral vein. Samples of various organs were removed and prepared for scintillation counting. The highest radioactivity was observed in the lungs and heart, followed by the kidney medulla, aorta, kidney cortex and submaxillary gland. Both steroids significantly inhibited uptake of metaraminol in the tissues examined. Dexamethasone seems to be more potent than methylprednisolone. It is concluded that these steroids may modify the uptake mechanism responsible for inactivation of the sympathomimetic neurotransmitter.
A polymeric film responding in diffusion properties to environmental pH stimuli: a model for a self-regulating drug delivery system
Authors: ALHAIQUE F , MARCHETTI M , RICCIERI F M , SANTUCCI E 
Published: April 2011

Abstract
A new polymeric film, ethylene-vinyl-NN-diethylglycinate random copolymer, has been studied to evaluate possible applications of such a material to produce controlled release dosage forms. Protonation of the substituted amino groups took place to different extents according to environmental pH conditions. The polymeric film proved to be permeable only to uncharged species, the rate of diffusion of which increased with the increasing charge of the membrane. This effect might be related to strong polymer-proton interactions affecting structure and transport properties of the film and enhancing the solvation process. The charged form of a number of barbituric acid derivatives did not diffuse through the membrane. The uncharged forms permeated the polymeric sheeting at rates consistent with their partition coefficients and which increased with the increasing charge of the polymer.
Kainic acid lesions of striatum and decortication reduce specific [3H]sulpiride binding in rats, so D-2 receptors exist post-synaptically on corticostriate afferents and striatal neurons
Authors: THEODOROU A , REAVILL C , JENNER P , MARSDEN C D 
Published: April 2011

Abstract
Unilateral kainic acid lesions of rat striatum reduced specific striatal [3H]spiperone and [3H]sulpiride binding sites (Bmax) by 52 and 67% respectively compared with the intact side. The dissociation constant (KD) for [3H]spiperone binding was unchanged but that for [3H]]sulpiride binding was reduced. Specific striatal [3H]spiperone and [3H]sulpiride binding was reduced by 22 and 37% respectively in unilateral decorticate animals, but there was no change in KD. Unilateral 6-hydroxydopamine lesions of the medial forebrain bundle caused no change in striatal [3H]spiperone binding sites or KD value, but produced a 27% increase in [3H]sulpiride binding sites with no change in KD. These data support the hypothesis of D-2 receptors located on cortico-striate glutamate fibres, but also indicate the presence of both D-1 and D-2 receptors on the cell bodies of striatal neurons.
Whole brain tyrosine hydroxylase activity during the development of deoxycorticosterone acetate-1% sodium chloride-induced hypertension in rats
Authors: JACKSON NIGEL , GULLIVER PETER A , DEAN HARVEY G 
Published: April 2011

Abstract
Water was chosen as the optimal medium for the extraction of tyrosine hydroxylase (TH) from rat brain. Determination of TH activity in crude homogenates failed to exhibit a linear relationship between enzyme concentration and measured activity, however, when a supernatant was used, a linear relationship existed. At a time when TH activity is maximally increased in the locus coeruleus after reserpine treatment (Reis et al 1975; Zigmond 1979) (2.5 mg kg−1 day−1 for 3 days, kill 24 h after last dose) we could detect no alterations in whole brain TH, however if treatment continued for 4 days and animals were killed 72 h after the last dose it was possible to detect increases in TH activity in various brain regions. These results suggest that local changes in brain TH activity are not revealed in measurements made on whole brain. The early rise in blood pressure, following the administration of deoxycorticosterone acetate (doca) and 1% NaCl to male Wistar rats, was accompanied by bradycardia. Whole brain TH activity was determined in these hypertensive animals 6–21 days after the commencement of treatment and the results failed to confirm the reported elevation of TH activity (Rylett et al 1976). The results are discussed with reference to the TH assay employed.
The neuromuscular and autonomic blocking effects of azasteroids containing choline or acetylcholine fragments
Authors: MARSHALL I G , HARVEY A L , SINGH H , BHARDWAJ T R , PAUL D 
Published: April 2011

Abstract
Nine analogues of the azasteroid muscle relaxant chandonium have been tested for neuromuscular blocking activity, ganglion blocking activity, inhibitory effects on cardiac muscarinic receptors, and for effects on noradrenergic transmission. Experiments were performed in anaesthetized cats and in isolated preparations. The two bisquaternary compounds HS-626 and HS-627, choline and acetylcholine-like analogues of chandonium respectively, were approximately equipotent with chandonium as neuromuscular blocking agents in the cat, but HS-672 possessed slightly more vagal blocking action. No evidence was obtained for ganglion block. The monoquaternary analogues, HS-408 and HS-465 and two 4-aza-androstanes, (HS-522 and HS-523) were more than 100 times less active than the bisquaternary compounds as neuromuscular blocking agents, and produced vagal blockade and ganglion blockade at sub-neuromuscular blocking doses. pA2 determinations in the chick biventer cervicis muscle, the guinea-pig atria and guinea-pig ileum showed that the bisquaternary compounds chandonium, HS-626 and HS-627 were much more potent in blocking cardiac than intestinal muscarinic receptors and that HS-626 possessed the widest margin between concentrations blocking the nicotinic receptors at the neuromuscular junction and the cardiac muscarinic receptors. Evidence for the three bisquaternary compounds blocking neuronal noradrenaline reuptake was obtained only at very high concentrations. HS-626 possessed a slightly more desirable spectrum of activities than chandonium, but the degree of improvement over the parent compound is insufficient to merit extensive clinical testing.
Determination of interparticulate forces in ordered powder mixes
Authors: STANIFORTH J N , REES J E , LAI F K , HERSEY J A 
Published: April 2011

Abstract
The theory of interparticle bond formation is considered with particular reference to ordered powder mixing. A technique is described for measuring the interparticle adhesion forces between drug and excipient particles bound in ordered units. The method uses a specially constructed ultracentrifuge rotor tube insert such that fine adherent particles can be separated from coarser carrier particles in ordered mixes. The ordered units are held behind a screen in the rotor tube insert and when the forces generated by ultracentrifugation become greater than the interparticle adhesion forces the ordered units break down into their component particles. Adhesion profiles were obtained for four different ordered mixes containing drug and excipient powders by plotting force of adhesion against the cumulative percentage of fine drug particles adhering to the carrier particle surface. The adhesion profile is influenced by the quantity of drug powder adhering to the excipient carrier particle surface. Above a critical drug content, each ordered mix shows a ‘composite' adhesion profile consisting of two distinct curves linked by a lag period. The initial curve, preceding the lag period, appears to correspond to loss of large amounts of weakly bound drug particles; after the lag period only relatively strongly adhered particles are removed and this phase occurs more gradually. The critical drug concentration is related to the surface properties of the excipient and drug particles which determine the strength of adhesion forces within an ordered unit.
Influence of coating and core modifications on the in vitro release of methylene blue from ethylcellulose microcapsules produced by pan coating procedure
Authors: BROPHY M REGINA , DEASY P B 
Published: April 2011

Abstract
Core pellets containing methylene blue, a highly water-soluble drug, lactose and polyvinylpyrrolidone (PVP) were produced and coated by pan technology with ethylcellulose 7 cp. Scanning electron microscopy revealed that larger microcapsules were aggregates of smaller microcapsules which remained intact during the dissolution testing. The coating appeared porous with rough and smooth areas. Polymer disc studies confirmed a lack of swelling of the ethylcellulose used when in contact with the dissolution medium. Modifications of the coating applied included addition of hydroxypropylmethylcellulose (a cofilm former), diethyl phthalate, di-n-butylphthalate and castor oil (plasticizers), talc (an extender and anti-tack agent) and paraffin wax and hydrogenated castor oil (waxy sealants) to the coating solution. Most products had released 50% drug after about 20 min dissolution treatment although the inclusion of the waxy sealants in the coating markedly retarded release during the first 60 min. In contrast, the inclusion of hydrogenated castor oil or polyethylene powder in the core, retarded dissolution of the drug over 3 h but tended to produce a coarser product. Other modifications of the core were addition of hydroxypropylmethylcellulose, carnauba wax-beeswax (1:1) and carnauba wax, with little retardation of drug release. The mechanism of drug release from the microcapsules was complex involving mainly diffusion.
Acetylcholine release from the myenteric plexus of guinea-pig ileum by prostaglandin E1
Authors: YAGASAKI O , TAKAI M , YANAGIYA I 
Published: April 2011

Abstract
Release of acetylcholine (ACh) by prostaglandin E1 from the nerve terminals of the guinea-pig longitudinal muscle strip was studied in order to reveal the effect of PGE1 on myenteric plexus activity. The ACh released was collected in the presence of physostigmine (2·1 μg ml−1) and choline (0·1 μg ml−1) at 38° C. Five to 100 ng ml−1 PGE1 enhanced the release dose-dependently. The effect was maintained during the presence of PGE1 in the organ bath, while rapid tachyphylaxis was observed with the ACh-releasing action of nicotine. Tetrodotoxin or morphine almost completely inhibited the effect of PGE1 on ACh release. Hexamethonium, in a concentration which completely blocked the effect of nicotine, partially inhibited the effect of PGE1. In the late phase of nicotine action, the tissue was still sensitive to PGE1 despite the continued exposure to nicotine. These data suggest the presence in the myenteric plexus of PG receptors which can increase ACh release.
Influence of 1,8-dihydroxyanthraquinone and loperamide on the paracellular permeability across colonic mucosa
Authors: VERHAEREN E H C , DREESSEN M J , LEMLI J A 
Published: April 2011

Abstract
Administration of 1,8-dihydroxyanthraquinone (DHA) markedly increases the permeability of guinea-pig colonic mucosa. In 1 h 25% of the administered dose of99m Tc-EDTA complex leaks through the mucosa. Orally administered loperamide blocks the99m Tc-EDTA transfer after DHA administration. Loperamide injected in situ in the ligated colon segment shows the same blocking properties of the transfer rate of the complex. These findings suggest that the opposing action on fluid transport of the laxative DHA and the antidiarrhoeal loperamide could be due to these drugs affecting the permeability of the colonic mucosa. The minimal dose of loperamide, able to restore normal permeability, was as low as 0·01 mg kg−1.
Influence of deaminated metabolites on the relaxing effect of dopamine on dog saphenous vein
Authors: TEIXEIRA F , MACEDO T R A 
Published: April 2011

Abstract
The relaxing effect of dopamine was studied on the dog isolated saphenous vein contracted by prostaglandin F2α after α-adrenoceptor blockade by phentolamine. This effect is partially inhibited by propranolol and haloperidol suggesting that dopamine has two types of receptors in this vessel: β- and dopaminergic receptors. However, the results obtained after treatment with drugs that interfere with deamination of catecholamines or after denervating the venous tissue led us to conclude that the agonist substance is not dopamine, but probably one of its deaminated metabolites or a secondary condensation product, namely tetrahydropapaveroline. Adrenaline has also been used to compare the behaviour of the two amines when interference in the deamination process is produced. The dissimilar results obtained with adrenaline are in good agreement with the hypothesis.
Theoretical considerations of the influence of polymer film coatings on the mechanical strength of tablets
Authors: STANLEY P , ROWE R C , NEWTON J M 
Published: April 2011

Abstract
A theoretical analysis of the influence of polymer film coatings on the mechanical strength of tablets has been undertaken. Making some basic assumptions, the theory predicts that neither the thickness of the substrate nor that of the coating has any influence on which fractures first, this being solely determined by the ratio of the tensile fracture strength to the Young's modulus for the two materials. Such a finding suggests that in practice for film-coated tablets the substrate will usually fracture before the coating. Simple measurements of maximum failure loads are of little value in assessing the influence of film coating on the mechanical strength of tablets.
Comparison of the in vitro dissolution behaviour of various indomethacin formulations with their in vivo bioavailability
Authors: ROWE J S , CARLESS J E 
Published: April 2011

Abstract
The effects of the core to colloid wall ratio and particle size of the core on the in vitro release of indomethacin microcapsules prepared by the gelatin-acacia complex coacervation process have been examined. All formulations showed a zero order release pattern after an initial burst phase. The release rate increased with increasing core to coat ratios and decreasing particle size of core material. In vivo plasma level studies showed no difference in bioavailability between different microcapsule formulations or a conventional indomethacin capsule. In vitro release studies on a commercially available sustained release formulation of indomethacin (Indocid R) were slower than any of the microcapsule formulations and exhibited a √t dependence indicating a diffusion controlled process from a matrix formulation. In vivo studies show this formulation to have a longer, smoother plasma concentration than the microcapsule formulation, and to avoid high initial peak values of drug. Thus from the in vitro studies a sustained release effect was not unexpected but the in vitro differences between the microcapsule products were not paralleled by the in vivo behaviour. These results illustrate some of the problems in extrapolation of in vitro dissolution data to the in vivo situation.
Enhancement of the intestinal absorption of ergot peptide alkaloids in the rat by micellar solutions of polyoxyethylene-24-cholesteryl ether
Authors: FRANZ J M , VONDERSCHER J P 
Published: April 2011

Abstract
The incomplete intestinal absorption of hydrogenated ergot peptide alkaloids as measured in bile duct cannulated rats is much increased when the ergot compounds are administered as micellar solutions together with POE-24-cholesteryl ether. In vitro diffusion experiments with isolated intestinal mucus show that the ergot peptide alkaloids are strongly retained by the mucus layer. It is suggested that the diffusion of the ergot compounds across the mucus barrier is facilitated by micellar entrapment of the drug.
Histamine receptors in the guinea-pig duodenum
Authors: BERTACCINI G , ZAPPIA L 
Published: April 2011

Abstract
Guinea-pig duodenum contracted by histamine or by acetylcholine was relaxed dose-dependently by a series of H2-receptor selective agonists namely dimaprit, impromidine, clonidine and tolazoline. This relaxation was not neurally mediated since it was not modified by tetrodotoxin nor was it exerted through sympathetic receptors because it was not modified by pretreatment with propranolol or phentolamine. Apparently it was connected with the H2-receptor stimulation more than to peculiarities of the single compounds. However a series of H2-blockers (metiamide, cimetidine, ranitidine or oxmetidine) were unable to counteract the effect of the H2-agonists or the relaxant effect of histamine in the presence of chlorpheniramine. This peculiar situation seems to indicate the existence of anomalous H2-receptors, susceptible to the action of the agonists but not to that of the antagonists.
Effect of slugging pressure on the properties of granules and tablets prepared from potassium phenethicillin
Authors: KHAN K A , MUSIKABHUMMA P 
Published: April 2011

Abstract
The mechanism of preparing compacts by precompression has been investigated. The influence of slugging pressure on the bulk and tapped density, particle size distribution and the surface area of precompressed granules has been examined. The slugged granules have been tableted and the effect of compaction force on the weight uniformity, friability, crushing strength, disintegration time, dissolution rate and internal surface area of the tablets has been studied. The results show that the granules obtained from 15·9 mm slugs manufactured at low compaction forces (e.g. 49 MNm−2) had a lower bulk density, higher friability and larger surface area than those made at higher compaction pressures (e.g. 196 MNm−2). The lighter granules compacted into stronger tablets over a range of compaction forces and the effect was attributed to greater intergranular bonding caused by increased plastic flow.
The effect of DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine) on monoamine oxidase activities in tissues of the rat
Authors: LYLES GEOFFREY A , CALLINGHAM BRIAN A 
Published: April 2011

Abstract
The in vitro inhibition of monoamine oxidase (MAO) in rat liver, and of the clorgyline-resistant amine oxidase (CRAO) in rat heart and aorta, by DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine) has been studied. Inhibition of each enzyme activity was independent of prolonged preincubation, was reversed by dialysis, and also Ackermann-Potter plots were consistent with reversible inhibition. Simple linear competitive inhibition of MAO-A and MAO-B was observed, with Ki values of 6 × 10−6 and 8 × 10−5 m, respectively. CRAO was inhibited in a mixed, non-competitive manner (Ki of 3·2 × 10−5 and 7·8 × 10−6 m in heart and aorta, respectively) which conformed to a kinetic model in which the binding of DSP-4 to CRAO increased the affinity of substrate binding, but prevented product formation. The possible significance of these results for the in vivo actions of the drug is discussed.
Some biochemical aspects of the potential benefit of associating MD780515 with tricyclic antidepressants
Authors: DOSTERT P , BENEDETTI M STROLIN , SONTAG N 
Published: April 2011

Abstract
In the rat, suitable oral doses of tricyclic antidepressants (amitriptyline 20 mg kg−1, imipramine, desipramine 2·5 mg kg−1) are able to antagonize the increase of cardiac levels of intravenous tyramine after a pharmacologically active dose (3·5 mg kg−1 orally) of a reversible and specific type A MAO inhibitor, MD780515 (3-[4-(3-cyanophenyl-methoxy)phenyl]-5-(methoxymethyl)-2-oxazolidinone). MD780515, in oral doses up to 35 mg kg−1, does not alter the liver microsomal drug metabolizing enzymes in the rat. Therefore, when given with tricyclic antidepressants, it should not interfere with their metabolism.