bluuebunny/crossref_metadata_2025 huggingface dataset:
Competitive antagonism of isoprenaline-induced cardiac necroses by β-adrenoreceptor blocking agents
Authors: Dorigotti L , Gaetani M , Glässer A H , Turolla E
Published: April 2011

Histological methods show that low doses of (±)-isoprenaline may produce cardiac necroses in the rat. The percentage of animals with focal necroses was related to the dose within the range 0·005 to 0·5 mg/kg administered subcutaneously. Therefore the heart-damaging effect of isoprenaline as well as the antagonistic effect of β-adrenoreceptor blocking agents could be evaluated quantitatively. Pre-treatment of animals with dichloroisoprenaline, pronethalol and propranolol produced a parallel displacement to the right of the dose-response line for isoprenaline. However, when lesions were already in progress, these agents were without protecting effect.
Simulation of the apparent effects of mebanazine on growth hormone by pair-feeding of control animals
Authors: Barrett A M
Published: April 2011

The degree and duration of insulin hypoglycaemia was potentiated by chronic oral medication with mebanazine in rats. Hypophysectomy alone increased sensitivity to insulin but did not abolish the potentiating effect of mebanazine. Chronic mebanazine treatment (15 mg/kg/day) for 6 weeks markedly reduced weight gain, food and water consumption and pituitary growth hormone content, but the results were not significantly different from those in unmedicated pair-fed controls. Similarly, immature rats treated with mebanazine had a significant reduction in the width of the tibial epiphysial cartilage but this was not different from that in pair-fed animals. After 18 h of fasting, acute administration of mebanazine had little effect on food consumption in the 2 h period following dosing but a significant effect over 24 h. In fed rats mebanazine in a single oral dose significantly reduced eating in the following 6 h. Treatment with mebanazine at 2·5 mg/kg for 15 days significantly reduced food intake but did not potentiate insulin hypoglycaemia. From the results it would appear that previous suggestions that mebanazine specifically interferes with growth hormone release are incorrect and the findings emphasize the importance of measuring food intake in experiments of long duration.
The control of oil-in-water emulsion consistency using mixed emulsifiers
Authors: Barry B W
Published: April 2011

Mixtures of emulsifiers of the surfactant-fatty alcohol type are widely used to stabilize oil-in-water emulsions and to alter their consistency from fluid to semi-solid. A mechanism, involving the formation of a viscoelastic network in the continuous phase, is proposed to explain this self-bodying action. Evidence has been adduced from published data on a variety of systems. Support for this concept is also provided by the results obtained from a concentric cylinder study of the rheology of liquid paraffin in water emulsions containing a fixed concentration of cetostearyl alcohol and varying amounts of polyoxyethylene sorbitan monooleate, cetomacrogol 1000, sodium dodecyl sulphate or cetrimide.
Interaction between phenylpropanolamine and monoamine oxidase inhibitors
Authors: D’Mello A
Published: April 2011

The role of monoamine oxidase in the potentiation of the pressor effect of phenylpropanolamine (norephedrine) by monoamine oxidase inhibitors has been investigated. In vitro, phenylpropanolamine was not a substrate of monoamine oxidase from guinea-pig liver. In spinal cats the pressor effects of both phenylpropanolamine and tyramine were potentiated by a monoamine oxidase inhibitor, nialamide, and by the microsomal enzyme inhibitor SKF 525-A, which is not a monoamine oxidase inhibitor. These results suggest that the enhanced pressor effect of phenylpropanolamine in the presence of monoamine oxidase inhibitors is caused by inhibition of other enzymes.
Adrenergic neuron blocking properties of (±)-propranolol and (+)-propranolol
Authors: Barrett A M , Nunn Barbara
Published: April 2011

The action of (±)-propranolol and (+)-propranolol on the electrical stimulation of adrenergic nerves to smooth muscle has been studied in the isolated ear artery from rabbits and the isolated vas deferens preparation from rats. Both drugs exhibited an adrenergic neuron blocking action at a pre-junctional site at concentrations ranging from 4·6 to 14 μg/ml. At lower concentrations the effects were variable and more often potentiation of the responses was observed. The responses to added noradrenaline were uniformly potentiated. The effect was related to local anaesthetic activity and not considered to be a specific adrenergic neuron blocking effect as occurs with guanethidine or bretylium.
The interaction of ethanol and amphetamine metabolism
Authors: Creaven P J , Barbee Theresa , Roach Mary K
Published: April 2011

Ethanol, 1, 3, and 5 g/kg, depresses the hydroxylation of amphetamine by the rat in vivo. At 5 g/kg, ethanol does not affect the hydroxylation of acetanilide or biphenyl in vivo. Amphetamine hydroxylation is unaffected by phenobarbitone or benzo[a]pyrene pretreatment but is depressed by pretreatment with 2-diethylaminoethyl-2, 2-diphenyl-valerate (SKF 525-A), 2, 4-dichloro-6-phenylphenoxyethylamine (DPEA), and 2, 4-dichloro-6-phenylphenoxy-NN-diethylethylamine (Lilly 18947).
The biliary metabolism of butylated hydroxytoluene (3, 5-di-t-butyl-4-hydroxy-toluene) and its derivatives in the rat
Authors: Holder G M , Ryan A J , Watson T R , Wiebe L I
Published: April 2011

The biliary metabolism of 3, 5-di-t-butyl-4-hydroxybenzyl alcohol (BHT-CH2OH), 3, 5-di-t-butyl-4-hydroxybenzaldehyde (BHT-CHO) and 3, 5-di-t-butyl-4-hydroxybenzoic acid (BHT-COOH) after parenteral administration has been examined in the rat and compared to that of 3, 5-di-t-butyl-4-hydroxytoluene. Quantitative excretion and chemical examination of bile showed that in the enterohepatic circulation BHT-COOH or its ester glucuronide is the recirculating compound from the four compounds studied. Biliary excretion data are also presented for 1, 2-bis(3, 5-di-t-butyl-4-hydroxyphenyl)ethane.
Microcrystalloptic tests for lysergic acid diethylamide and other hallucinogens
Authors: Genest K , Lowry Lorna J
Published: April 2011

Microcrystallopic tests for LSD, NN-diethyltryptamine, NN-dimethyltryptamine, bufotenine, psilocin, psilocybin and STP are described. The tests are recommended in conjunction with other analytical techniques if applied for the forensic identification of hallucingens.
A note on the identification of sulphonamides by thin-layer chromatography
Authors: clarke E G C , Humphreys D J
Published: April 2011

A method is described for the identification of 25 sulphonamides by thin layer chromatography. Four systems are used, the solvents being (I) chloroform-methanol (4:1), (II) chloroform-carbon tetrachloride-methanol (7:2:1), (III) ethyl acetate-methanol (9:1), (IV) acetone-methanol (4:1), the plates being coated with silica gel G mixed with (I) sodium hydroxide, (II) potassium hydrogen sulphate, (III) water, (IV) sodium hydroxide. The location reagents are (a) copper sulphate, (b) p-dimethylamino-benzaldehyde, (c) N(1-napthyl) ethylenediamine di-HCl, and (d) fluorescein.
Application of the ΔA method to the determination of morphine
Authors: Wahbi A M , Farghaly A M
Published: April 2011

Tablets, suppositories and ear-drops have been assayed using the ΔA method to eliminate interferences. The absorbance at 298 nm is measured for solutions in acid and alkaline media, the difference (Δ A) being taken as a measure of morphine content. The same method has been applied to suppositories after extraction of the drug from the base. Ear-drops containing phenol in addition to morphine were assayed by measuring ΔA at 288 and 298 nm and evaluating the morphine concentration from a pair of simultaneous equations.
Structure-activity relations for anticholinergic dioxolans
Authors: Brimblecombe R W , Inch T D
Published: April 2011

4-Dimethylaminomethyl 1, 3-dioxolan derivatives have been examined for anticholinergic potency. Quaternary derivatives in which C-2 was substituted with two bulky substituents were found to have anticholinergic potencies similar to those of atropine in the peripheral nervous system. A comparison of the enantiomeric cis and trans 2-cyclohexyl-2-phenyl-4-dimethylaminomethyl-1, 3-dioxolan methiodides showed that the observed configurational selectivity depended mainly on the configuration at C-2 and not on the geometrical relation between C-2 and C-4.
The effects of salicylate on the concentrations of amino-acids in mouse tissues
Authors: Dawkins P D , Smith M J H
Published: April 2011

The concentrations of amino-acids in chopped preparations of mouse liver incubated with 0 to 20 mM salicylate were measured. The changes, observed with salicylate concentrations of 10 mM and above, were increased concentrations of aspartate, glutamine, tyrosine and ornithine and decreased concentrations of glutamate and γ-aminobutyrate. The effects of the intraperitoneal injection of salicylate, in doses ranging from 75 to 600 mg/kg body weight, on the amino-acid concentrations in mouse blood, kidney, liver and brain were studied. With a dose of 600 mg/kg, the amino-acid concentrations were decreased in the blood (except glutamate and aspartate which increased) and in the kidney, were increased in the liver (except glutamine, glutamate, glycine and alanine which decreased) and were unchanged in the brain (except alanine, valine and leucine which decreased and γ-aminobutyrate which increased). These changes may result from a combination of an inhibitory effect of salicylate on the renal tubular transport of the amino-acids and intracellular actions of the drug on aminotransferase and other enzyme activities.
Phosphocholine 2, 6-xylyl ether bromide: proton-phosphorus coupling constants and preliminary pharmacological assessment
Authors: Clark E R , Hughes I E
Published: April 2011

Phosphocholine 2, 6-xylyl ether bromide [PPP-trimethyl-2-(2, 6-xylyloxy)ethylphosphonium bromide], has been synthesized by reacting 2-(2, 6-xylyloxy)ethyl bromide with a solution of trimethyl-phosphine in phenol, but ethylenebis(trimethylphosphonium bromide), 1, 2-di(2, 6-xylyloxy)ethane and 2, 6-xylenol were the only reaction products identified when ether was used as solvent. The 2JPH and 3JPH coupling constants for these phosphonium salts have been determined. Although the phosphocholine xylyl ether blocks the Finkleman preparation in concentrations of 2–3 × 10−5 g/ml, this blockade does not have all the characteristics of the adrenergic neuron blockade produced by xylocholine.
The mode of action of insulin potentiation by mebanazine
Authors: Barrett A M
Published: April 2011

Chronic oral treatment of rats with mebanazine potentiated the hypoglycaemic response to insulin both in intensity and duration. A similar potentiation of intensity but not of duration was observed in pair-fed animals. In consequence, mebanazine-treated rats subjected to a 21 h fast before insulin died in hypoglycaemic coma whereas control and pair-fed animals did not. Intravenous glucose brought about a rapid return to consciousness in moribund mebanazine-treated rats in insulin coma but hyperglycaemic catecholamines did not. The observed hypoglycaemic unresponsiveness was not solely due to depletion of liver glycogen since both control and treated rats had undetectable levels of glycogen after fasting, yet only the treated animals died. Tissue levels of noradrenaline were raised by mebanazine treatment in brain, heart and liver but these enlarged stores were readily depleted by reserpine. A similar potentiation of hypoglycaemia was observed following chronic treatment of intact rats with tranylcypromine and of adreno-demedullated rats with guanethidine and bethanidine. No potentiation was observed with reserpine or α-methyldopa in either type of animal. Blood glucose was significantly raised by adrenaline and α-methylnoradrenaline, but not by octopamine. The observations support the hypothesis that hypoglycaemic unresponsiveness following chronic inhibition of monoamine oxidase is due to a replacement of noradrenaline in adrenergic neurons by octopamine. This substance is an ineffective hyperglycaemic agent and its physiological release in response to hypoglycaemia does not bring about a return to normoglycaemia.
Inhibition of enzymes by alkylsalicylic acids
Authors: McCoubrey A , Smith M H , Lane A C
Published: April 2011

5-n-Alkylsalicylates inhibited a variety of enzymes that transform acidic substances, viz. glucose-6-phosphate dehydrogenase, glyoxalase, xanthine oxidase, carbonic anhydrase and D-amino-acid oxidase. Inhibitory potency rose to a peak at the n-nonyl derivative. None of the tests were of value, either singly or in combination, as screening processes for anti-inflammatory activity. The comparable results with a trinitrobenzaldehyde reagent suggest that the various inhibitions arise by non-specific association of the drugs with arginine and lysine residues in proteins.
The effect of granule properties on the pore structure of tablets of sucrose and lactose
Authors: Ganderton D , Selkirk A B
Published: April 2011

Air permeability and liquid penetration of tablets of sucrose and lactose have been measured. The tablets had been compressed over a wide pressure range from granules which varied in bulk density, size and strength. The degree to which inter- and intra-granular pore structure within the tablet was sustained varied with these properties; low pressure, high density, high strength and large size promoting a more open but less uniform structure. Such structures allowed rapid penetration of liquid through a coarse pore network which isolated a large fraction of the total pore space. Thus tablets of high permeability gave low final degrees of saturation whereas less permeable tablets became fully saturated.
The effect of sodium salicylate on the binding of long-chain fatty acids to plasma proteins
Authors: Dawkins P D , McArthur J N , Smith M J H
Published: April 2011

Salicylate causes a release of palmitic, stearic, oleic and linolenic acids from their binding sites on human plasma proteins and bovine albumin. The implications of this finding with respect to other effects of salicylate on fatty acid metabolism are discussed.
Medicament release from fatty suppository bases
Authors: Baichwal Malati R , Lohit T V
Published: April 2011

The consistency in terms of viscosity index and the rheology of mixtures of cacao butter with different fats was examined with a Stormer viscometer. Most bases showed shear rate thickening at low stresses and marked fall in consistency between 35°–40°. The drug release from them was related inversely to the consistency of the bases.
Pharmacological actions of phosphocholine 2,6-xylyl ether bromide (phospho-TM10; PTM10)
Authors: Hughes I E
Published: April 2011

PPP-Trimethyl-2-(2,6-xylyloxy)ethylphosphonium bromide (PTM10; phospho-TM10), the phosphorus analogue of xylocholine (TM10), has been found to possess local anaesthetic, α-adrenoceptor and ganglion blocking properties. It also shows a blocking action at the neuromuscular junction but has no detectable adrenergic neuron blocking properties. The relation of these results to the ‘cholinergic link” hypothesis of Burn and Rand is discussed.
The influence of angiotensin on the uptake of noradrenaline by the isolated heart of the rabbit
Authors: Schümann H J , Starke K , Werner U , Hellerforth R
Published: April 2011

The influence of angiotensin on the removal of noradrenaline (10 ng/ml) from the perfusion medium and on the net-uptake of noradrenaline (5 and 20 μg/ml) was examined in the rabbit isolated heart. Concentrations of angiotensin, known to augment the output of noradrenaline from rabbit heart during sympathetic nerve stimulation, did not inhibit the removal of infused noradrenaline from the perfusion fluid. Only very high concentrations of angiotensin (13 μg/ml) significantly diminished the loss of noradrenaline. The positive inotropic effect of noradrenaline was not potentiated by angiotensin. On the other hand, cocaine, in doses which enhance the output of noradrenaline during sympathetic stimulation greatly reduced the loss of noradrenaline from the perfusion fluid. Neither angiotensin (130 ng/ml) nor metanephrine (5 and 20 μg/ml) significantly influenced the net-uptake of noradrenaline from high concentrations. The observations made support the assumption that an increase of transmitter liberation rather than inhibition of transmitter inactivation is responsible for the increase caused by angiotensin in the output of noradrenaline during stimulation of sympathetic nerves.
The compression properties of lactose
Authors: Alpar Oya , Hersey J A , Shotton E
Published: April 2011

The tabletting characteristics of crystalline and spray dried lactose under direct compression have been examined together with the effect of particle size, shape and storage of the powders. The results indicated that the particle size had little effect, although there was a general tendency for the compact strength to increase as the particle size decreased. On the other hand, the particle shape and storage of the powder influenced the strength of the tablets and the force lost to the die wall. The 22 μm and 35 μm fractions of spray dried lactose—especially the latter—were almost entirely very regular spherical particles which resulted in the strongest tablets, whereas fractions below or above contained many more angular particles resulting in weaker tablets. Storage of the small particle size fraction of the crystalline material appeared to induce aggregation, and on compaction, a harder tablet was formed, accompanied by a decrease in the force lost to the die wall.
The alkaloidal pattern in the leaves, stem-bark and root-bark of Mitragyna species from Ghana
Authors: Shellard E J , Sarpong K
Published: April 2011

The leaves, stem-bark and root-bark of Mitragyna ciliata, M. inermis and M. stipulosa have been examined quantitatively and qualitatively for alkaloids. In addition, the plant parts of M. stipulosa collected at 12 regular monthly intervals have been similarly examined. The presence of mitraphylline in the leaves of this plant and the absence of indole alkaloids was confirmed. The predominant leaf alkaloids are oxindoles of the A series, those of the stem- and root-bark, oxindoles of the B series. Whereas the general alkaloidal pattern of M. ciliata appears similar to that of M. inermis rather than M. stipulosa, a more detailed study suggests that M. ciliata and M. inermis have a distinctly different metabolic pattern in relation to the C(9)-OMe alkaloids.
Physico-chemical studies of analgesics. The protein-binding of some p-substituted acetanilides
Authors: Dearden J C , Tomlinson Eric
Published: April 2011

The binding of fifteen p-substituted acetanilides to bovine serum albumin is examined at pH 7·2. An excellent correlation is obtained between the binding enthalpy and Hammett’s substituent constant, s̀. This is interpreted to mean that the binding is non-specific in nature. A very good correlation is also obtained between the entropy of binding and s̀, which suggests that the extent of hydration of unbound drug is a function of the charge separation within the drug molecule. Of the compounds examined, those that have been used clinically as analgesics possess the best thermodynamic properties, being neither so fully bound as to give low free drug concentrations in the bloodstream, nor so little bound that there is no sustained action.
The effect of rate of loading on the strength of tablets
Authors: Rees J E , Hersey J A , Cole E T
Published: April 2011

The breaking strength of tablets containing lactose and microcrystalline cellulose has been determined using an Instron Universal Testing Instrument at loading rates corresponding to cross-head movements of 0·05 to 5·0 cm min−1. For tablets of 2 to 30 kg, nominal strength, an increase in the loading rate produced a significant increase in the breaking strength, although the absolute increase in the mean strength value was only 2 kg for the strongest tablets. The standard deviation of replicate values was apparently unaffected by loading rate. Results obtained using the motorized Heberlein and Erweka instruments to determine the strength of compressed tablets, indicated that discrepancies in the strength values may be partially attributed to differences in the rates of loading.
An investigation of the pore structure of tablets of sucrose and lactose by mercury porosimetry
Authors: Selkirk Alastair B , Ganderton David
Published: April 2011

The pore structure of tablets has been investigated by mercury porosimetry. Tablets, when prepared from ungranulated powder, showed a narrow pore size distribution, the mode of which decreased from 9 to 1 μm over the pressure range studied. Granulation caused the size distribution of tablet pores to widen. Large robust granules, compressed at low pressures, gave tablets with a bimodal pore size distribution. Decrease in granule size and strength, promoted a more uniform tablet structure and fine, friable, granules, compressed at high pressures, gave tablets with almost the same structure as those prepared from ungranulated powder.
An infrared study of solute-solvent interactions of testosterone propionate
Authors: James K C , Noyce P R
Published: April 2011

Interactions between testosterone propionate and 10 different organic solvents have been investigated by observing the shifts of the stretching frequencies of the ketone and ester carbonyl groups. The shifts are shown to be approximately proportional to the degree of deviation from regular solution behaviour. The solvents are classified into three groups and the possible interactions in each discussed.
Adsorption of non-ionic surfactants at the griseofulvin-solution interface
Authors: Elworthy P H , Guthrie W G
Published: April 2011

The adsorption from solution onto griseofulvin powder of a series of non-ionic detergents of the polyoxyethylene glycol mono alkyl ether type is described. Results are also given for polyethylene glycol 400 and a new detergent, pentaerythritol mono-n-octyl ether, whose synthesis and purification is reported. The effect of temperature on the adsorption is studied and possible explanations of the variation of adsorption with temperature are based on the orientation of the molecules at the interface; this is deduced from measured molecular areas.
The use of a bromide ion selective electrode for the measurement of counter-ion activity in cationic surfactant solutions
Authors: Pearson J T , Humphreys K J
Published: April 2011

A bromide ion selective electrode has been used in conjunction with a saturated calomel reference electrode to measure bromide ion activity in solutions of n-decyl, n-dodecyl, n-tetradecyl and n-hexadecyl 1-trimethylammonium bromides at 30°; the critical micelle concentrations of the surfactants were measured by electrical conductance. Calibration of the electrode pair in potassium bromide solutions produced a linear response over the range 0·5 to 5·0p Bra− with a slope of 59·1 mV for a 10-fold change in activity. Results for the surfactants were treated to give values for the degree of micellar dissociation; literature values for this quantity reveal wide variation depending on the technique used.
On the release of drug from hard gelatin capsules
Authors: Newton J M , Rowley G
Published: April 2011

The effect of particle size and packing on the in vitro release of a water-insoluble hydrophobic drug from hard gelatin capsules has been related to the liquid permeability of powder beds of similar porosities. Drug release and permeability decrease with a decrease in particle size and porosity of the powder bed. A simple moist granulation process transforms a non-permeable powder bed, which allows low drug release, into one with high permeability and high drug release.
The absorption and excretion of carbenoxolone in man
Authors: Downer H D , Galloway R W , Horwich L , Parke D V
Published: April 2011

Blood, urine and bile concentrations of carbenoxolone have been measured after oral dosage to patients. The compound is rapidly absorbed attaining high blood concentrations and, as with rats, is excreted mostly in the bile, with only traces (2% of the dose) appearing in the urine. Blood concentrations of the drug generally exhibit two maxima, at 1–2 and 3–6 h after dosage, which are taken to indicate enterohepatic circulation of the biliary-excreted conjugates. As absorption of orally administered carbenoxolone is so rapid and does not occur when the gastric contents have pH >2, it is inferred that the major site of absorption is the stomach. The high blood concentrations of carbenoxolone (60% of the dose present in the blood) are probably due to a high degree of binding of the drug to the plasma proteins. In contrast to the rat, in which carbenoxolone is largely hydrolysed to β-glycyrrhetic acid before absorption, in man carbenoxolone is absorbed largely unchanged and is excreted in the bile as the glucuronide. Gastric absorption of carbenoxolone may be necessary for the increased production of gastric mucus observed with the drug and hence is necessary for its gastric ulcer-healing activity.
The effect of nialamide, pargyline and tranylcypromine on the removal of amphetamine by the perfused liver
Authors: Trinker Fedora R , Rand M J
Published: April 2011

Nialamide, pargyline and tranylcypromine, three monoamine oxidase inhibiting drugs, and the microsomal enzyme inhibitor SKF 525-A significantly decreased the amount of amphetamine removed from the portal circulation of the isolated perfused liver of the cat. The enhancement of the vascular actions and toxicity of amphetamine by monoamine oxidase inhibitors could be explained in terms of these findings.
The effects of temperature on the critical micelle concentrations of alkyl α-picolinium bromides
Authors: Adderson J E , Taylor H
Published: April 2011

The temperature dependence of the critical micelle concentrations of decyl, dodecyl and tetradecyl α-picolinium bromides has been determined by measurement of conductance. Constants for the equation relating log. CMC and alkyl chain length have been calculated for the temperature range 5° to 70°, in increments of 5°. An estimate of the effect of temperature upon the degree of counterion binding is recorded. Thermodynamic parameters have been calculated using the uncharged phase-separation model and a theoretical interpretation of the process of micellization given.
Moisture uptake and tensile strength of bulk solids
Authors: Eaves T , Jones T M
Published: April 2011

An apparatus is described in which bulk solid handling properties can be examined over a wide range of humidities. It is shown that constant temperature and relative humidity can be maintained. The apparatus can also be used to study the effect of cycles of humidity changes. The rate of moisture uptake by loosely packed and tapped beds of six pharmaceutical materials was found to be dependent upon bed depth but independent of bulk density. The tensile strengths of the bulk solids changed when they were subjected to high relative humidities.
Salicylate and enzymes
Authors: SMITH M J H , DAWKINS P D
Published: April 2011

Salicylate inhibits the activities of a number of cellular enzymes and in some instances the mechanisms of inhibition have been established (Smith, 1968a). Reported inhibitory actions of the salicylate ion on important enzyme systems in vitro are now reviewed and assessed in relation to the known clinical and toxic effects of the drug.
The significance of differences in the potency of enantiomers of anti-acetylcholine drugs
Authors: BRIMBLECOMBE R W , INCH D M GREEN T D , THOMPSON PAMELA B J
Published: April 2011

The anti-acetylcholine potencies of the dimethylaminoethyl and N/-methyl piperidin-4-yl esters of R and S 2-cyclohexyl-2-hydroxy-2-phenylacetic acid and their quaternary derivatives have been measured by in vitro and in vivo procedures. The R-enantiomer of dimethylaminoethyl-2-cyclohexyl-2-hydroxy-2-phenylacetate was approximately 100 times more active than the corresponding S-enantiomer both in vivo and in vitro. In contrast, the differences in potencies of the enantiomers of the other compounds were smaller in vivo than in vitro and moreover, the in vivo differences in potency decreased as the potency of the racemates increased. The relevance of these results to general studies of enantiomeric differences is discussed.
The self-association in aqueous solutions of morphine sulphate and some related salts
Authors: PERRIN J H , ISHAG A
Published: April 2011

Conductivity and optical rotatory dispersion investigations suggest that morphine sulphate and some related salts aggregate in aqueous solution. This association is probably due to the stacking of the aromatic rings.
The identification of tablets and capsules containing barbiturates by MATR infrared spectroscopy
Authors: ATKINSON J E
Published: April 2011

The technique of MATR infrared spectroscopy has been used to record the infrared spectra of a variety of barbiturate-containing tablets and capsules. The production of different spectra for preparations containing different active ingredients, and the absence of spectral variations arising from the source of manufacture and the presence of tablet and capsule additives, indicate the technique to have possible application in the identification of tablets and capsules, especially where only small samples (1–2 mg) are available.
The gas-liquid chromatographic estimation of phenacetin and paracetamol in plasma and urine
Authors: PRESCOTT L F
Published: April 2011

Methods are described for the gas-liquid chromatographic estimation of phenacetin and paracetamol in plasma and free and conjugated paracetamol in urine. p-Chloracetanilide and p-bromacetanilide were used as internal standards. The drugs were extracted with ethyl acetate and before chromatography were converted to trimethylsilyl derivatives with N,O-bis(trimethylsilyl)acetamide (simultaneous assay of phenacetin and free paracetamol in plasma), or N-trimethylsilylimidazole (assay of paracetamol alone). Phenacetin was extracted with chloroform and chromatographed directly. Paracetamol glucuronide and sulphate were hydrolysed enzymatically to the parent compound before extraction. Recovery of added phenacetin and paracetamol in plasma at concentrations of 1–100 μg/ml was complete, and the limit of detection of the drugs in plasma was 0.05 μg/ml.
The sizing of some powder and liquid sprays from pressurized packs by air sedimentation
Authors: HIRST CHRISTINE A , KAYE R C
Published: April 2011

The construction and testing of an apparatus suitable for the size analysis of certain pressurized sprays by air sedimentation is described. Talc spray size was related to the size of the talc used to prepare the pressurized pack. For other powders (UFI and neomycin sulphate) the sprays were much larger than the powder used to prepare the pack. The use of propellents of higher vapour pressures, higher pack temperatures and the addition of 0·5% sorbitan monolaurate resulted in smaller talc sprays. Talc spray size was increased by the addition of 0·5% isopropyl myristate. Increasing the viscosity of the liquid product and increasing the concentration of propellent gave a reduction in liquid spray size; for both liquid and talc sprays, smaller sprays resulted from the use of a valve housing with a vapour tap.
Effects of acetylsalicylic acid on serum protein binding and metabolism of tryptophan in man
Authors: SMITH HEATHER G , LAKATOS CLAIRE
Published: April 2011

In normal persons, ingestion of aspirin causes a release of tryptophan from its binding site on serum albumin. There is a fall in bound and total serum tryptophan concentrations and a rise in free tryptophan concentrations. The urinary excretion of 3-hydroxyanthranilic acid is decreased, that of xanthurenic acid is increased and that of 3-hydroxykynurenine was increased in 4 out of 6 subjects, indicating an effect on the enzyme systems involved in the metabolism of tryptophan. Conjugates of these metabolites were shown to interfere with the method of assay of the unconjugated hydroxy acids by column chromatography. To overcome this difficulty all urine samples were first boiled in molar hydrochloric acid to hydrolyse any conjugates present. Any results obtained using non-hydrolysed urines would be misleading. This work shows that it is important to take account of the drugs used in treatment before ascribing changes in tryptophan metabolism to pathological states.
Mass spectrometry of fluorinated corticosteroidal 1,4-dien-3-ones of the British Pharmacopoeia
Authors: LODGE B A , TOFT P
Published: April 2011

The mass spectrum of each of the B.P. 1968 fluorinated corticosteroidal 1,4-dien-3-ones is shown to be sufficiently characteristic to be of value as a means of identification. Mechanisms for the principal fragmentations are discussed.
Modifications of the responses to antidiuretic hormone by hydrolytic enzymes
Authors: CUTHBERT A W , PAINTER M E
Published: April 2011

Proteolytic enzymes (trypsin and α-chymotrypsin) and lipolytic enzymes (phospholipases A & C) have been used to treat both surfaces of the skins of frogs and toads. The effects of the enzymes on sodium transport (frog skin) and hydraulic flow (toad skin) have been measured, together with the effects on the responses to ADH. With the experimental conditions used, proteolytic enzymes reduced resting sodium transport but had no major effect on the responsiveness to ADH. Conversely these enzymes had no effect on resting hydraulic flow but reduced or abolished the responses to ADH. Phospholipases applied to the inner surfaces of skins affected neither water nor sodium movement but abolished the responses to ADH. Phospholipases applied to the outside enhanced the effect of ADH on water flow but had no effect on the increased sodium movement caused by ADH. The results are discussed in terms of the possible removal of calcium binding sites by phospholipases.
Uptake and metabolism of β-phenethylamine and tyramine in mouse brain and heart slices
Authors: ROSS S B , RENYI A L
Published: April 2011

Tritium labelled β-phenethylamine and tyramine were incubated with slices of mouse brain and heart. Cocaine (3 × 10−5M) caused a reduction of 30% in the uptake of tyramine as well as in the formation of its metabolite 4-hydroxyphenylacetic acid. Cocaine had no effect on either the uptake of phenethylamine nor its deamination to phenylacetic acid.
The influence of compression and formulation on the hardness, disintegration, dissolution, absorption and excretion of sulphadimidine tablets
Authors: VAN OUDTSHOORN M C B , POTGIETER F J , DE BLAEY C J , POLDERMAN J
Published: April 2011

Sulphadimidine tablets were prepared with different binding agents and compressed at different compression levels, ranging from 200–2000 MNm2. The disintegration time and dissolution rate of the different tablets were determined. Tablets formulated with gelatin or starch mucilage and compressed at 600 MNm2 were selected for in vivo experiments using a urinary excretion method. Although both tablets complied with the disintegration requirements of the British Pharmacopoeia, dissolution rate and urinary excretion showed a difference in availability of drug from the two tablets.
The structure of buckwheat, Fagopyrum esculentum Moench
Authors: MCCLEMENT JUNE , JACKSON BETTY P
Published: April 2011

The morphology and anatomy of the aerial parts of Fagopyrum esculentum have been described and the most important microscopical characters of value in the identification of commercial Buckwheat have been indicated.
The polymorphism of sulphathiazole
Authors: MESLEY R J
Published: April 2011

The existence of two species of the low temperature form of sulphathiazole, postulated by Moustafa & Carless (1969) and by Shenouda (1970), has been confirmed. Contrary to the opinions of these workers it is concluded that these are two distinct forms having different lattice structures which give rise to distinguishable X-ray diffraction patterns and infrared spectra. The fact that commercial samples frequently contain both forms casts doubt on the validity of previous solubility measurements and on the use of differential scanning calorimetry as an assay procedure for the low temperature form.
Determination of N-(2-benzoyloxyethyl)-norfenfluramine (JP 992) and its metabolites in urine
Authors: BECKETT A H , SHENOY E V B , BROOKES L G
Published: April 2011

A gas-liquid chromatographic method of determination of norfenfluramine and N-2-hydroxyethylnorfenfluramine is described. Also a method is reported to determine N-(2-benzoyloxyethyl)norfenfluramine and its metabolites containing the m-trifluoromethyl- benzyl and -benzoyl moieties in urine, by oxidation of these to m-trifluoromethyl benzoic acid followed by methylation and gas-liquid chromatography.
Cell culture as a test system for toxicity
Authors: METCALFE SUSAN M
Published: April 2011

Appropriate cell culture systems provide a useful additional method of screening for toxicity, in spite of the obvious problems of relating in vitro effects of test compounds at the cellular level to their effects in the whole animal. It is shown that a wide range of chemically disimilar molecules have a reversible inhibitory activity on the growth of primary cultures of monkey kidney cells. The potency of these compounds correlates with their lipid solubility, suggesting that the cell membranes may be their main site of action. Support for this is obtained by the correlation of inhibitory activity and the ability of the same compounds to stabilize the erythrocyte membrane against hypotonic haemolysis which is known to be a direct effect of interaction with the erythrocyte membrane. It is suggested that the ability of the food additive butylated hydroxytoluene to act as a potent inhibitor of cellular growth may account for its reported ability to prolong the life span of mice.
Some aspects of the metabolism of morphine-N-oxide
Authors: HEIMANS R L H , FENNESSY M R , GAFF G A
Published: April 2011

After administration of morphine-N-oxide (MNO) to rats the opiates appearing in the urine were morphine (61%) and MNO (39%). After administration of morphine, the urinary opiates were morphine (80%) and normorphine (20%). When tacrine was given with morphine the urine also contained MNO (46% of total urinary opiates) and the amount of normorphine was much decreased (to 1%), the remainder being morphine (53%). Tacrine and amiphenazole inhibited demethylation of morphine and codeine by a rat liver fraction in vitro. MNO had weak inhibitory activity. Neither MNO nor codeine-N-oxide were demethylated in vitro.
The metabolism and binding of [14C]mycophenolic acid in the rat
Authors: NERY R , NICE E
Published: April 2011

Seventeen h after the intraperitoneal administration of 33 mg/kg of [14C]mycophenolic acid to rats, radioactivity was bound to the tissues of the intestines, bladder, stomach, kidney, liver and lung in decreasing order; no binding to spleen tissue was observed. In vitro incubations of the agent with macromolecules resulted in the binding of radioactivity to salmon sperm DNA and to bovine plasma albumin, the extent of binding being increased and decreased, respectively, in the presence of a rat liver microsomal system. The binding was apparently covalent since repeated purification procedures failed to release the bound radioactivity; heating of [14C]mycophenolic acid bound-DNA in n hydrochloric acid at 100° for 2 h caused the release of the bound radioactivity. Under the conditions described, 43% of the administered radioactivity was excreted in the urine (33%) and faeces (10%); the urine contained free mycophenolic acid (13%), mycophenolic acid glucosiduronate (17%) and an uncharacterized metabolite (3%).
The relation between biological activity and the degree of resolution of optical isomers
Authors: BARLOW R B , FRANKS FIONA M , PEARSON J D M
Published: April 2011

Previous reports of the low stereospecificity of benzhexol can be ascribed to inadequate resolution of the samples tested and a report of much higher stereospecificity has been confirmed. The two enantiomers have been found to differ over 1000-fold in their affinity for the postganglionic acetylcholine receptors of the guinea-pig ileum. Mixtures of the enantiomeric forms of phenylcyclohexyl-glycolloylcholine and of benzhexol have been tested on this preparation and the dose-ratios used to calculate apparent affinity constants. With both pairs the results indicate that the two enantiomers compete with the agonist and with each other and justify the use of the stereo-specific index to set limits to the degree of resolution. For compounds such as these, in which one enantiomer has appreciably higher biological activity than the other, this biological method for assessing stereochemical purity is likely to be at least as satisfactory as any nuclear magnetic resonance method currently in use, because of the very great sensitivity of the stereospecific index to the degree of resolution.
Localization of [3H]pimozide in the rat brain in relation to its anti-amphetamine potency
Authors: SOUDIJN W , VAN WIJNGAARDEN I
Published: April 2011

The pharmacological activity of the neuroleptic agent pimozide is well correlated with the concentration of [3H]pimozide in the brain of the Wistar rat. There is an enhanced uptake and retention of [3H]pimozide in the caudate nucleus, an area in which amphetamine and apomorphine act. Its concentration in the caudate nucleus is not correlated with its anti-apomorphine and anti-amphetamine potency. There are, however, significant shifts in the subcellular distribution of [3H]pimozide in the caudate nucleus, from the mitochondrial fraction to the fraction consisting mainly of submicroscopic nerve endings. These shifts correlate well with its pharmacological activity. This points to the small nerve-endings as being the site of action of pimozide. The drug does not influence either the penetration of (+)-[14C]amphetamine into the brain, or its metabolism, indicating that the anti-amphetamine action cannot be due to a decreased penetration of amphetamine into the brain, although a subcellular redistribution of amphetamine induced by pimozide cannot be excluded.
A modification of rat adjuvant arthritis for testing antirheumatic drugs
Authors: MIZUSHIMA Y , TSUKADA W , AKIMOTO T
Published: April 2011

An inflammation having an acute and a prolonged phase was induced by the injection of carrageenan into the paw of rats inoculated with adjuvant 6 days previously (adjuvant-carrageenan-induced inflammation, ACII). Steroidal and acidic non-steroidal anti-inflammatory drugs were effective on both phases. Basic non-steroidal antiinflammatory drugs were effective only on the acute phase, and cytotoxic drugs only on the prolonged phase. Neither gold nor chloroquine preparations inhibited either phase. Effectiveness of drugs on the acute phase was similar to that on carrageenan oedema. Inhibitory effects of drugs on the prolonged phase were similar to those on the secondary lesions of adjuvant arthritis. The ACII test is considered to have advantages compared with the adjuvant arthritis test in duration of drug administration, in the measurement of intensity of inflammation, in the time for experiment and in analysing the action of drugs.
A new spectrophotometric method for the determination of penicillins
Authors: BUNDGAARD HANS , ILVER K
Published: April 2011

A rapid and convenient method is described for the determination of nine commonly used penicillins. This is based on the spectrophotometric measurement at 325–345 nm of penicillenic acid mercuric mercaptides of the penicillins, formed in quantitative yield on heating at 60° or on standing at 20° in a 1·2 m imidazole and 10−3 m mercuric chloride solution at pH 6·8. The method, which permits detection of concentrations of penicillins down to 0·5 μg/ml, is reproducible. Since the intact penicillin molecule is required for the penicillenic acid formation, the method is highly specific and useful as a means of assessing stability.
Titrimetric determination of sulphate in pharmaceutical products
Authors: ROETS E , VANDERHAEGHE H
Published: April 2011

A method is described for the titrimetric determination of sulphate in pharmaceutical products. After fixation of the base on a cation exchange resin column, sulphuric acid was titrated with barium chloride in the presence of thorin indicator. The titrimetric method was compared with the gravimetric method.
The effect of intra- and extragranular maize starch on the disintegration of compressed tablets
Authors: SHOTTON E , LEONARD G S
Published: April 2011

The effect of maize starch on the particle sizes recovered from sulphadiazine tablets subjected to the B.P. disintegration test has been examined. A size analysis of the resulting suspension was made using a combination of wet sieving techniques and the Coulter Counter. Intragranular starch resulted in the recovery of finer particles than when extragranular starch was used, but the disintegration time was longer with intragranular starch. The use of both intra- and extragranular starch in a tablet gave intermediate disintegration time and mean diameter.
Determination of thermodynamic dissociation constants of local anaesthetic amines: influence of ionic strength
Authors: LEVY RENÉ H , ROWLAND MALCOLM
Published: April 2011

Theoretical calculations, based on the Debye-Hückel theory, indicate that for weak monoprotic bases that do not involve a hydroxyl group (B) a stoichiometric pKa determined at any ionic strength compatible with an accurate determination (μ <0·10) should be no different from the thermodynamic pKa. The pKa's of two local anaesthetic amines were determined at several ionic concentrations. The resultant independence of the acidic dissociation constants on ionic concentration supports the theoretical considerations. The implications of these results in local anaesthetic research are discussed.
Determination of zinc in pharmaceutical preparations by atomic absorption spectrophotometry
Authors: MOODY R R , TAYLOR R B
Published: April 2011

The analysis for Zn content of a variety of pharmaceutical preparations by atomic absorption spectrophotometry is recorded. The method for creams, ointments and pastes involves extraction with ether, dissolving the residue in HCl, followed by suitable dilution of the extract to bring the Zn content within the limits of the calibration graph, and measurement of the Zn content using the 213·9 nm resonance line. For lotions and dusting powders the initial ether extraction is neglected; for liquid preparations a simple dilution is required. The method showed a good degree of accuracy and precision and was specific for Zn no interference being encountered from a variety of metals and other common excipient materials that are used in pharmaceutical preparations.
An improved in vivo procedure for standardization of heparin preparations
Authors: KUO S H , JAQUES L B , MILLAR G J
Published: April 2011

The WHO International Collaborative Study of the Assay of Heparin has demonstrated the unreliability of present assay methods for heparin. An in vivo assay procedure has been redesigned to use standardized dogs in a crossover assay, measuring three coagulation tests and lipoprotein lipase on nine blood samples for each heparin dose. The procedure was tested with five heparin preparations. By the standard method for parallel line assays regression was significant (P > 0·001) for log2 dose-log10 response. Analyses of variance were satisfactory and estimation of potency statistically valid. The potency of each heparin in International units varied with the parameter used. Fiducial limits were ±10% for anticoagulant parameters, ±15% for antilipaemic parameter and reproducibility, 97% for anticoagulant parameters, 87·5% for antilipaemic parameter.