bluuebunny/crossref_metadata_2025 huggingface dataset:
The quantitative measurement of motor inco-ordination in naive mice using an accelerating rotarod
Authors: Jones B J , Roberts D J
Published: April 2011

A simple modification of the standard rotarod apparatus is described which eliminates the necessity of time-consuming training and consequently gives a truer measure of motor co-ordination since any effects on memory are avoided. The sensitivity and reproducibility of the procedure are much greater than those obtained with constant speed rotarods and less animals are required to obtain statistically significant results.
The stability of sucrose monolaurate: Rate of formation of lauric acid
Authors: Anderson R A , Polack A E
Published: April 2011

At concentrations below the critical micelle concentration, sucrose monolaurate hydrolyses to give lauric acid at first-order rates. At concentrations above the critical micelle concentration first-order kinetics are not obeyed. In systems buffered to pH values sufficiently high for the liberated lauric acid to ionize, the laurate ions appear to form mixed micelles with the ester and these carry negative charges. Coulombic repulsion of hydroxyl ions by these negative charges protects neighbouring ester molecules from attack and so reduces hydrolysis rates.
The effects of drug-induced adrenocortical deficiency and of mineralocorticoid drugs on anaphylaxis in the guinea-pig
Authors: HICKS R
Published: April 2011

Administration of adrenocortical inhibitors [metyrapone, amphenone-B, or 1,1-dichloro-2,2-di(p-chlorophenyl)ethane (DDD)] decreased anaphylactic preconvulsion times in guinea-pigs. Simultaneous corticotrophin treatment potentiated the effect of metyrapone. Metyrapone induced adrenocortical deficiency, and changed the character of corticosteroid secretion from predominantly glucocorticoid to mineralocorticoid. Mineralocorticoid treatment decreased preconvulsion times. Mepyramine prevented the effect of mineralocorticoids on anaphylaxis but did not modify the effect of metyrapone which probably resulted from glucocorticoid lack, but mineralocorticoid secretion may have contributed. Mineralocorticoids probably potentiated the histaminic component of anaphylaxis.
The colloidal properties of chlorhexidine and its interaction with some macromolecules
Authors: Heard D D , Ashworth R W
Published: April 2011

Surface tension, conductivity and dye solubilization experiments show that, in aqueous solution, chlorhexidine diacetate forms micelles and has a molar critical micellar concentration (CMC) of 0·010–0·011 at 25°. Similarly, the digluconate salt has a molar CMC of 0·0066. Above its CMC, the freely soluble digluconate salt solubilizes the less soluble diacetate salt. The formation of micelles does not affect the rate of hydrolysis of chlorhexidine to p-chloroaniline. It is suggested that the micelles formed by chlorhexidine resemble those formed by many dyes rather than those of colloidal surfactants. Equilibrium dialysis experiments show that 1·0 and 3·0% polysorbate 80 inactivates 37·5 and 70·0% respectively of the chlorhexidine in a 0·10% solution of the diacetate salt.
Gelatin coacervate microcapsules containing sulphamerazine: Their preparation and the in vitro release of the drug
Authors: Nixon J R , Khalil Saleh A H , Carless J E
Published: April 2011

An improved method is described for the preparation of gelatin coacervate microcapsules containing sulphamerazine as a fine deflocculated powder. The factors which control both the coacervation step and the recovery of the microcapsules are discussed. The in vitro release of sulphamerazine from microcapsules of different wall thickness which had been hardened by formaldehyde under different conditions has been studied. The method of preparation gave a high percentage of encapsulated material in comparison with other recovery techniques.
Interactions of narcotic antagonists and antagonist-analgesics
Authors: Blane G F , Dugdall D
Published: April 2011

In the rat the potent narcotic antagonist N-cyclopropylmethyl-6,14-endoethano-7α- (1-hydroxy-1-methylethyl)-tetrahydronororipavine (M5050, Reckitt), which itself lacks analgesic activity, resembled naloxone in its capacity to reverse the antinociceptive effects of morphine antagonist-analgesics. The nociceptive stimulus employed was bradykinin administered by an intra-arterial route. ED50 values were established for the reversal by M5050 of the analgesic effect of nalorphine, levallorphan, pentazocine and some newer compounds. When antagonist-analgesics were given concomitantly with morphine the response varied from antagonism of the analgesic effect of the morphine to synergism, depending on the dose combination.
The effect of antirheumatic drugs on the extractable collagen in lathyric chick embryos
Authors: Trnavský K , Trnavskñ Z
Published: April 2011

The lathyrogenic effect of 2·5 mg of β-aminopropionitrile in the chick embryo has been measured by the increase in the extractability of collagen from bones using M saline. Sodium salicylate (3 mg/embryo) and hydrocortisone (1·5 mg/embryo) applied 24 hr after the injection of β-aminopropionitrile decreased the elevated amount of soluble collagen. Phenylbutazone, chloroquine diphosphate and sodium aurothiosulphate were ineffective in this experimental system.
Subcellular distribution of [3H]amphetamine and [3H]guanethidine and their interaction with adrenergic neurons
Authors: Obianwu H O , Stitzel R , Lundborg P
Published: April 2011

The subcellular distribution of [3H]amphetamine and [3H]guanethidine and their interaction with each other and with noradrenaline binding sites have been examined. The ratio p/(p + s) × 100, an indication of affinity for noradrenaline storage particles, for [3H]amphetamine and [3H]guanethidine was 12% and 57% respectively. Protriptyline, a substance which inhibits amine transport mechanism at the level of the cell membrane, i.e. the membrane pump, and reserpine, an agent which impairs incorporation of amines into the storage particles in the adrenergic nerve fibre, inhibited the uptake and storage respectively, of [3H]guanethidine more than that of [3H]amphetamine. Retention of [3H]guanethidine by rat salivary glands was markedly decreased by sympathetic denervation of the glands while that of [3H]amphetamine was not. The results suggest that guanethidine possesses a much higher affinity for noradrenaline binding sites than amphetamine.
Activity of centrally acting drugs on amphetamine metabolism
Authors: Valzelli L , DOLFINI E , Tansella M , Garattini S
Published: April 2011

Amitriptyline, nortriptyline and dibenzepine prolong the increase in temperature produced by amphetamine in rats and also increase the level of brain amphetamine above that effected by amphetamine alone. After chlorpromazine and propericiazine, brain amphetamine levels are also higher but the rise of body temperature elicited by amphetamine is inhibited. Phenelzine prolongs and α-methyl-p-tyrosine inhibits the rise in body temperature without modifying the accumulation of brain amphetamine. In reserpinized rats amphetamine causes a temperature increase several degrees greater than in control animals although its level in the brain is lower.
The effects of diethyldithiocarbamate and L-dopa on body temperature in mice
Authors: Barnett A , Taber R I
Published: April 2011

Diethyldithiocarbamate (ddtc) raises body temperature in reserpinized mice, an effect that is unlikely to be an intrinsic action of the compound since ddtc lowers temperature in normal mice. ddtc has no effect on body temperature of reserpinized rats. The effects of ddtc on body temperature in normal and reserpinized mice are mimicked qualitatively by l-dopa indicating that the effects may reflect increased dopamine levels. Pargyline pretreatment does not influence the hypothermia produced by ddtc.
The role of the tissues and gut micro-organisms in the metabolism of [14C]protocatechuic acid in the rat. Aromatic dehydroxylation
Authors: Dacre J C , Williams R T
Published: April 2011

The fate of oral doses (0·1 g/kg) of [carboxy-14C]3, 4-dihydroxybenzoic (protocatechuic) acid in normal and neomycin-treated rats has been studied. In normal rats about 72% of the dose of 14C is excreted in 7 days (about 64% in urine and 8% in faeces) whereas in neomycin-treated rats 99% is excreted (87% in urine and 12% in faeces). In normal rats, the radioactive metabolites found in the urine excreted in 24 hr after dosing were protocatechuic acid (36%), vanillic acid (21%), m-hydroxybenzoic acid (2·1%), p-hydroxybenzoic acid (1·2%) and m-methoxybenzoic acid (2%). After neomycin-treatment protocatechuic acid (55%) and vanillic acid (22%) were found, but the other three were virtually absent. Incubation of [14C]protocatechuic acid with rat intestinal contents yielded 14CO2 and small amounts of m- and p-hydroxybenzoic acid. When [14C]protocatechuic acid was injected intraperitoneally into biliary cannulated rats about 13% appeared in the bile mainly as the 4-O-glucuronide of vanillic acid. It is concluded that, whilst the conjugation and methylation of protocatechuic acid occurs in the tissues of the rat, the dehydroxylation and decarboxylation of the acid is carried out by the gut micro-organisms.
The role of the tissues and gut flora in the metabolism of [14C]homoprotocatechuic acid in the rat and rabbit
Authors: Dacre J C , Scheline R R , Williams R T
Published: April 2011

The fate of orally administered [carboxy-14C]3, 4-dihydroxyphenylacetic (homoprotocatechuic) acid has been studied in normal and neomycin-treated rats and rabbits. In normal rats about 93% of the dose (0·1 g/kg) is excreted in 13 days after dosing, although 80% is excreted in the urine within 2 days. In neomycin-treated rats 100% of the 14C is excreted in 13 days, 95% being in the urine within 2 days. The urinary metabolites in 44 hr in normal rats were unchanged homoprotocatechuic acid (55% of the dose), homovanillic acid (19%), m-hydroxyphenylacetic acid (6·5%) and p-hydroxyphenylacetic acid (1·4%). In neomycin-treated rats, homoprotocatechuic acid (70%) and homovanillic acid (22%) were found but the other two metabolites were virtually absent. In normal and neomycin-treated rabbits, the 14C was excreted in the urine almost quantitatively in 9 days. The same metabolites as in rats were excreted, but there was more m-hydroxybenzoic acid (14%) and less homovanillic acid (6%). In neomycin-treated rabbits the excretion of m- and p-hydroxyphenylacetic acids was suppressed. In the rat, the metabolism of homoprotocatechuic acid, as far as methylation, dehydroxylation and decarboxylation (Scheline, 1967) is concerned, is qualitatively similar to that of protocatechuic acid (Dacre & Williams, 1968). In the rabbit, however, there is little, if any, decarboxylation. Whilst methylation is a reaction of the tissues, dehydroxylation and decarboxylation appear to be carried out by gut micro-organisms.
Effect of crystal form, cortisone alcohol and agitation on crystal growth of cortisone acetate in aqueous suspensions
Authors: Carless J E , Moustafa M A , Rapson H D C
Published: April 2011

Particle size distribution in aqueous suspensions of stable and unstable crystal forms of cortisone acetate under conditions of agitation and different degrees of saturation with cortisone alcohol is described. Agitation accelerated the diffusion-controlled processes of dissolution and crystallization, leading to the formation of a high proportion of large particles. Cortisone alcohol inhibited the polymorphic transformation necessary for the crystal growth and formation of the water-stable form. The mechanism of action is discussed.
The constituents of the seeds of Asphodelus microcarpus Viviani and A. fistulosus L.
Authors: Fell K R , Hammouda F M , Rizk A M
Published: April 2011

Evidence is presented that β-sitosterol and β-amyrin can be separated from the fixed oil of seeds of A. microcarpus Viviani and A. fistulosus L. by thin-layer, column and gas-liquid chromatography, together with other minor sterols (campesterol and stigmasterol). Myristic, palmitic, stearic, oleic and linoleic acids were identified in the oil of both species by thin-layer and gas-liquid chromatography. Sucrose, raffinose and stachyose were indicated in seeds of both species, also melibiose in seeds of A. microcarpus. Colchicine was not found in either species.
The uptake and retention of [3H]noradrenaline in rat sciatic nerves after ligation
Authors: Dahlström Annica , Waldeck Bertil
Published: April 2011

The uptake and retention of [3H]noradrenaline (3H-NA) was examined in sciatic nerves of albino rats. In the 1 cm part of nerve proximal to a 12 hr ligation the uptake and retention of exogenous noradrenaline was about 4 times the uptake in 1 cm of normal unligated nerves. Treatment with reserpine 10 hr before killing caused a marked decrease in the estimated amount of 3H-NA, while injection of nialamide 15 min before 3H-NA administration in ligated, reserpine-treated animals caused a somewhat larger uptake and retention of 3H-NA in the nerve part above the ligation. Protriptyline, a blocker of the “membrane pump”, was approximately 3 times less effective in 12 hr-ligated nerves than in unligated nerves, indicating a reduced efficiency of the “membrane pump” in the distended axons above a ligation.
Peptic inhibition by macroanions
Authors: Anderson W , Baillie A J , Harthill J E
Published: April 2011

Heparin, dextran sulphate, dextran phosphate, chondroitin sulphate and degraded Λ-carrageenan inhibit peptic activity by substrate occlusion or depletion. This holds for various substrates and enzyme preparations, but the amount of inhibition observed varies with method and inhibitor used. The most active inhibitors of the series are disulphated on at least alternate sugar residues and in addition to disulphation high molecular weight confers, in certain conditions, greatest activity. High and low molecular weight macroanions have different inhibition characteristics and it is concluded that activity may depend upon the structure of the substrate-inhibitor complexes formed. Inhibition is not observed when substrate-inhibitor interaction does not occur, as when pepsin or N-acetyl-L-phenylalanine-L-diiodotyrosine (APDT) are used as substrate.
The bactericidal effect of silver ions on Pseudomonas aeruginosa
Authors: Brown M R W , Anderson R A
Published: April 2011

THERE are frequent reports of Pseudomonas aeruginosa infections in hospitals, with contamination of hospital equipment and pharmaceutical preparations (Editorial, 1967). Cason, Jackson & others (1966) report a high incidence of this organism in burn patients and found silver nitrate compresses to be an effective prophylactic measure.

Little information is available on the action of silver ions on Ps. aeruginosa, and the present communication reports the initial stages of such a study. Using cultures whose growth was eventually limited by the magnesium concentration in the culture medium, Brown & Melling (1968) found that Ps. aeruginosa resistance to EDTA was related to the degree of magnesium-limitation. We have examined the effect of magnesium-limitation on sensitivity to silver.
Cell size changes during the growth of Escherichia coli partially inhibited by some antibacterial agents
Authors: Rye R M , Wiseman David
Published: April 2011

The effects of tetracycline, phenol, chloramphenicol and ampicillin on the rates of division and mass increase in growing cultures of Escherichia coli have been examined by comparing the number, carbon content and the size of the cells from partially inhibited cultures with those of control cultures. In cultures treated with low concentrations of tetracycline, phenol or chloramphenicol the increase in cell mass is inhibited more than cell division, thus causing a decrease in the cell size. At higher concentrations of these agents and at all concentrations of ampicillin, cell division is inhibited more than increase in cell mass so causing an increase in cell size.
The uptake of cetyltrimethylammonium bromide by Escherichia coli
Authors: Salt W G , Wiseman David
Published: April 2011

THE uptake of cetyltrimethylammonium bromide (CTAB) by bacteria has previously been examined by Salton (1951) and by McQuillen (1950). Both workers determined its concentration in solutions by titration with sodium cetyl sulphate using pinacyanol bromide as indicator, and reported that uptake was in the form of a typical adsorption isotherm with saturation of the cells at an uptake equivalent to several theoretical close packed monolayers.

This communication reports on studies of the uptake of 14C-labelled CTAB by cells of Escherichia coli and the concurrent release of phosphorus compounds from their metabolic pool.
Binding of crystal violet by nucleic acids of Escherichia coli
Authors: Adams E
Published: April 2011

The absorption isotherms of DNA and RNA from E. coli for crystal violet are sigmoid. Binding of dye was determined i) by difference in its absorbance before and after addition of nucleic acids and ii) by measuring the amount of dye dialysing through a membrane containing dye and nucleic acid. pH change caused no significant change in the degree of binding.
The anomalous chromatographic behaviour of dichlorophen and p-chlorophenol
Authors: Rapson H D C , Scartsiaris Ageliki
Published: April 2011

The variation of Rf value of p-chlorophenol and di-(5-chloro-2-hydroxyphenyl) methane when run alone or together on thin layer chromatograms using toluene and silica gel is attributable to adsorption rather than partition processes. This conclusion is based on a quantitative study of Rf value variation, adsorption and partition behaviour. The adsorption isotherms are used to calculate the Rf values. The latter were of similar magnitude to those obtained directly from the chromatograms.
The polarography of cephalosporin C derivatives
Authors: Jones I F , Page J E , Rhodes C T
Published: April 2011

WE report some preliminary measurements on the polarographic reduction of cephalosporin C, cephalothin [7-(2-thienylacetamido)-cephalosporanic acid] and cephaloridine [7-(2-thienylacetamido)-3-(1-pyridylmethyl)-3-cephem-4-carboxylic acid betaine].

Green, Page & Staniforth (1965) have shown that cephalosporin C derivatives give well-defined infrared and nuclear magnetic resonance spectra that can be used for their qualitative identification. Martin & Shaw (1965) have reviewed the application of methods such as ultraviolet spectrophotometry, paper chromatography and paper electrophoresis for cephaloridine, while Chapman, Page & others (1968) have described infrared and X-ray powder measurements for this compound. The application of mass spectroscopy to the structural elucidation of cephalosporin derivatives has been reported by Richter & Biemann (1965).
The determination of diamorphine by thin-layer chromatography and spectrophotometry
Authors: Davey Elizabeth A , Murray J B , Rogers A R
Published: April 2011

THE assay of diamorphine in Diamorphine Injection B.P. is based on its hydrolysis to morphine followed by a colorimetric determination (Allport & Jones, 1942; Stephens, 1951; Hooper, Shaw & Tims, 1967). Stored solutions of diamorphine may contain O3- and O6-acetyl-morphines as well as diamorphine and morphine (Davey, Murray & Rogers, 1967); all are converted into morphine in the first stage of the British Pharmacopoeial assay of the injection and thus contribute to the final morphine content.

Separation of opium alkaloids and their acetylated derivatives by thin-layer chromatography has already been reported (Mary & Brochmann-Hanssen, 1963; Vignoli, Guillot & others, 1965, 1966a, b) and the application of this technique to diamorphine, the acetylmorphines and morphine is discussed below.
Pharmaceutical applications of vapour-controlled thin-layer chromatography
Authors: De Zeeuw Rokus A
Published: April 2011

In thin-layer chromatography, solvent vapour plays an important role. To obtain full benefit of the influence of vapour in the technique, a new chamber has been developed, providing full vapour control over the entire plate. This allows better separations of chemically related compounds. The properties of the vapour-control chamber are shown in separations of barbiturates and local anaesthetics.
Examination of fennel fruits by gas chromatography without preliminary distillation
Authors: Betts T J
Published: April 2011

IT has been observed that growing fruits of fennel, Foeniculum vulgare Mill., of both the bitter (var. vulgare (Mill.) Thelung) and sweet (var. dulce) forms grown in the same garden develop approximately the same amount of anethole per 100 fruits during their maturation (Betts, 1968). Thirteen dried fennel fruits of various origins have now been examined by gas-liquid chromatography to see how the content and proportion of the essential oil constituents relate to the values previously recorded. Anethole contents differed widely, and a fennel virtually free of anethole was found. Estragole was present instead of anethole, its presence being confirmed by infrared spectroscopy. This fennel has not been reported in commerce before.
Isothermal diffusion measurement on the system water-sodium salicylate-sodium chloride at 25° at one composition
Authors: Deshmukh A , Fleming R
Published: April 2011

The main and cross-term diffusion coefficients for the system water-sodium-salicylate-sodium chloride have been measured at the compositon 0·05 g cc−1, and the results indicate that sodium chloride is effective in producing a flow of sodium salicylate at this concentration. Density, refractive index, partial specific volumes and gravitational data are also reported. The system has been assumed to be 3-component.
Gas-liquid chromatography of heteroyohimbine alkaloids: The effect of methoxy substitution and of configuration
Authors: Beckett A H , Dwuma-Badu D
Published: April 2011

The gas-liquid chromatographic retention times of heteroyohimbine alkaloids on a 1% SE-30 column are in the order pseudo < epiallo < allo < normal. The introduction of one methoxy group into the indole nucleus doubles the retention time while two methoxy groups increase it by a factor of four. Binding of the indole nucleus reinforced by the suitably orientated lone pair electrons of the basic nitrogen to the liquid phase of the column in the important conformers of the various configurations, is used to explain the results.
The crystallization of aspirin from ethanol
Authors: Glasby J , Ridgway K
Published: April 2011

The rate of growth of aspirin crystals has been examined in a circulatory crystallizer in which the crystals are held in suspension as a fluidized bed. The deposition rate was measured, as a function of both the degree of supersaturation and the solution temperature, by observing the rate of weight increase and the change in particle size distribution of the crystals. The dependence of the mass transfer coefficient for the process upon the temperature was of the Arrhenius type, the activation energy being 21·8 kcal/mole. This indicates that the surface reaction step is rate-controlling, diffusional transport to the crystal surface being rapid. The density of aspirin solutions in alcohol has also been measured as a function of temperature and concentration.
An adrenergic neuron blocking action of propranolol in isolated tissues
Authors: Day M D , Owen D A A , Warren P R
Published: April 2011

Propranolol was tested for adrenergic neuron blocking activity in three isolated sympathetically-innervated smooth muscle preparations; the rat vas deferens, rabbit ileum and rabbit ear artery. In each preparation propranolol impaired the responses to sympathetic stimulation without reducing the responses to added noradrenaline. This blocking action of propranolol resembled that of guanethidine in time of onset and persistence of blocking activity but, unlike blocking by guanethidine, was not reversed by (+)-amphetamine. Desipramine and noradrenaline also failed to reverse the blocking action of propranolol. In the rat vas deferens preparation lignocaine had a weaker and more transient sympathetic blocking action than propranolol. It is suggested that the sympathetic blocking action of propranolol may contribute to its antihypertensive effect in man.
The metabolism of 16α-ethylprogesterone by rat liver in vitro
Authors: Stenlake J B , Templeton Richard , Taylor D C
Published: April 2011

The metabolism of 16α-ethylprogesterone by rat liver homogenate at different steroid to tissue ratios has been examined. The products, identified by thin-layer chromatography, gas-liquid chromatography and combined gas-liquid chromatography-mass spectrometry were 16α-ethyl-5α-pregnane-3, 20-dione and 16α-ethyl-3α-hydroxy-5α-pregnan-20-one. The yield of these metabolites was 14 and 48% respectively. The results are discussed in relation to the liver in vitro metabolism of progesterone and 16α-hydroxyprogesterone.
Protein-binding of small molecules: New gel filtration method
Authors: Cooper P F , Wood G C
Published: April 2011

The use of frontal analysis chromatography on Sephadex columns, previously described for protein-protein interactions (Nichol & Winzor, 1964) has been extended to the treatment of protein-small molecule interaction. Chromatograms obtained with bovine serum albumin and three different sulphonamides (sulphanilamide, sulphapyridine and sulphamethoxypyridazine) were found to conform to the theoretical patterns, and the values for the fraction of drug bound were in good agreement with those obtained by equilibrium dialysis.
A modified pressure wheel for the instrumentation of rotary tabletting machines
Authors: Deer J J , Ridgway K , Rosser P H , Shotton E
Published: April 2011

IN any research into tabletting processes, it is necessary to know the force applied at the punch so that the tabletting pressure may be calculated. Much work has been done using single punch machines having strain gauges bonded to the shank of the punch (Higuchi, Nelson & Busse, 1954; Shotton & Ganderton, 1960). High-speed rotary machines require additional sophistication to enable useful results to be obtained, and there are two methods known. The first is that used by Shotton, Deer & Ganderton (1963). The resistance of strain gauges near the punch tips was used to control the frequency of an oscillator, and the signal was transmitted from the rotary part of the machine to a stationary aerial by radio emission. Thus the difficulty of providing a slip ring connection to the strain gauges was circumvented. However, because the radio transmitter took up space normally occupied by punches, it was difficult to obtain readings from more than one pair of punches, and impossible to obtain readings from all. In the second method (Knoechel, Sperry & others, 1967), strain gauges were placed on the compression screws interposed between the arm holding the movable axis of the pressure wheel and the spring used to adjust the compression force applied. Deflection, measured by the strain gauges, was proportional to the force applied to the punch. Since the gauges were stationary, their output could easily be displayed on a cathode ray oscilloscope, and the pressure to each punch recorded as its head passed under the pressure wheel.
The use of diffusion theory for the assessment of mixing in a rotary coating pan
Authors: Ridgway K , Segovia E
Published: April 2011

The effectiveness of a coating pan in treating all the contained tablets identically depends upon its being a good mixing device; the mechanics of particle motion within such a pan are therefore of interest. One measure of the mixing rate in rotary drum mixers is the coefficient of self diffusion, a parameter difficult to measure in a coating pan. Three methods of measuring such a coefficient are reported and compared: linear sampling, total compartmenting of the bed, and high speed cinéphotography. The third method is the best, and a technique is described for treating the pictorial data to obtain quantitative results.
The anti-acetylcholinesterase activities of the alkaloids of Physostigma venenosum seeds
Authors: Robinson B , Robinson J B
Published: April 2011

Anti-acetylcholinesterase activities of physostigmine, physovenine, Na-norphysostigmine, geneserine and eseramine have been investigated in vitro using erythrocyte acetylcholinesterase. The former three bases show comparable activities whereas geneserine and eseramine are inactive under the same experimental conditions. The biologically active form of these bases is discussed in light of these enzyme inhibitory studies.
The dissolution of paracetamol tablets and the in vitro transfer of paracetamol with and without sorbitol
Authors: Walters V
Published: April 2011

MANY adjuvants such as sorbitol, glucosamine hydrochloride and sodium hexametaphosphate, have been added to oral dosage forms to improve the absorption of drugs, but Wagner (1961) emphasizes that the attribution of beneficial results to them is not always unequivocal. With sorbitol in paracetamol tablets, it has been suggested that the improved absorption is due to the sorbitol acting on the metabolism of paracetamol and as a dispersing agent (Gwilt, Robertson & others, 1963). The combination of paracetamol and sorbitol provides a readily assayable system with which to examine the role of the adjuvant.

I have examined the effect of sorbitol on the aqueous solubility and partitioning of paracetamol and have studied the dissolution rate of paracetamol from commercial tablets containing paracetamol with or without sorbitol with the aim of evaluating the effect of the adjuvant on the availability of the drug.
The influence of alkyl substitution in acids on their performance in the buccal absorption test
Authors: Beckett A H , Moffat A C
Published: April 2011

A method to determine the passage of acids into the buccal membrane of man is presented. The absorption is shown to be the passive entry into a lipid phase. There is an increase in absorption of the acids due to alterations in partition characteristics with increasing chain length of n-fatty acids from butyric to dodecanoic. Methyl substitution of benzoic acid increases the absorption with mono- and di-substituents, but decreases the absorption with the tri- and tetra-substituents by lowering the pKa. Predictions of the relative absorption and excretion in man of these acids is included.
Examination of the hallucinogen 2,5-dimethoxy-4-methylamphetamine
Authors: Phillips G F , Mesley R J
Published: April 2011

Physical characteristics are reported for a tablet form of a new hallucinogenic drug previously circulating in the USA under the name “STP”. High resolution mass, nmr, ultraviolet and infrared spectrometric evidence, which identify the extracted base as 2,5-dimethoxy-4-methylamphetamine, and its chromatographic behaviour, are compared with the experimental compound “DOM”. Polymorphic modifications exhibiting distinct solid phase infrared spectra have been studied by X-ray diffraction and by differential calorimetry. Animal behavioural tests indicate that the psychotomimetic activity of the base is comparable with mescaline but up to 50 times more potent.
Infrared identification of lysergide (LSD)
Authors: Mesley R J , EVANS W H
Published: April 2011

Infrared spectra of LSD and its tartrate salts, and factors affecting their reproducibility, have been investigated. Spectra corresponding to amorphous and crystalline forms of LSD base, the neutral tartrate and two forms of the hydrogen tartrate were obtained. The neutral tartrate was found to undergo conversion to the hydrogen tartrate on long standing. Comparison with spectra of related compounds shows that all the LSD spectra are distinctive and can be used for identification purposes, but the use of potassium bromide discs was found to cause spectral changes in the salts.
The flow of granular solids through circular orifices
Authors: Harwood C F , Pilpel N
Published: April 2011

It has been shown that the use of the bulk density term in place of the particle density, in the equation of flow for granular solids passing through a circular orifice, very largely eliminates differences due to the shape, rugosity, density, porosity and friction of the particles.

The equation

has been tested on seven different materials and has been found to predict the flow of single and binary systems with an overall accuracy of ±5% and ±10% respectively.
The effect of dimensions on the compaction properties of sodium chloride
Authors: Rees J E , Shotton E
Published: April 2011

Using a tablet press instrumented with strain gauges, anhydrous particulate sodium chloride was compressed to form compacts of different lengths in three dies of different diameters. For the limited range of dimensions applicable to most pharmaceutical tablets, there was a common linear relation between the applied compaction pressure and the force lost to the die wall per unit area of apparent die wall contact, during compression. Ejection forces were correlated using a similar expression. The mechanical strength of compacts was determined by diametrical compression. A relation was proposed to express the strength (Fe), of the compacts of different sizes in terms of the diametrical cross-sectional area at zero porosity (D.Lo), the relative volume (Vr) and the mean compaction pressure (Pm):

, where k and c are constants.
The effect of sodium salicylate on the binding of l-tryptophan to serum proteins
Authors: McArthur J N , Dawkins P D
Published: April 2011

In human serum, l-tryptophan is the only amino-acid bound to protein. Salicylate causes a release of tryptophan from its binding sites on human serum proteins and bovine albumin. Some implications of this finding are discussed.
The inhibition of human platelet 5-hydroxytryptamine uptake by tricyclic antidepressive drugs. The relation between structure and potency
Authors: TODRICK A , Tait A C
Published: April 2011

Thirty-five compounds related to the antidepressive drug imipramine in chemical structure have been examined for their capacity to inhibit the uptake of 5-hydroxytryptamine by human platelets in vitro. Substitution by small-sized electropositive groups in positions 2 or 3 of a benzene ring gave compounds more active than the prototype, 3-chloroimipramine being five times as potent on this test. Alteration of the characteristic seven-membered ring of the antidepressive drugs reduced the activity while substitution in the basic side-chain destroyed it. The tertiary amines were more potent inhibitors than their demethylated derivatives. In this and other ways the active structure for the inhibition of 5-ht uptake by human blood platelets differs from that for the inhibition of noradrenaline uptake by the rat heart.
On the local anaesthetic effect of barbiturates
Authors: Krupp P , Bianchi C P , Suarez-Kurtz G
Published: April 2011

Controversy exists about whether the free acid (non-ionized) or the anionic (ionized) form of barbiturates abolish the excitation of nerves. The experiments made showed that sodium pentobarbitone and sodium phenobarbitone are more effective at pH 6·8 than 8·8 in blocking the action potential in the desheathed frog nerve. The experimental procedure employed excludes the possibility that this difference in activity is due only to a more effective rate of penetration of the non-ionized form across the nerve membrane. In the same preparation these barbiturates at both pH 6·8 and 8·8 did not interfere with the uptake and release of radiocalcium. These data suggest that barbiturates block the action potential by increasing the surface pressure of the lipid layer of the excitable membrane and do not interfere with the calcium binding to sites which govern the increased membrane conductance during excitation.
The effect of anti-Parkinsonian drugs on oxotremorine-induced analgesia in mice
Authors: Leslie G B
Published: April 2011

The antagonism of oxotremorine-induced analgesia in mice can be used to obtain a quantitative and objective assessment of the central anticholinergic activity of potential anti-Parkinsonian drugs.
Dopa-induced locomotor stimulation after inhibition of extracerebral decarboxylase
Authors: Bartholini G , Blum J E , Pletscher A
Published: April 2011

In rats, a combination of small doses of the dopa decarboxylase inhibitor Ro 4–4602 [N-(DL-seryl)-N’-(2,3,4-trihydroxybenzyl)hydrazine] with dopa causes a marked enhancement of the spontaneous locomotor activity which is not seen with dopa alone. If high instead of low doses of Ro 4–4602 are used, locomotor stimulation does not occur. Low doses of Ro 4–4602, owing to selective inhibition of extracerebral decarboxylase, enhance the dopa-induced rise of dopa and catecholamines in the brain, whereas high doses of Ro 4–4602, which also inhibit the cerebral dopa decarboxylase, increase only the level of dopa but not that of the catecholamines. It is concluded that the locomotor activation after small doses of Ro 4–4602 in combination with dopa is due to cerebral accumulation of catecholamines which consist mainly of dopamine.
The influence of ATP in brain extracts on the estimation of acetylcholine assayed on the frog rectus abdominis muscle
Authors: Stockley I H
Published: April 2011

Comparative studies of the sensitizing properties of creatine phosphate, ATP and a trichloroacetic acid brain extract on the acetylcholine-induced contractures of the frog rectus muscle indicate that alkaline boiling increases the sensitizations due to these substances threefold. This increase is reflected in a 25% reduction in the values for acetylcholine in brain extracts when assayed on the rectus muscle using Feldberg’s method. Since tissue extracts made with acid-alcohol, formic acid-acetone, eserine-saline and sucrose-saline also contain sensitizing substances, the acetylcholine values obtained by this assay method may be in error.
The bronchodilator action of analeptics in the guinea-pig
Authors: Lessin A W , Kramer R L
Published: April 2011

Picrotoxin, leptazol, nikethamide and bemegride were found to antagonize the bronchoconstrictor effects of acetyl-β-methylcholine in the guinea-pig anaesthetized with urethane. The analeptics were also active in pithed animals but not in animals that had been adrenalectomized or pretreated with propranolol. Catecholamine release from the adrenals can account for the effects observed.
Application of differential scanning calorimetry to the study of sulphathiazole crystal forms
Authors: Moustafa M A , Carless J E
Published: April 2011

Methods of preparation and characterization of two crystal forms of sulphathiazole using differential scanning calorimetry and infrared spectroscopy are described. Heats of transition and fusion calculated from thermal analysis are 1778±68 Cal mol−1 and 6615 ± 235 Cal mol−1 respectively. The transition temperature depends on the rate of heating and the sample source. Interconversion of the crystal forms under different conditions such as heating and suspension in water is described. An assay procedure based on the area of the thermal transition peak of Form I was devised and results of analysis of synthetic mixtures of Forms I and II are given.
Central muscle relaxant properties of 2,6-dimethylphenethylurea and related compounds
Authors: Green A L , Willey G L
Published: April 2011

Twenty-eight phenylalkylureas with alkyl, hydroxy, methoxy or chloro-substituents in the aryl ring have been synthesized and tested for central depressant and muscle relaxant properties. In this series, the dimethylphenethylureas with at least one ortho-methyl group show unexpectedly selective muscle relaxant activity. 2,6-Dimethylphenethylurea inhibits polysynaptic reflexes more readily than monosynaptic ones, but also depresses muscle contractions by an action independent of its effect on interneuronal transmission. It is a weak anticonvulsant, suppresses rage episodes in “fighting” mice, and has no selective blocking action on conditioned responses. It thus has a pharmacological profile resembling those of mephenesin and meprobamate, but distinct from either, and differing still more from those of phenobarbitone, chlordiazepoxide or chlorpromazine. However, tolerance to its action develops readily.
The use of the in vivo trachea preparation of the guinea-pig to assess drug action on lung
Authors: Lynn James G W
Published: April 2011

A method for recording the effects of drugs on an isolated in vivo segment of trachea and on lung pressure of a deeply anaesthetized animal is described. Acetylcholine, angiotensin, histamine, 5-hydroxytryptamine, prostaglandin (PG) F2α and slow-reacting substance of anaphylaxis, but not bradykinin, caused an increase in tracheal segment pressure and an increase in lung pressure. Bradykinin caused an increase in lung pressure but a fall in tracheal segment pressure. It was concluded that bradykinin acts mainly on the smaller airways and PGF2α mainly on the larger airways. The tracheal segment responded to adrenaline, aminophylline, ephedrine, isoprenaline, papaverine, PGE1 and PGE2. Propranolol reduced or abolished responses to all these bronchodilators except PGE1 and PGE2.
Effect of nialamide and methyldopa on the analgesic action of morphine in rats and mice
Authors: Contreras E , Tamayo L , Quijada L
Published: April 2011

Methyldopa and nialamide enhance the analgesic action of morphine when administered separately in the rat. However, the association of both drugs in the same animal diminishes the effect of the analgesic. Results observed in mice differ from those found in rats, whereas methyldopa induces a slight increase in morphine analgesic effect, nialamide is ineffective. The administration of both drugs in combination increases morphine effect in a way similar to that obtained when methyldopa and morphine are administered together.
Structure-activity relations in analgesics based on 4-anilinopiperidine
Authors: Casy A F , Hassan M M A , Simmonds ALMA B , Staniforth D
Published: April 2011

The synthesis of some 1-alkyl and l-aralkyl-4-(N-phenylpropion-amido)piperidines and related derivatives is described and the hot-plate activities in mice of these compounds reported. Activity variations among 1-methyl, 1-benzyl, and 1-phenethyl derivatives resemble those of corresponding open-chain anilide rather than 4-phenyl-piperidine analgesics. Infrared and nmr data show the two nitrogen atoms of the 4-anilinopiperidine derivatives to be further apart than those of open-chain anilides in their respective preferred conformations; these results, together with the extreme potency difference between the N-phenethyl derivatives diampromide and fentanyl, show that the two classes are best regarded as mutually distinct types of analgesic.
The hardness and elastic modulus of some crystalline pharmaceutical materials
Authors: Ridgway K , Shotton E , Glasby J
Published: April 2011

The surface microhardnesses of single crystals of the following materials have been measured: aspirin, hexamine, sodium chloride, potassium chloride, urea, salicylamide and sucrose. A Leitz microhardness tester was used, with indentor loads of 25 g or less, in order to give indentations of less than 50 μm diagonal length and enable measurements to be made on single crystals. The compressive elastic modulus of some of the crystals was also determined using a “Techne” microtensile tester modified to work in compression. When the materials are listed in order of magnitude of Young’s modulus, this order is the same as when they are listed in order of magnitude for surface hardness.
The effect of crystal hardness on radial pressure at the wall of a tabletting die
Authors: Ridgway K , Glasby J , Rosser P H
Published: April 2011

The force transmitted to the die wall during the tabletting of seven crystalline pharmaceutical materials has been measured using a photoelastic technique. The Vickers hardness of these materials has also been measured. The compounds examined were aspirin, urea, hexamine, salicylamide, potassium chloride, sodium chloride and sucrose. The pressure on the die wall increases as the hardness value decreases. The Vickers hardness of the resultant tablets was also measured; aspirin and sodium chloride both showed the occurrence of work hardening in that the tablets had a greater hardness value than the parent crystalline substance.
The effect of particle shape on powder properties
Authors: Ridgway K , Rupp R
Published: April 2011

Sand in the size ranges 18–20 mesh, 30–36 mesh and 44–60 mesh has been separated by means of a vibratory shape-sorting table into fractions of different shape. The ratios of the surface area of the particles to their volumes-the shape coefficients-ranged from 8 to 15. For each fraction the following properties were measured: angle of repose, bulk density and rate of flow through an orifice. In all cases, with increasing departure from the spherical, the angle of repose increased, whilst the bulk density and flowability decreased. Improved methods are reported for the measurement of bulk density, angle of repose and specific surface area in the range 30–130 cm2/g.
Crystal growth studies involving phase transitions in aqueous drug suspensions
Authors: Pearson J T , Varney G
Published: April 2011

The growth of oxyclozanide crystals in quiescent suspensions has been monitored using the Coulter Counter. Increase in particle size is the result of an isothermal, solvent-mediated phase transition between two unsolvated polymorphs, one having a lower solubility than the other. Effects due to Ostwald ripening and temperature cycling are absent. Theophylline, which shows crystal growth in suspension by hydration, has been studied by photomicrography. Preliminary results indicate that the initial rate of growth in such systems may be qualitatively described in terms of steady-state diffusion theory.
The morphology and anatomy of the flowers of Mitragyna inermis (Willd.) O. Kuntze
Authors: Shellard E J , Wade A
Published: April 2011

The morphology and anatomy of the flowers of Mitragyna inermis have been described and a comparison made with the flowers of Mitragyna ciliata and Mitragyna stipulosa.
Excretion of cocaine and its metabolites in man
Authors: Fish F , Wilson W D C
Published: April 2011

Little information exists on the metabolism, distribution and excretion of cocaine in persons dependent upon it. We now present results showing the proportions of cocaine excreted unchanged and as its metabolite benzoylecgonine.
Correlation of partition coefficients in n-heptane-aqueous systems with buccal absorption data for a series of amines and acids
Authors: Beckett A H , Moffat A C
Published: April 2011

Partition coefficients in n-heptane-0·1n sodium hydroxide or 0·1n hydrochloric acid have been determined for a series of amines and acids; linear relations between chain-lengths and the logs of their partition coefficients were found. The plot of alkyl chain-length against buccal absorption of some amphetamines and fenfluramines, when they were 1% unionized, was linear. There was also a linear relation between the logs of the partition coefficients and buccal absorption of the amines and acids when these were 1 and 10% unionized. Those amines and acids having similar partition coefficients, when equally unionized, were absorbed to the same extent in the buccal test over the pH range 4 to 9. During the test the pH at the surface of the buccal membrane was shown to be the same as that of the solution in the mouth. n-Heptane is considered to be equivalent in solvent properties to the buccal lipid membrane for the compounds used in the present test.
Urinary excretion of the drug and its main metabolite in man, after the administration of (±)-, (+)- and (-)-ethylamphetamine
Authors: Beckett A H , Brookes L G , Shenoy E V B
Published: April 2011

The urinary excretion of ethylamphetamine and its metabolite amphetamine was studied in man after oral administration of (±)-, (+)-, and (-)-ethylamphetamine hydrochloride. The rates of excretion of these amines are dependant on the pH of the urine. At acid values, the (+)-isomer is metabolized faster and to a greater extent than the (-)-isomer, which is excreted mostly unchanged. The effect of alkyl chain length on stereoselective metabolism of N-alkylamphetamines is discussed.