bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioassay of vasopressin on the rabbit isolated urinary bladder
Authors: Angelucci L , Erspamer G Falconieri , Negri L
Published: April 2011

The rabbit isolated urinary bladder contracted in the presence of Lys8-vasopressin from threshold concentrations of 5 to 30 μ ml−1 (0·02 to 0·11 ng ml−1). Responses were proportional to the dose used. The tissue gave satisfactory results either fresh or after storage for several days in cold Tyrode or Krebs solution (3–4°). The preparation also contracted in the presence of oxytocin, but it was 7 to 20 times less sensitive to this peptide. A number of other peptides and amines known to stimulate smooth muscle showed low activity on the rabbit urinary bladder and, occasionally, intense tachyphylaxis.
An assay for phenylephrine applicable to stability studies
Authors: Shotton E , Priaulx D J
Published: April 2011

An assay specific for phenylephrine, in the presence of decomposition products, is described. The procedure depends on the separation of the active constituent by cationic exchange resin and the subsequent determination of the ultraviolet absorbance at two selected wavelengths. The method was evaluated using a grossly decomposed buffered solution of phenylephrine hydrochloride, and it was found that phenylephrine could be assayed selectively under these severe conditions. Several other reported methods were also evaluated under these conditions.
Relation between structure of sulphonamides and inhibition of H2-pteroate synthesis in Escherichia coli
Authors: Thijssen H H W
Published: April 2011

Inhibitory activities for cell-free H2-pteroate synthesis in E. coli have been estimated for a heterogeneous series of N1-substituted sulphonamides and for N1N1-dialkyl-sulphonamides. The relation between the cell-free activities and the acid dissociation constants of the N1-substituted sulphonamides showed a parabolic dependency, indicating that the common parabolic relation between antibacterial activity and acidity of sulphonamides is not, as stated by the Breuckner and Cowles theory, a penetration phenomenon. The extent of ionization of the sulphonamides significantly affects the amount of inhibition of H2-pteroate synthesis. Evidence has been obtained that not only the ionized sulphonamide molecules interfere with the enzyme system, but the unionized molecules also contribute to affinity for the enzyme. The non-acidic N1N1-dialkyl-sulphonamides inhibited cell-free H2-pteroate synthesis. Some of the N1N1-dialkyl-sulphonamides showed higher affinity for the enzyme than their mono-substituted parent compounds. The relations between sulphonamide structure and cell-free activity are explainable by the Bell and Roblin theory.
Effect of l-dopa in 54Mn incorporation by tissues
Authors: Bonilla Ernesto , Diez-Ewald Maria , Medrano José Finol
Published: April 2011

54Mn incorporation by tissues was studied in 24 rats fed with excess manganese diet and in 31 fed a normal diet. The effect of intraperitoneally administered l-dopa (100 mg kg−1) on randomly selected rats in each group was determined. Manganese uptake in liver was higher in normally fed rats that received l-dopa; however, the manganese loaded rats showed a lower level of 54Mn incorporation than those on a normal diet. No difference in 54Mn incorporation was found in submaxillary glands from any of the groups studied. In brain tissue, 2 h after injection of l-dopa, the 54Mn radioactivity was the same in normal and manganese-loaded animals and significantly higher than in rats not given the amine. The reverse effect was found in serum which from l-dopa-treated rats showed lower radioactivity than the controls, suggesting an increased passage of the tracer to the tissues. The different response of tissues from manganese-loaded rats could mean that the enzyme adenyl cyclase may be affected by the excess of manganese. Since dopamine does not cross the blood brain barrier, the l-dopa increase of 54Mn uptake by brain could occur in the endothelial cells of the capillaries.
Multicomponent analysis of ultraviolet spectra: application to pharmaceutical dosage forms
Authors: Madsen B W , Robertson J S
Published: April 2011

Assay of sulphacetamide and physostigmine eye drops, sulphadi-midine and tri-sulphonamide tablets, and a triple barbiturate capsule has been possible without prior extraction or purification of the ingredients. Concentration estimates were found using the method of least squares, and safeguards were incorporated in the computer program to determine confidence levels. The method should be applicable to other agents and dosage forms and lend itself to automation.
Solute migration during granule drying
Authors: Rubinstein M H , Ridgway K
Published: April 2011

Spherical granules of magnesium carbonate, incorporating polyvinylpyrrolidone (PVP) as granulating agent, have been dried at various temperatures under controlled conditions in a drying tunnel. At each drying temperature the rate of loss of moisture was continuously recorded. The PVP distribution, modulus of elasticity, Brinell hardness and friability of the granules were measured as a function both of moisture content and of depth from the granule surface. The radial distribution of PVP at different stages of the drying process and at three drying temperatures, and its effect on the physical properties of the granules, were thus found. This gave a picture of binder distribution within the granule and its effect on local strength as drying occurred and also of the overall change caused by alteration in drying temperature.
Inhibitory effects of L-glutamine on the aspirin-induced gastric lesions in the rat
Authors: Okabe S , Takeuchi K , Nakamura K , Takagi K
Published: April 2011

The effects of an amino acid, L-glutamine, on aspirin-induced gastric lesions and gastric secretion were studied in either intact or pylorus-ligated rats. L-Glutamine had a pronounced inhibitory effect on gastric lesions induced by aspirin administered by oral, intraperitoneal, or intraduodenal routes to intact or pylorus-ligated rats. By the oral route the inhibition was dose-related. However, L-glutamine given either intraduodenally or intraperitoneally did not show any appreciable effects on gastric lesions induced by orally administered aspirin in pylorus-ligated rats. One mechanism of L-glutamine protection was inhibition of a back diffusion of gastric acid caused by aspirin and this was demonstrated in pylorus-ligated rats. The reduction in H+ and increase in Na+ concentrations in the lumen caused by aspirin was returned to normal by increasing doses of L-glutamine. In addition, L-glutamine was considered to inhibit the back diffusion of acid caused by pylorus ligation per se, because the amino-acid produced an increment of H+ and reduction of Na+ and K+ in comparison with the control group. The role of pepsin on L-glutamine protection was negligible.
Some pharmacological actions of 2,5-dimethoxy-4-ethylamphetamine (DOET) in rats and mice
Authors: Huang Jen-Tzaw , Ho Beng T
Published: April 2011

DOET, like DOM, exhibited pressor action in rats. This increase of blood pressure was blocked by pretreatment with cinanserin. DOET at high doses decreased the spontaneous locomotor activity of mice at the first hour but increased the activity at the second hour; a low dose was less effective. DOET also increased the rectal temperature of rats and this hyperthermic action was suppressed by pretreating the animals with cinanserin or methysergide. These actions of DOET were compared with those of DOM.
The effect of 5-hydroxytryptophan on food intake and on the anorexic action of amphetamine and fenfluramine
Authors: Blundell J E , Leshem M B
Published: April 2011

5-Hydroxytryptophan (5-HTP), amphetamine and fenfluramine suppressed food intake in normal rats and in animals with lesions of the lateral hypothalamus. The anorexic effect of amphetamine was reduced in lesioned animals compared with controls while the effect of 5-HTP like that of fenfluramine was increased. When administered in conjunction with the anorexic drugs, 5-HTP markedly potentiated the anorexic effect of amphetamine in both control and lesioned animals. However, 5-HTP potentiated fenfluramine anorexia only in lesioned rats. These findings provide further evidence for the role of 5-hydroxytryptamine (5-HT), in the anorexic effect of fenfluramine, and suggest that a 5-HT mechanism, inhibitory for feeding, produces particularly severe suppression of food intake in rats with lateral hypothalamic lesions.
Binding of chlorpromazine and imipramine to red cells, albumin, lipoproteins and other blood components
Authors: Bickel M H
Published: April 2011

The binding of model drugs to human blood and individual blood components has been determined by equilibrium dialysis and expressed in terms of classes of binding sites, association constants and binding capacities. Chlorpromazine and imipramine are bound to three major components: membranes of red cells, albumin, and lipoproteins. The affinity and capacity of lipoprotein binding is at least as high as that of albumin and is equally distributed on HDL, LDL, VLDL, and on the chylomicrons. White blood cells and platelets are of minor importance in terms of binding capacity. No binding was detected with γ-globulins or α- and β-globulins other than lipoproteins. In contrast, salicylic acid was not bound to red cells or lipoproteins.
The pharmacology of 14-hydroxyazidomorphine
Authors: Knoll J , Fürst Susanna , Makleit S
Published: April 2011

6-Deoxy-6-dihydroazido-14-hydroxyisomorphine (14-hydroxyazidomorphine) was synthesized, its analgesic potency in mice and rats, its antitussive effect in rats and its dependence liability in mice, rats and monkeys were studied. Azidomorphine, the 14-nonhydroxylated parent molecule, morphine, hydromorphone and oxymorphone were used for comparison. 14-Hydroxyazidomorphine proved to be as potent an analgesic as azidomorphine, even more potent as an antitussive, and showed the same low tolerance and dependence capacity. It was 11.6 times less toxic than azidomorphine in mice and 6.5 times less toxic in rats.
A simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in plasma by gas liquid chromatography
Authors: Rance Michael J , Jordan Bernard J , Nichols John D
Published: April 2011

A novel method for the simultaneous determination of acetylsalicylic acid, salicylic acid and salicylamide in biological fluids by gas liquid chromatography is described. The assay has been used to determine the plasma concentration of salicylates in 10 volunteers after oral ingestion of three commercially available aspirin-containing formulations. No difficulty was encountered in determining low concentrations of acetylsalicylic acid in the presence of higher concentrations of salicylic acid. The in vivo plasma half life of acetylsalicylic acid in man was found to be 15.5 min.
Synthesis and characteristics of the enantiomers of the cyclic metabonate of methadone
Authors: Beckett A H , Essien E E , Antiri-Penrose C
Published: April 2011

2-Ethylidene-l,5-dimethyl-3,3-diphenylpyrrolidine (II), a cyclic metabonate of methadone was synthesized from methadone (I) and methadone-N-oxide (III). m-Chloroperbenzoic acid was used to oxidatively demethylate I while sulphur dioxide reductively demethylated III to give II. The importance of these syntheses lies in the fact that there is no attack on the asymmetric carbon atom in I or III, thus providing direct methods of obtaining the optical isomers of II.
A comparison of solute migration in a test granulation dried by fluidization and other methods
Authors: Travers D N
Published: April 2011

The intragranular migration of sodium chloride in granules made by the wet massing of heavy kaolin B.P. with salt solution has been studied in batches dried by fluidization and a vacuum tumbling method. The larger granules from the fluidized batch exhibited considerable intragranular variation with the outer crust containing over twice the average salt concentration. Solute loss from this layer by abrasion on prolonged fluidization was slight but the dust eluted from the dryer had a salt content above average. Analysis of sieved fractions of the dust showed that this enrichment was concentrated in the fine material passing a 53 μm mesh. The vacuum dried granules had less migration and were less resistant to crushing than those dried by fluidization. The dust produced had a salt content only slightly greater than the average composition and the overall solute content of the sized fractions were all close to this average. The same system was used to study intergranular migration in a fixed bed when the granules were dried by infrared radiation, by microwave radiation, by convection from air and in a vacuum. The greatest migration occurred in samples dried by infrared radiation and the maximum solute concentration was near the middle of the bed. The air dried granules had less migration and the maximum concentration was in the surface layer. The granules dried in a vacuum and by microwave radiation were fairly uniform in composition throughout the bed. The above results are explained on the basis of the capillary theory of drying together with the modifying influence of the drying method on the probable heat and mass transfer rates.
Trialkylsilyl moieties as potential pharmacokinetic modifying groups for aminoalcohols
Authors: Beckett A H , Taylor D C , Gorrod J W
Published: April 2011

Water soluble derivatives of the aminoalcohols methylephedrine, ephedrine and norephedrine have been synthesized to contain various trialkyl silyl groups attached to the hydroxyl group of the aminoalcohol hydrochloride. Variation of the alkyl substituents on the silyl group produces a wide variety of derivatives possessing differing lipid solubilities and rates of hydrolysis to the parent aminoalcohol.
The percutaneous absorption of phenolic compounds: the effect of vehicles on the penetration of phenol
Authors: Roberts M S , Anderson R A
Published: April 2011

The effects of interactions between drug and skin, drug and vehicle, and vehicle and skin on the overall penetration rate of a drug through the skin may be evaluated by comparison of penetration rates through excised skin and an inert reference membrane such as polyethylene. Dimethyl sulphoxide, dimethyl formamide, ethanol and water increase the permeability of the skin but because of reduced thermodynamic activities in the vehicles low penetration rates are observed.
Enhancement of permeability of ethyl cellulose films for drug penetration
Authors: Donbrow M , Friedman M
Published: April 2011

Permeability constants of salicylic acid, caffeine and benzoic acid have been measured at 37° for heterogeneous films of ethyl cellulose containing up to 50% PEG 4000, the latter component undergoing leaching out. For the first two compounds, steady state constants were independent of film thickness and solute concentration but increased linearly and sharply with PEG content and were reproducible. The films were impermeable to NaOH and permeation rates were independent of receiver compartment pH. Solubility coefficients and diffusion coefficients of the substances in the films were measured using sorption and/or time lag methods and were low as compared with polyethylene films. High solubility seemed to be associated with the presence of a free activated hydrogen, shown by sorption studies on other substances. From the evidence, it appeared that mass transfer was controlled by the solubility diffusion process in the ethyl cellulose of the membranes with all three substances. Enhancement of permeability by PEG thus seemed due to increased porosity, equivalent to reduction in the effective thickness of the matrix, which nevertheless retained its barrier properties. Enhancement coefficients calculated from the slopes of PEG concentration plots may be useful for predicting the increased mass transfer of drugs through such membranes and could enable the porosity and thickness factors to be balanced against each other for formulation of coated products.
The metabolism of dibenzylamine: identification of NN-dibenzylhydroxylamine as the major in vitro metabolic product from rabbit fortified hepatic homogenates
Authors: Beckett A H , Coutts R T , Gibson G G
Published: April 2011

A study of the in vitro metabolism of dibenzylamine with fortified rabbit liver 9000 g supernatant fractions has shown that N-oxidation is the major metabolic process. Of the total amount of dibenzylamine metabolized, 90% is converted to NN-dibenzylhydroxylamine. The primary amine, benzylamine, is formed to the extent of only 6% of total substrate metabolized. The identity of the major metabolite, NN-dibenzylhydroxylamine has been established by thin-layer chromatography, gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry.
The interaction of antihistamines with lecithin monolayers
Authors: Attwood D , Udeala O K
Published: April 2011

The interaction of a series of antihistamines with monolayers of l-α-dipalmitoyl lecithin has been examined. An increase in the monolayer surface pressure was noted for monolayers spread on the antihistamine solutions, suggesting penetration of the film by drug molecules. At high surface pressures there was an apparent ejection of drug molecules from the film. The ability of the antihistamines to increase surface pressure was correlated with their surface activity at the air-solution interface. The effect of drug concentration on the magnitude of the surface pressure was examined for diphenhydramine hydrochloride. Application of the Gibbs adsorption equation at low surface compressions indicated an approximate area per molecule for diphenhydramine in the film which was in good agreement with the value previously obtained at the air-solution interface. Preliminary measurements showed that the surface pressure increase was larger in the presence of phosphate buffer at pH 6·8. It was not clear whether this effect was caused by the buffer components or was a pH effect.
Phenylbutazone-warfarin interaction in the dog
Authors: Bachmann K A , Burkman A M
Published: April 2011

The administration of phenylbutazone together with warfarin to dogs resulted in an elevation of the free fraction of warfarin in the plasma from 2·6 to 8·0% thus providing direct support for the notion that phenylbutazone induced inhibition of warfarin binding to plasma proteins. This inhibition as evaluated by a kinetic method was accompanied by a two-fold decrease in the plasma half-life of warfarin from 18·4 h in control animals to 9·6 h in phenylbutazone-treated animals. Marked increases in warfarin-induced hypoprothrombinaemia were observed when at doses up to 8 mg kg−1 (orally) it was given with phenylbutazone (50 mg kg−1, orally). The unbound fraction of warfarin in canine plasma ranged from 1·7 to 4·3% indicating individual differences in the extent of the plasma binding of warfarin in the dog.
The effect of pancuronium on myocardial contraction and catecholamine metabolism
Authors: Ivankovich A D , Miletich D J , Albrecht R F , Zahed B
Published: April 2011

The effects of pancuronium bromide infusion on the uptake and release of [14C] noradrenaline (14C-NA) by the isolated, perfused rat heart and on the chronotropic and inotropic activity of the isolated heart were evaluated. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min−1. The effect of pancuronium on the uptake of noradrenaline was determined by perfusing hearts for 5 min with perfusate containing various concentrations of pancuronium and 200 ng ml−1 of 14C-NA. After 5 min pancuronium-treated hearts contained less 14C-NA. The degree of reduced uptake increased with increasing concentrations of pancuronium. In addition, the combination of pancuronium perfusion and electrical stimulation (15 mA for 10 ms at 4 Hz) blocked the 50 min uptake of 14C-NA by the heart to a greater degree than either factor separately. The release of noradrenaline was determined after perfusing hearts with 14C-NA followed by perfusion with solution containing pancuronium but no 14C-NA for 1 h. Pancuronium infusion did not significantly alter the release of 14C-NA from the heart after 1 h of perfusion. The infusion of pancuronium caused a reduction in both the rate and strength of myocardial contraction of the isolated heart which was reversed by perfusion with perfusate free of pancuronium. Following perfusion with pancurnium the rate and strength of contraction of the heart was seen to “rebound” above pre-pancuronium values for a short period. The rebound of myocardial rate and contraction may have been due to the presence of myocardial noradrenaline previously blocked from reuptake by pancuronium since hearts removed from reserpinized animals did not demonstrate “rebound.”
Cornea preparation for in vitro biopharmaceutical evaluation of ophthalmic dosage forms
Authors: Barrelet J , Tsacopoulos M , Buri P
Published: April 2011

A system has been developed for a specific biopharmaceutical purpose: testing, for ophthalmic preparations, the influence of formulation on drug transport through the cornea. The apparatus is a lucite cell, divided in two compartments by a clamped rabbit cornea. Physiological conditions are ensured by a supply of oxygenated perfusion medium. They are monitored by electrical conductivity and corneal thickness measurements. Reliability of the system was tested in a set of experiments.
Comparison of the nuclear magnetic resonance and infrared spectroscopic methods for the quantitative analysis of polydimethylsiloxane
Authors: O’Neill I K , Pringuer M A , Prosser H J
Published: April 2011

A method based on nuclear magnetic resonance spectroscopy is described for the quantitative determination of polydimethylsiloxane (PMS) in a variety of pharmaceutical preparations. An extraction procedure using deuterochloroform within the sample tube was devised. In the presence of an internal standard, the PMS concentration was determined directly using integrated peak areas, without the necessity of establishing calibration curves. Accurate quantitative results were achieved with samples containing at least 2mg PMS, extracted from formulations containing greater than 0.5% PMS. The extraction procedure and nmr assay were both more efficient and convenient than the B.P.C. method.
The role of dopamine and noradrenaline in temperature control of normal and reserpine-pretreated mice
Authors: Cox B , Tha S J
Published: April 2011

Drugs with the common property of stimulating dopamine receptors, have been tested for their effects on core temperature in control and reserpine-pretreated mice. Apomorphine, amantadine, amphetamine, L-dopa and atropine all produced a fall in mouse oesophageal temperature, their efficacy correlating with their ability to activate central dopamine receptors. Amphetamine and L-dopa had a biphasic effect the initial fall being followed by a rise. In reserpine-pretreated mice only amphetamine, apomorphine, L-dopa and D,L-threo-dihydroxyphenyl-serine effectively reversed the hypothermia. Amphetamine had the highest efficacy of all the drugs tested. The sum of the effects of apomorphine and D,L-threo-dihydroxyphenyl-serine was equivalent to the effect of amphetamine alone. It is suggested that in control mice dopaminergic mechanisms mediate the hypothermia and noradrenergic mechanisms the hyperthermia. In reserpine-pretreated mice both systems are involved in the mechanisms restoring body temperature to normal.
Release of adrenaline by anaphylaxis in the guinea-pig: its effect on lung lipid content
Authors: Goadby P
Published: April 2011

The study was undertaken to discover whether the catecholamines released as a result of the stress and hypoxia of anaphylaxis were responsible for the concomitant loss of lipid from the lung. A method is described whereby the respiratory rate and volume and heart-rate of conscious sensitized guinea-pigs were measured and the electrocardiogram recorded during anaphylaxis induced by aerosolized antigen. After 7 days or more, some animals were anaesthetized with pentobarbitone and respiration was artificially maintained at the level recorded in the conscious state, whilst the quantity of catecholamines liberated during anaphylaxis was assayed using an extracorporeal blood circulation to superfuse smooth muscle preparations. In other animals of the same group, it was shown that intravenous infusion of adrenaline in a similar quantity to that detected in the circulation following anaphylaxis (0.3 μg min−1 for 40 min) caused losses of triglyceride and partial glycerides from the lungs. Thus, the loss of choline-containing phospholipid was attributed to the direct effects of the anaphylactic reaction on the lung tissue.
The effect of some polyene macrolides on absorption from the small intestine in the rat
Authors: English J , Chakraborty J , Marks V
Published: April 2011

The effect of three polyene macrolides, candicidin, amphotericin B and nystatin on the absorption of [3H]cholesterol was studied in the rat by using the in situ gut loop perfusion technique. Chronic treatment with candicidin and its presence at various concentrations in the gut loop perfusion experiments inhibited [3H]cholesterol absorption although a smaller effect was also obtained with amphotericin B and nystatin at higher concentrations. A similar but much less pronounced action of candicidin was also observed on the absorption of [3H]corticosterone and [14C]phenytoin.
The influence of casting solvent composition on structure and permeability of acrylic-methacrylic ester copolymer films
Authors: Abdel-Aziz S A M , Anderson W
Published: April 2011

Decrease in the solvation of polymer by inclusion of ethanol in the acetone casting solution resulted in greater permeability to urea of cast acrylate-methacrylate film. The greater permeability was accompanied particularly by a decrease in pore size and increase in pore number, despite the absence of change in pore area. A decrease in cohesiveness in the film was suggested by the decrease in tortuosity of the pores as seen by scanning electron microscopy; also, water uptake was increased when the film was cast from an ethanolic solution. The results support the view that, in practice, the composition of the solvent, by its effect on microstructure, can affect the function of the film cast from it.
A simple technique for the frequent intravenous infusion of fluid without heparin into the rabbit
Authors: Bowyer D E , Reidy M A
Published: April 2011

A technique is described for the daily intravenous injection over 16 weeks in the rabbit. The system consists of a Teflon cannula passed down the external jugular vein with the tip in the superior vena cava. The cannula is joined at the point of entry to the jugular vein to a length of silicon rubber tubing, which is then passed subcutaneously to the forehead. The silicon tubing is terminated on a Luer needle hub, which is held in a simple Perspex plate secured subcutaneously between the rabbit's ears. The Luer hub is covered with a replaceable rubber cap through which injections may be made. With this system cannulae were maintained patent for 16 weeks by flushing once a day with Hanks' balanced salt solution, pH 7·4.
Reversed ester analogues of pethidine: isomeric 4-acetoxy-1,2,6-trimethyl-4-phenyrpiperidines
Authors: Casy A F , Coates J E , Rostron C
Published: April 2011

The preparation and stereochemical characterization of all three isomeric forms of 4-acetoxy-1,2,6-trimethyl-4-phenylpiperidine is described. Of these, only the t-2-Me,c-6-Me,r-4-OCOMe isomer was an effective analgesic in mice (2·3 × pethidine) as judged by the hot-plate test. The results, together with reported data, demonstrate the potency raising effects of axial methyl α- to nitrogen and the lowering action of equatorial α-methyl substituents in reversed esters of pethidine.
Gastrointestinal absorption of carbenoxolone in the rat determined in vitro and in situ: deviations from the pH-partition hypothesis
Authors: Bridges J W , Houston J B , Humphrey M J , Lindup W E , Parke D V , Shillingford J S , Upshall D G
Published: April 2011

The absorption of [14C] carbenoxolone from everted rat ileum in vitro and from rat stomach and ileum in situ has been examined. The rate of its mucosal to serosal transfer in vitro increases as pH increases from 5 to 8 whereas the amount bound to ileum tissue decreases with increased pH; absorption closely parallels the drug's solubility. The uptake of carbenoxolone in situ is bi-exponential and the rate constants for the two processes, have been calculated. Absorption in situ, and biliary excretion, of the drug increases with increasing pH from 5·0 to 7·4. Tissue binding to the ileum in situ is not dependent on pH except below pH 5·0 when extensive tissue accumulation of carbenoxolone occurs because of its low solubility. Tissue binding to the stomach increases markedly with decrease of pH from 7·4 to 6·5 and at pH 6·5 is 80 times greater than binding to the intestine. The rate of absorption from the stomach, at pH 6·5–7·4, was much less than that from the intestine in situ. When allowance is made for the binding of carbenoxolone to the stomach, contrary to the pH-partition hypothesis, correlation is apparent between its absorption and the amount present in the ionized form.
Some pharmacological properties of the venom, venom fractions and pure toxin of the yellow-bellied sea snake Pelamis platurus
Authors: Tu Tsuchih , Tu Anthony T , Lin Tzu-Shen
Published: April 2011

The effects of the crude venom, four partially purified venom fractions and pure toxin (Pelamis toxin a) from yellow-bellied sea snake, Pelamis platurus, on respiration, blood pressure, heart and skeletal muscle of rabbits have been examined. Results indicated that crude venom, a partially purified toxic fraction and Pelamis toxin a caused initial respiratory stimulant effects followed by respiratory paralysis. In most cases, respiratory paralysis occurred before a profound fall in arterial pressure. Depression of the twitch response to nerve stimulation was observed in the tibialis anterior muscle. No significant change in the electrocardiogram was seen. Three partially purified non-toxic fractions of the crude venom induced transient respiratory stimulant effects. It was concluded that the crude venom and Pelamis toxin a had an identical mode of action and that they caused respiratory paralysis in rabbits.
Oxytetracyline tablet formulations: effect of variations in binder concentration and volume on granule and tablet properties
Authors: Chalmers A A , Elworthy P H
Published: April 2011

Formulation studies have been conducted on an oxytetracycline dihydrate tablet formulation containing microcrystalline cellulose and alginic acid, wet granulated with polyvinylpyrrolidone (PVP) solution. A range of granule properties including size, strength, packing and porosity, and tablet properties including breaking load, porosity, disintegration and dissolution have been measured. Increased compaction pressure decreased tablet porosity. The reproducibility of the above properties was determined by tests on nine standard batches of granules and tablets. An increased concentration of PVP in the binder solution decreased the rate of tablet dissolution. Although the volume of granulating solution apparently controlled the granule size, it did not significantly alter the tablet dissolution, when the amount of PVP was constant.
The crystallization behaviour of sulphathiazole
Authors: Jordan D , Carless J E
Published: April 2011

Previous investigations into the dissolution kinetics of sulphathiazole Form 1 have shown the process to be first order with respect to driving force. However, below 37° first order kinetics did not apply, due to the surface reaction becoming the rate controlling factor. The present study examines the kinetics of crystallization over the temperature range 25 to 50°. Crystallization is a process greatly dependent upon the high-entropy surface integration step which, unlike the dissolution process, is much more sensitive to crystal growth inhibitors. In the absence of inhibitors crystallization above 34° follows first order kinetics but below 34° the process changes to third order. Similar temperature effects on the dissolution of sulphathiazole have been previously reported.
Acute anti-inflammatory effects of aspirin and dexamethasone in rats deprived of endogenous prostaglandin precursors
Authors: Bonta I L , Bult H , Vincent J E , Zijlstra F J
Published: April 2011

Paw oedema, induced by carrageenan, was potentiated in normal rats by arachidonic acid and bishomo-γ-linoleic acid, but not by 5,8,11-eicosatrienoic acid. The latter is not an endogenous prostaglandin precursor, but replaces the other two in essential fatty acid deficient (EFAD) rats. Carrageenan oedema was partially suppressed in these EFAD rats. Aspirin exhibited equal suppression of carrageenan oedema in both normal and EFAD rats, despite the fact that, in the latter, prostaglandins are of negligible importance. The anti-inflammatory effect of dexamethasone was also identical in both normal and EFAD rats. The view that interference with the prostaglandin-system explains the acute anti-inflammatory effects of the two drugs, is discussed, in relation to the present results.
The effect of compression on some physical properties of microcrystalline cellulose powders
Authors: Sixsmith David
Published: April 2011

Tablets have been prepared from previously characterized microcrystalline cellulose (Avicel) powders, using an instrumented single station tablet machine. The regenerated particle size was found to increase with increase in compaction pressure. Compaction caused a slight initial decrease in B.E.T. surface area, followed by an increase mainly as a result of elastic recovery of the particles. The intra-particulate pore size distribution showed no change throughout the range of compaction pressures studied, demonstrating that the internal pores did not collapse. Measurement of the interparticulate porosity by mercury porosimetry, liquid penetration techniques and scanning electron microscopy showed a decrease in this parameter with increase in compaction pressure. The dissolution behaviour from the compacts showed in general a decreased rate with increase in compaction pressure, that from the cellulose grade PH 105 being slower than from the remaining grades.
Dimensional changes of compacts after compression
Authors: York P , Baily E D
Published: April 2011

A non-contact optical technique has been used to measure changes in the heights and diameters of compacts prepared from sodium chloride, spray dried lactose, two samples of methylcellulose powder and two spray-dried lactose-maize starch granulations. Both sodium chloride and spray dried lactose exhibited relatively small dimensional changes whilst the methylcellulose powders showed up to 30% axial and 3% radial expansion. The results are discussed in terms of the inherent properties of the materials. When the lactose was granulated with maize starch, the ratio of axial: radial strain recovery was reduced from 5·9:1 to approximately 1:1, suggesting an improved distribution of forces during compression of the granulations.
The influence of temperature on the sorption of benzocaine by nylon 6 from aqueous cosolvents
Authors: Richardson N E , Meakin B J
Published: April 2011

The influence of temperature on the sorption of benzocaine by nylon 6 powder from aqueous cosolvents has been assessed. At about 30° discontinuities appear in the Van't Hoff plots for sorption from water and aqueous PEG 400, which may be attributed to transitional changes in the polymer structure. No such discontinuities are apparent for sorption from aqueous ethanol over the temperature range 15–60°, which is indicative of plasticization by this cosolvent.
The fate of prostaglandin A1-5,6-3H in the rat
Authors: Sinha A J Wickrema , Shaw S R
Published: April 2011

The plasma concentrations, tissue distribution and excretion of prostaglandin A1 (PGA1) and related metabolites have been determined in rats, following the intravenous injection of a single dose of PGA1-5,6-3H. Urinary and faecal excretion accounted for averages of 25 and 43%, of the administered dose of PGA1, respectively. Oxidative cleavage of the carboxyl side chain of PGA1 appeared to be a major metabolic pathway in the rat. PGA1-5,6-3H was deemed unsuitable for metabolism studies in man, in view of the significant loss of tritium label from the prostaglandin.
The effect of some binding agents on the mechanical properties of granules and their compression characteristics
Authors: Doelker E , Shotton E
Published: April 2011

The modulus of elasticity and the crushing strength of cylindrical granules prepared by a template method, and the friability of conventional granules were measured and the effect of the binding agents, PVP, methyl cellulose and maize starch examined. These properties were related to the compression characteristics of the granules and to the crushing force of the subsequent tablets. According to the base material two cases were observed. With dicalcium phosphate little plastic flow was evident and low radial stress transmission was noticed, the softest granules led to the weakest compacts. With paracetamol more plastic flow occurred giving a greater axial to radial conversion of force and the softest granules produced the strongest tablets. The extent of further generated contact area played the major role. Generally, due to the better bonding capacity, dicalcium phosphate gave stronger compacts than paracetamol, although lower radial transmission ratios were recorded. A good conversion of axial to radial force was thus proved not to be the main factor in obtaining good tablets, as was also confirmed by the paracetamol powder alone. With paracetamol the residual pressure on the die wall was greater with the formulations producing satisfactory tablets than with paracetamol alone which gave rise to capping.
Derivatization to stabilize some aliphatic primary hydroxylamines for g.l.c. analysis
Authors: Beckett A H , Achari R
Published: April 2011

By appropriate choice of trimethylsilylating and trifluoroacetylating reagents and organic solvents for extraction, stable derivatives of aliphatic primary hydroxylamines metabolites, N-hydroxyphentermine, N-hydroxychlorphentermine, N-hydroxymexiletene, N-hydroxy-phenethylamine, N-hydroxyamphetamine, and N-hydroxy-3,4-dimethoxyamphetamine, were obtained and examined by g.l.c. analysis without decomposition and without interference from the parent drug or other metabolic products.
The enkephalins and opiates: structure-activity relations
Authors: Horn Alan S , Rodgers John R
Published: April 2011

The X-ray structures of 9 ‘opiate’ drugs which exhibit a range of pharmacological activity have been examined in detail leading to the theory that one of the reasons why the enkephalins and related peptides possess morphine-like activity is because they have a tyrosine, and hence a ‘tyramine’, residue at the amino terminal position. This residue or a conformationally similar moiety, can be shown to be present in many opiates and analogues.
The effects of etilefrine on blood vessels in the rat tail
Authors: Frost B R , Frewin D B , Gerke D C
Published: April 2011

Etilefrine was found to constrict blood vessels in the rat tail through a mechanism which was partly dependent on the sympathetic nerves present in these vessels. The response to the drug was enhanced by pretreatment with noradrenaline and cocaine, and totally abolished by the α-receptor antagonist phentolamine. When compared with several other sympathomimetic agents which were tested on the vessel, etilefrine appeared to have a low order of vasoconstrictor activity. These findings would seem to have considerable relevance to the clinical situation where an attempt has been made to use etilefrine in the treatment of patients with orthostatic hypotension.
The identification and analysis of mexiletine and its metabolic products in man
Authors: Beckett A H , Chidomere E C
Published: April 2011

Sensitive and specific gas-liquid chromatographic methods were developed for the analysis of mexiletine and its metabolites in urine of man. The identity of the g.l.c. peaks was established by mass-spectrometry. The hydroxylamine (Va) was qualitatively identified and determined quantitatively after conversion to the more stable oxime (Vb). Selective extraction procedures, t.l.c. and derivatization with hexamethyldisilazane (HMDS) and trifluoroacetic anhydride (TFA) were used in the qualitative identification of the major metabolites (VI-IX), particularly in distinguishing the basic products VI and VII from their corresponding alcoholic products VIII and IX. The limit of detection of the g.l.c. method was 6 to 12 ng ml-1 for compounds I-IV, and 40 to 50 ng ml-1 for compounds Vb-IX.
The effect of temperature on the tensile strength and disintegration of paracetamol and oxytetracycline tablets
Authors: Pilpel N , Esezobo S
Published: April 2011

The tensile strengths and disintegration times of paracetamol and oxytetracycline tablets at room temperature are higher when they have been prepared at high temperatures, e.g. 85°, than at room temperature or below, e.g. —20°. The activation energies of the two materials, 3 and 1 k cal mol−1 (13 and 4 kJmol−1) respectively, were derived from plots of log tensile strength and log disintegration time versus the reciprocal of the absolute temperature. The results have been explained in terms of sintering theory and the formation of welded bonds between particles.
The release of plasticizer from polyvinyl chloride haemodialysis tubing
Authors: Fayz S , Herbert R , Martin A M
Published: April 2011

The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached.
Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats
Authors: Braestrup C
Published: April 2011

Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The ‘methylphenidate group’ also increased brain 3,4-dihydroxy-phenylacetic acid (DOPAC) in naive rats; whereas the ‘(+)-amphetamine group’ decreased DOPAC in naive rats, as well as in reserpinized rats, α-methyl-p-tyrosine-treated rats, and after acute hemisection. The reserpine antagonism of the ‘methylphenidate group’-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The ‘(+)-amphetamine group’-induced stereotyped behaviour was not blocked by short time pretreatment with α-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the ‘(+)-amphetamine group’.
Neurochemical correlates of ethanol withdrawal: alterations in serotoninergic function
Authors: Tabakoff Boris , Hoffman Paula , Moses Frances
Published: April 2011

Cessation of chronic ethanol administration, and elimination of ethanol from the body, results in a withdrawal syndrome in mice characterized by behavioural symptoms and hypothermia. During withdrawal, the accumulation rate of [14C] 5-hydroxytryptamine (5-HT) from [14C]tryptophan, was significantly lower in the brainstem of the ethanol-withdrawn animals than in controls. A similar pattern was seen in forebrain. When the rate of 5-HT accumulation was determined using pargyline, no differences occurred between control and ethanol-treated animals. The endogenous concentrations of tryptophan in plasma, and tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain were the same in ethanol-treated and control animals. It is suggested that the changes in accumulation of 14C-5-HT and 14C-5-HIAA in ethanol-withdrawn animals reflected alterations in electrical activity of serotoninergic neurons during withdrawal.
Neutral in vivo metabolites of cannabinol isolated from rat faeces
Authors: Yisak Wolde-Ab , Marianne  , Widman  , Lindgren Jan-Erik , Agurell Stig
Published: April 2011

The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono-oxygenated and dioxygenated CBN metabolites have been identified. In the mono-oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7-hydroxy-CBN, 4“-hydroxy-CBN, 1”-hydroxy-CBN, 2“-hydroxy-CBN, 3”-hydroxy-CBN, 5“-hydroxy-CBN and CBN-7-al. In the dihydroxylated metabolite series only 1”,7-dihydroxy-CBN and 4“,7-dihydroxy-CBN were found with the former as the more prominent metabolite.
Influence of pyridylisatogen tosylate on contractions produced by ATP and by purinergic stimulation in the terminal ileum of the guinea-pig
Authors: KaẐIĆ T , MilosavljeviĆ D
Published: April 2011

2-2′Pyridylisatogen tosylate (PIT), which antagonizes the inhibitory action of ATP in the taenia caeci, did not antagonize the excitatory effects of exogenous ATP and of purinergic stimulation of the terminal guinea-pig ileum. PIT (0·5–2·5 μm) potentiated the ATP-induced contractions and also the contractions produced by potassium chloride, though the potentiation could not be related to the dose in every experiment. The responses to noradrenaline, adrenaline and histamine were slightly inhibited. PIT also potentiated the contractions produced by electrical stimulation of intramural purinergic nerves when either an alternate or uniform stimulation pattern was used. The present results in which the preparation is contracted by ATP are opposite to those obtained with PIT on the taenia caeci, which is relaxed by ATP. This raises a question of duality or plurality of receptors for ATP.
A sex difference in the interaction between promethazine and morphine in the mouse
Authors: Shater H A O , Pleuvry Barbara J
Published: April 2011

The effects of promethazine on the antinociceptive and respiratory actions of morphine have been examined in the mouse. Moderate doses of promethazine (5 and 10 mg kg−1) potentiated morphine's action in male mice but inhibited it in female mice. Gonadectomy abolished the interaction between promethazine and morphine in both sexes, although the intensity and duration of morphine's activity was greatly enhanced in these mice. Replacement of oestradiol in ovariectomized mice restored morphine's activity to intact female control values. However, interactions between promethazine and morphine required progesterone, as well as oestradiol, replacement to obtain results approaching those obtained in intact female mice.
The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart
Authors: Corte Laura Della , Callingham B A
Published: April 2011

The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.