bluuebunny/crossref_metadata_2025 huggingface dataset:
An experimental approach to long-lasting hypotensive eledoisin-like peptides
Authors: BERNARDI L , DE CASTIGLIONE R , FREGNAN G B , GLÄSSER A H
Published: April 2011

A new series of eledoisin-like peptides was synthesized with the object of obtaining long-lasting hypotensive drugs. Acyl residues were introduced into the molecule of the peptide

They were dissolved in some polar solvents (water, diacetin, triacetin, dimethyl-sulphoxide), and injected intramuscularly into either anaesthetized or unanaesthetized dogs. Comparison was made with eledoisin dissolved both in water and diacetin. Some of the peptides, mainly the butyryl and valeryl derivatives, in diacetin had a significantly longer-lasting action. The intensity of the hypotension could be also reduced, to avoid side-effects in unanaesthetized dogs, but it was not possible to make it gradual.
Methaemoglobin formation induced by aromatic amines and amides
Authors: McLEAN S , MURPHY B P , STARMER G A , THOMAS J
Published: April 2011

Two series of anilides have been examined for their ability to induce the formation of methaemoglobin in cats. The first series is one in which the aniline was acylated by a series of acids and the second is one in which alkyl groups were substituted on the benzene ring and the acyl moiety kept as the acetyl group. In neither series was any correlation found between the methaemoglobin-forming ability and stability of the amide group. In the first series, as the size of the acyl group was increased so the activity rose to a peak and then declined. It is suggested that this phenomenon is related to absorption of the compounds from the gastrointestinal tract. In the second series a parallelism in response was observed between amides given orally and the corresponding amines administered intravenously, suggesting that the nature of the amine liberated on hydrolysis is the major determining factor in the methaemoglobin forming ability of amides.
A method for the quantitative determination of the total concentration of radiopaque agents in plasma
Authors: DE MIRANDA J F RODRIGUES , PETERS J C M , VAN RENS A M F P
Published: April 2011

The total concentration of radiopaque agents in plasma can be determined spectrophotometrically after elimination of interfering factors using a double column filled with cross-linked dextran-gel Sephadex G-25c and Se-Sephadex 25c. The method gives a linear relationship between the total concentration in the sample and the maximum concentration in the eluate and is sensitive to about 50μg/ml of radiopaque agent.
The bioassay of γ-aminobutyric acid using a muscle preparation from Ascaris lumbricoides
Authors: ASH A S F , TUCKER J F
Published: April 2011

A method is described for the assay of γ-aminobutyric acid based on inhibition of the isolated dorsal muscle of Ascaris lumbricoides. The degree of relaxation produced by the acid was linearly related to the logarithm of the dose (0.5–2.0 μg/ml). Analyses of variance and indices of precision, calculated from the results of 6 model assays, indicated a satisfactory assay procedure. Ascaris was much more sensitive to γ-aminobutyric acid than to related amino-acids and was unaffected by dopa, dopamine, adrenaline, noradrenaline, 5-hydroxytryptamine or histamine (2 mg/ml) and by bradykinin (50 μg/ml).
Desipramine and amphetamine metabolism
Authors: CONSOLO S , DOLFINI E , GARATTINI S , VALZELLI L
Published: April 2011

Desipramine (2.5–5 mg/kg) increases the urinary excretion of amphetamine given intraperitoneally at doses of 7.5–15 mg/kg and it decreases the excretion of p-hydroxyamphetamine. The rate of removal of brain amphetamine is decreased by desipramine (5 mg/kg, i.p.) when amphetamine is injected intraperitoneally but not when it is injected intracerebrally. It is suggested that desipramine impairs the hydroxylation of amphetamine in the liver thereby increasing the level of circulating amphetamine and eventually of brain amphetamine.
Degraded and undegraded carrageenans and antipeptic activity
Authors: ANDERSON W , HARTHILL J E
Published: April 2011

The antipeptic activities of a series of undegraded κ- and Λ-carrageenans and degraded carrageenans have been examined by two methods. The activities differ quantitatively. Compared with the κ-carrageenans, the Λ-carrageenans, as a group, have greater activity and this is associated with low 3,6-anhydro-d-galactose and high ester sulphate content. Within the series of undegraded carrageenans, both κ and Λ, differences in antipeptic activity are significantly and positively related to differences in sulphate content. In addition to the effect of sulphate, 3,6-anhydrogalactose content appears to be inversely related to activity but in the Λ-series only; differences in viscosity are without effect. Initial degradation without loss of sulphate resulted in loss of activity but further degradation, also without loss of sulphate did not reduce activity further. Antipeptic activity appears to depend on a combination of structural features of which the differences between κ-Λ carrageenans, molecular size and polyanionic properties are aspects.
The influence of 1-hexadecanol on the acid-catalysed hydrolysis of sodium dodecyl sulphate
Authors: BARRY B W , SHOTTON E
Published: April 2011

The kinetics at 60° of the acid-catalysed hydrolysis of sodium dodecyl sulphate in the presence of 1-hexadecanol above the critical micelle concentration showed the hydrolysis to be first order and the rate to depend on the molar ratio of alcohol to alkyl sulphate. Up to a ratio of 0.75 the rate increases; above this there is a steady decrease. The changes in rate have been correlated with phase changes and explained on the basis of the effect on the charge density on the micelle, and on the dielectric constant of the associated medium, in passing from a mixed spherical micelle to the lamellar structure and then to the expanded lamellar structure prevailing in liquid crystals.
Abortifacient and toxic actions of the glycoside ‘albitocin’ extracted from some Albizia species
Authors: LIPTON A
Published: April 2011

Conscious intact mice, rats, guinea-pigs, rabbits and monkeys were dosed with “albitocin”, an active glycoside extracted from plants of certain Albizia species used by East African native doctors to accelerate labour and procure abortion. In pregnant animals abortion usually occurred within 12 hr at dose levels characteristic for each species irrespective of stage of gestation. In larger doses the drug was toxic, and with lethal doses animals survived 12–170 hr, with increasing apathy and anorexia, conscious but moribund as death approached. Toxicity in the orally dosed animals was lower than in those dosed intraperiotoneally or intravenously. The changes observed which could account for the mortality are discussed.
The antibacterial action of crystal violet
Authors: ADAMS E
Published: April 2011

Crystal violet has an antibacterial action against Escherichia coli, Staphylococcus aureus, Streptococcus faecalis and Bacillus subtilis. The effect of the dye, measured as minimum inhibitory concentration or retardation of growth, increases as the pH rises from 6 to 8. Of the four species E. coli is most resistant to the dye; the resistances of the other organisms are similar. The mode of action put forward by Steam & Stearn (1928) that the action of crystal violet is due to the formation of an unionized complex of bacteria with dye, is supported. Gram-negative organisms, such as E. coli, have high isoelectric points and contain less acidic components than Gram-positive bacteria which usually have lower isoelectric points, so the former combine with crystal violet less readily and are more resistant to the dye. In extension of this theory, the negative charge on bacteria is increased as the pH of the medium is increased, and the organisms become more sensitive to dye. Evidence is presented which refutes the theory of a poising of the redox potential by crystal violet suggested by Dubos (1929) and Ingraham (1933).
The mechanism of the inhibition of dehydrogenases by salicylate
Authors: DAWKINS P D , GOULD B J , STURMAN J A , SMITH M J H
Published: April 2011

Salicylate inhibits rabbit muscle lactate dehydrogenase, horse liver alcohol dehydrogenase, pig heart malate dehydrogenase and pig heart isocitrate dehydrogenase in vitro. The inhibitions are reversible, involving competition with nad, nadh2 or nadp. The results are discussed with reference to some of the in vivo actions of the drug.
Histamine release from the mast cells of guinea-pig lung
Authors: EILBECK J F , SMITH W G
Published: April 2011

The distribution of mast cells and the effects of antigen on the mast cell population of sensitized guinea-pig lung have been examined. Doses of antigen, phospholipase A, trypsin, and compound 48/80 which released similar amounts of histamine also caused mast cell damage to similar extents following in vitro or in vivo administration. Pretreatment with ethanolamine, hydrocortisone or theophylline reduced the release of histamine and of srs-a, and mast cell damage during subsequent anaphylaxis. Whilst there is evidence that the mast cell might be a selective target for the anaphylactic reaction in guinea-pig lung tissues, there is also evidence to suggest that the anaphylactic reaction induces generalized cell damage in these tissues.
The tissue distribution and metabolism of amidopyrine in the rat and pregnant and non-pregnant rabbit
Authors: BERTÉ F , BENZI G
Published: April 2011

The tissue distribution of amidopyrine and its metabolites 4-amino-antipyrine and N-acetyl-4-amino-antipyrine has been determined at intervals following oral doses of 300 mg/kg of amidopyrine in pregnant, non-pregnant and foetal rabbits, and also in adult non-pregnant rats. Except in lung, their concentration was higher in the normal rabbit than the rat. In both species amidopyrine levels were maximal at 2 hr, but the metabolite levels varied with tissue, species and time interval. The dominant pathways were demethylation in the rabbit and acetylation in the rat. Plasma and tissue levels of amidopyrine were higher in non-pregnant than pregnant rabbits, whereas those of the metabolites varied. Studies indicate that 25-day, but not 14-day foetuses may metabolize amidopyrine.
Antagonism of anti-inflammatory drugs on bradykinin-induced increase of capillary permeability
Authors: MARTELLI E ARRIGONI
Published: April 2011

Phenylbutazone, sodium salicylate, calcium acetylsalicylate and sodium mefenamate each antagonize the bradykinin-induced increase of capillary permeability in the rat paw. The method described was not affected to any extent by urethane anaesthesia nor by mecamylamine, papaverine, reserpine or chlorothiazide. Hexobarbitone partially inhibited the bradykinin effect, as did bretylium and acetic acid.
Acetylcarbocholine and acetylsilicocholine: Directly or indirectly acting cholinergic spasmogens?
Authors: Henderson P TH , Ariëns E J , Ellenbroek B W J , Simonis A M
Published: April 2011

The cholinergic and anticholinergic actions of nitrogen-free isosteres of acetylcholine and benzilylcholine are described. Esters of two kinds of choline analogues, carbocholine and silicocholine, were used. The spasmogenic activity of acetylcarbocholine and acetylsilicocholine on the guinea-pig ileum was identified as an indirect cholinergic action, in contrast to the direct cholinergic action of furtrethonium and the mainly non-cholinergic action of barium ions. In addition to this indirect cholinergic action, both esters show a weak anticholinergic and a weak noncompetitive “papaverine-like” spasmolytic activity. The corresponding benzilyl esters, although without an onium group, are relatively potent anticholinergic compounds.
Subcellular distribution of [3H]ε-aminocaproic acid and its effects on amine storage mechanisms
Authors: Stitzel Robert , Lundborg Per , Obianwu Hopé
Published: April 2011

ε-Aminocaproic acid (EACA) is an amino-acid reported to cause almost complete depletion of cardiac noradrenaline stores. The present report indicates that this compound can be found in both the particulate and supernatant fractions derived from heart homogenates. The [3H]EACA in the supernatant probably represents a mixture of intra- and extraneuronally located drug. Protriptyline pretreatment decreases the uptake of [3H]EACA suggesting that the amino-acid probably utilizes the amine membrane transport system, EACA, like reserpine, can both impair the retention of exogenously administered amines by adrenergic storage particles and cause the release of amines previously stored in such particles.
The chromatographic analysis of spermaceti
Authors: Holloway P J
Published: April 2011

The alkyl esters of spermaceti can be analysed directly by high temperature gas chromatography on a 10% Silicone Elastomer E301 column following the injection of the whole wax. The validity of the technique was established by initial chromatographic work on the isolated alkyl ester fraction and its saponification products. In three commercial wax samples, four homologues C28 (hexadecyl dodecanoate), C30 (hexadecyl tetradecanoate), C32 (hexadecyl hexadecanoate) and C34 (hexadecyl octadecanoate), accounted for 86–89% of the total alkyl esters. Variation in the ester homologue content is produced only by variations in the fatty acid homologue content.
Some pharmacological effects of 1, 2, 3, 4-tetrahydro-2-naphthylamine (β-tetra) and its secondary N-alkyl derivatives
Authors: Pennefather Jocelyn N
Published: April 2011

Some effects of 1, 2, 3, 4-tetrahydro-2-naphthylamine (β-tetra, β-tetrahydronaphthylamine, 2-aminotetralin) and four of its secondary N-alkyl derivatives on blood pressure in the cat and in the pithed rat are described. Pressor responses were obtained with β-tetra in both preparations. The introduction of an β-methyl group to form 1, 2, 3, 4-tetrahydro-2-naphthylmethylamine led to a decrease in pressor potency in both species. The substitution of higher alkyl groups yielded compounds which were depressor in the cat and had markedly reduced pressor potency in the pithed rat. Increases in substituent chain length resulted in slight decreases in adrenaline-blocking potency and slight decreases in the tendency of the compounds to depress breathing. Experiments with β-tetra in reserpine-treated, adrenalectomized and hexamethonium-treated animals led to the conclusion that the pressor effect of 1, 2, 3, 4-tetrahydro-2-naphthylamine is mediated by an action at the sympathetic neuron resulting in the release of noradrenaline.
Mass spectra of derivatives of phenylalkylamines
Authors: Reisch J , Pagnucco R , Alfes H , Jantos N , Möllmann H
Published: April 2011

The mass spectra of 18 synthetic and naturally occurring phenylalkylamine derivatives and compounds having a similar pharmacological effect were taken and evaluated and possible fragmentation mechanisms for each are discussed.
Actions of phencyclidine on the perfused rabbit ear
Authors: O'donnell Stella R , Wanstall Janet C
Published: April 2011

Phencyclidine potentiated the responses of the rabbit perfused ear and its isolated central artery to noradrenaline, adrenaline and periarterial nerve stimulation. The potentiation of nerve stimulation was more pronounced than the potentiation of exogenous noradrenaline or adrenaline. Where the access of noradrenaline was restricted to one surface of the artery only, phencyclidine caused a much greater potentiation of extraluminal than of intraluminal noradrenaline. A biphasic response to tyramine was observed, the secondary prolonged vasoconstrictor phase being blocked by phencyclidine. It is postulated that phencyclidine inhibits the uptake of both noradrenaline and tyramine by the adrenergic axons in the blood vessel wall in a manner similar to that suggested for cocaine.
Effect of desipramine injected intracerebrally in normal or reserpinized rats
Authors: Rewerski W , Jori A
Published: April 2011

Desipramine, 7·5–30 μg in 1 μl, injected under stereotaxic control into the brain of rats elicits a moderate hyperthermic response. This effect is more marked in animals made hypothermic by a previous treatment with reserpine. The response is not specific for any one of the six brain areas investigated (anterior part of the hypothalamus; nucleus rhomboideus thalami; third ventricle; posterior part of the hypothalamus; lateral part of the area amygdaloidea basalis; and lobus frontalis).
Infrared identification of barbiturates with particular reference to the occurrence of polymorphism
Authors: Mesley R J , Clements R L
Published: April 2011

Infrared spectra of twelve substituted barbituric acids, in a total of 34 polymorphic forms, have been compared. Comparison of a sample spectrum with that of an authentic specimen provides a reliable means of identification, provided that both are in the same crystalline form. To ensure consistent production of a single form a specific treatment is recommended for each substance exhibiting polymorphism.
Effect of electrolytes on coacervation of the systems gelatin—water—ethanol and gelatin—water—sodium sulphate
Authors: Nixon J R , Khalil Saleh A H , Carless J E
Published: April 2011

In the ethanol system the electrolytes had a suppressive effect on the coacervation of isoionic gelatin, whilst at other pH values the phenomenon was favoured in the presence of polyvalent ions. In the sodium sulphate system the added electrolytes produced insignificant effects. The similarity between the systems studied and the complex coacervating system: gelatin(+)-water-acacia(−) is discussed.
The action of ampicillin on Aerobacter (Klebsiella) aerogenes
Authors: Dean A C R , Smith R W
Published: April 2011

The action of ampicillin (α-aminobenzylpenicillin) on Aerobacter (Klebsiella) aerogenes (NCTC 418, Bact. aerogenes no. 240) has been investigated. Enzymatic destruction of the drug, although a necessary prelude to the growth of the sensitive strain, does not precede growth of resistant strains at concentrations to which they have been “conditioned”. Instead a gradual inactivation occurs throughout the growth cycle. It is concluded that other factors are also involved in resistance. Cloxacillin, which was not destroyed by the cells, had little action on the ampicillin-sensitive strain and did not induce any ampicillin-destroying activity. The results are discussed in terms of the modes of action of penicillins and the origin of the resistance is examined.
Polymorphism of cephaloridine
Authors: Chapman J H , Page J E , Parker A C , Rogers D , Sharp C J , Staniforth Susan E
Published: April 2011

Infrared spectra of Nujol mulls and X-ray powder photographs have shown that cephaloridine can exist in at least six different crystalline forms. The preparation, interconversion and properties of these forms are discussed. Proton magnetic resonance spectroscopy has been used to check their chemical identity.
The influence of emulsifier concentration on the rheological properties of an oil-in-water emulsion stabilized by an anionic soap
Authors: Shotton E , Davis S S
Published: April 2011

The rheological properties of liquid paraffin emulsions stabilized by potassium laurate have been found to be markedly dependent on emulsifier concentration. Reversible aggregation of the emulsion began at 1.0% soap and the more highly aggregated systems demonstrated pseudoplastic flow. A maximum relative viscosity was found at 5.0% soap concentration. The viscosity was dependent on particle size but correction for particle size differences did not alter the viscosity concentration relation. The addition of electrolytes to the emulsion demonstrated the difference between surfactant aggregation and electrolyte aggregation. The latter was explained by the Derjaguin-Verwey-Overbeek theory of colloid stability, whilst the former was only satisfactorily explained by the theory advanced by Cockbain in 1952 involving polymolecular adsorption at the oil-water interface and hydrophobic bonding.
The effect of electrolytes on rigidity and diffusion in gelatin-glycerin gels
Authors: Nixon J R , Georgakopoulos P P , CARLESS J E
Published: April 2011

The effect of electrolytes on the rigidity of and diffusion of dye from gelatin-glycerin gels has been examined. Cations, which might be expected to reduce the rigidity in the ratio of their valency, produced a fall in rigidity in the ratio Na+, 1: Ca++, 1·25:A1+++, 1·57. This approximate halving of the effect is attributed to interference by the chloride ion. The rigidity was proportional to the square root of the ionic concentration except with sodium ferrocyanide where no simple relation held. A simple expression G = G0 (1 ± ***I) was found for the rigidity, the sign depending whether anion or cation was considered. The effect of anions and cations on diffusion was as varied as their effect on rigidity. The addition of chlorides increased the diffusion coefficient in the order Al > Ca > Na. Both multivalent anions examined produced a decrease in diffusion coefficient; the sulphate being less effective than the ferrocyanide.
Influence of 1-(5-methyl-1-phenylpyrazol-4-yl)-3-[4-(o-tolyl)piperazin-l-yl]-propan-1-one hydrochloride (CIBA 1002-Go) on the stores of catecholamine in rat and cat tissues
Authors: Kaul C L , Grewal R S
Published: April 2011

The effect of 1002-Go has been examined on the catecholamine stores in rat heart, brain, adrenals and cat heart. There is a significant reduction in the catecholamine content from all the tissues with doses ranging from 2·5–30 mg/kg. Guanethidine is slightly less potent as a depletor of catecholamine than 1002-Go in the rat. In cats, however, 1002-Go is much weaker than guanethidine or reserpine in depleting the catecholamine stores. There also seem to be differences among these anti-hypertensive agents in the duration of depletion and repletion of the catecholamine stores.
Propranolol uptake into the central nervous system and the effect on rat behaviour and amine metabolism
Authors: Laverty R , Taylor K M
Published: April 2011

Propranolol readily penetrated all areas of the central nervous system after acute intraperitoneal administration and was cleared within 8–16 hr. Propranolol levels in the heart followed a similar pattern. After chronic oral administration brain levels of propranolol were equal to those 3 hr after intraperitoneal injection. Propranolol caused no significant difference in the brain levels of noradrenaline, normetanephrine, dopamine, 3-methoxytyramine, homovanillic acid, 5-hydroxy-tryptamine or total indoles, nor did it cause measurable changes in rat behaviour. An increase by propranolol in sleeping time after chloral hydrate in rats and mice was observed; this effect could not be correlated with changes in brain amine concentrations.
The effect of storage conditions on the heat resistance and heat activation response of Bacillus stearothermophilus spores
Authors: Cook A M , Gilbert R J
Published: April 2011

The heat resistance of spores was unaffected by storage for 52 weeks at 4° or 65 weeks at —16°. However, the magnitude of the heat activation response for heated spores fell with increase in storage time of the unheated spores.
The cathode ray polarography of phenylmercuric nitrate
Authors: Porter G S
Published: April 2011

EXPERIMENTS on the absorption of phenylmercuric nitrate by rubber teats required a simple, rapid and sensitive assay for concentrations of phenylmercuric nitrate from 0·5 to 20·0 μg/ml. Both ultraviolet spectrometry (Eldridge & Sweet, 1956) and chemical methods (British Pharmacopoeia, 1963; Department of Pharmaceutical Sciences Report, 1962) are relatively insensitive, the spectrometric method also being subject to interference by extractive from rubber teats. Ordinary polarographic methods have been used for higher concentrations of phenylmercuric nitrate, two cathodic waves being observed at half-wave potentials of about −0·2 V and −0·9 V respectively. These have been observed in a number of supporting electrolytes, including hydrochloric acid (Page & Waller, 1949), Britton-Robinson buffers (Benesch & Benesch, 1951) and a glycerol-triethanolamine mixture with gelatin (Osborne, 1950).

The cathode ray polarography of phenylmercuric nitrate (0·4–20·0 μg/ml) was therefore investigated in hydrochloric acid (0·1N), lithium chloride (0·2N) and buffer solutions (Britton-Robinson and Sorensen) in the pH range 1·8 to 12·3. In all cases only one wave of analytical importance was seen, the peak voltage being about −0·3 V. Since good linearity, wave shape and sensitivity were found with both 0·2 N lithium chloride and 0·1 N hydrochloric acid, the latter was chosen as supporting electrolyte.
The isolated expansor secundariorum—a smooth muscle preparation from the wing of the domestic fowl
Authors: Buckley G A , Wheater Lynda E
Published: April 2011

Some aspects of the pharmacology of an isolated smooth muscle, the expansor secundariorum, of the domestic fowl have been investigated. Adrenaline, isoprenaline, tyramine and 5-hydroxytryptamine caused the muscle to contract. The responses to adrenaline and noradrenaline were blocked by phentolamine but not by propranolol at a concentration of 1·7 × 10−4M. Tyramine was without effect on the muscle of reserpine treated birds. Cocaine potentiated the effect of noradrenaline but blocked the effects of tyramine. Acetylcholine and histamine had no effect and did not alter the responses of the muscle to noradrenaline. The response to noradrenaline was greater at temperatures below 23° and less at 38°. The muscle contracted rapidly on the addition of Tyrode cooled to 18°. It is concluded that the muscle is wholly innervated by adrenergic postganglionic fibres.
Effect of pretreatment with monoamine oxidase inhibitors or (+)-amphetamine on leptazol convulsions in mice and rats
Authors: Turner T A R , Spencer P S J
Published: April 2011

IT has been claimed that monoamine oxidase inhibitors inhibit the actions of leptazol in experimental animals (Chow & Hendley, 1959; Prockop, Shore & Brodie, 1959; Yen, Salvatore & others, 1962). But other workers have failed to confirm this anticonvulsant action (Kobinger, 1958; Lessin & Parkes, 1959) and some have claimed a proconvulsant effect (Sansome & Dell'Omodarme, 1963; Spoerlein & Ellman, 1961). Reports of the effect of (+)-amphetamine on leptazol convulsions are equally conflicting. Small doses capable of antagonizing electroshock convulsions are described as ineffective against leptazol according to Wolff & Stock (1966), whilst Friebel & Klatt (1959) demonstrated a proconvulsant action. Reserpine enhances the effect of leptazol in animals, the greatest effect appearing to coincide with maximal depletion of tissue amines. If the animals are pretreated with a monoamine oxidase inhibitor before receiving reserpine, however, the subsequent sensitivity of the animal to leptazol is reduced (Pfeifer & Galambos, 1967) or is unaffected (Chen & Bohner, 1961; Spoerlein & Ellman, 1961).

We report initial observations during a re-examination of the interaction between leptazol and five representative monoamine oxidase inhibitors.
Micro-colorimetric determination of adenosinetriphosphatase activity in freeze-dried sections of rat diaphragm muscle
Authors: Buckley G A , Evans R H , Nowell P T
Published: April 2011

A technique is described for determination of ATPase activity in 3–30 μg samples dissected from freeze-dried sections of rat diaphragm muscle. Tissue samples are incubated at room temperature with optimal concentrations of ATP (10 mM) and MgSO4 (5 mM) in 0·1 M tris/HCl buffer at pH 7·4. Inorganic phosphate is measured spectrophotometrically. Mean activity for 20 rats was 0·22 ± 0·06 (s.d.) mole-Pi/kg/wet tissue/15 min. Results did not depend on plane of section or section thickness. 5 mM Mg2+, 10 mM Ca2+ and 1 mM 2, 4-dinitrophenol produced maximal ATPase activation and inhibition was obtained with p-chloromercuribenzoic acid (pI503·9) but not chlorpromazine (0·01–0·1 mM). There was no significant evidence of Na+ plus K+ activated ATPase or inhibition with ouabain (5 mM). ATPase activity was uncharacterized and relative contributions of specified muscle ATPase systems were unknown. As an insoluble enzyme system was involved and photomicrographs showed characteristic muscle features in freeze-dried sections, ATPase activity appeared due to enzymic function in situ. Results are discussed in relation to mutual availability of enzymic sites and reagents.
Coagulation and flocculation in suspensions of griseofulvin and polystyrene latex
Authors: Matthews B A , Rhodes C T
Published: April 2011

Coagulation and flocculation mechanisms have been examined in suspensions of the drug griseofulvin containing anionic surfactants. It has been shown that both mechanisms can give suspensions which are readily redispersible but that flocculation may produce pharmaceutically undesirable effects. The differences between the two phenomena are discussed.
Biological half-lives of [4–14C]testosterone and some of its esters after injection into the rat
Authors: James K C , Nicholls P J , Roberts M
Published: April 2011

Biological half-lives for 14C from labelled testosterone in muscle and whole body of rats have been measured after intramuscular injection of [4-14C]testosterone and its lower esters (formate to valerate). A relation has been observed between ethyl oleate-water distribution coefficients, biological half-lives in the rat and “times of maximum effect” in the rat and fowl.
Some observations on the toxicology of morphine-N-oxide
Authors: Fennessy M R , Fearn H J
Published: April 2011

The intravenous and subcutaneous acute toxicities of morphine-N-oxide (mno) in mice were respectively 3·2 and 8 times less than that of morphine. Amiphenazole or tacrine reduced the acute toxicity of mno but not that of morphine in mice. The chronic toxicity of mno was examined in mice and rats. Daily oral doses of 100 mg/kg did not significantly affect growth or condition, or produce gross or microscopic lesions in mice treated for 3 weeks or rats treated for 3 months. No teratogenic effect of mno or of bromolysergic acid diethylamide was observed in rats.
The chromatographic identification of psychotropic drugs
Authors: Phillips G F , Gardiner Jane
Published: April 2011

The thin-layer chromatography of three classes of psychotropic drugs—phenethylamines, tryptamines and erganes—has been investigated. Published methods are reviewed and Rf data, normalized by a graphical technique, are reported for extensions and modifications of some of these systems. Optimum forensic sorting procedures are recommended.
Buccal absorption and other properties of pharmacokinetic importance of imipramine and its metabolites
Authors: Bickel M H , Weder H J
Published: April 2011

Imipramine and its major unconjugated metabolites have been characterized by their buccal absorption, partition between water and organic solvents—both as a function of pH—and their ionization constants. Furthermore new data are presented on the selective passage of these compounds across the blood brain barrier and on renal excretion as a function of urinary pH in the rat. The shape of the curves of buccal absorption against pH is characteristic for each one of the ten compounds tested and reflects both lipophility of the unionized compound and the pK value. The value of the buccal absorption test for interpreting or predicting pharmacokinetic behaviour of a drug is emphasized.
Effect of Coprinus atramentarius on the metabolism of ethanol in mice
Authors: Coldwell B B , Genest K , Hughes D W
Published: April 2011

The ethanol-soluble material extracted from Coprinus atramentarius was more toxic to mice, as measured by the LD50 and potentiation of the ethanol-induced sleeping time, than the whole mushroom or the residue remaining after ethanol extraction. Also, the ethanol-soluble fraction when fed to mice 4 h before administration of ethanol markedly increased the blood acetaldehyde and ethanol levels.
Detection of drugs with peripheral vascular effects similar to those of nicotinic acid
Authors: Eriksson H E , Norrman S R , Wistrand P J
Published: April 2011

Guinea-pigs anaesthetized with urethane respond with a marked rise in skin temperature due to dilation of the cutaneous vessels after the administration of nicotinic acid. Recording the ear temperature of these animals can therefore be used as a simple and sensitive method for the detection of drugs with peripheral vascular effects similar to those produced by nicotinic acid.
Toxicity of ethanol-barbiturate mixtures
Authors: Wiberg G S , Coldwell B B , Trenholm H L
Published: April 2011

The simultaneous administration of ethanol at doses of either 2, 3, or 4 g/kg intraperitoneally produced a dose-related decrease in the intraperitoneal LD50 for thiopentone, pentobarbitone, amylobarbitone, phenobarbitone and barbitone in rats. The most marked ethanol-barbiturate interaction was with the long-acting, poorly metabolized, less potent barbiturates phenobarbitone and barbitone. Similarly, a non-hypnotic dose of ethanol (3 g/kg, i.p.) produced a much greater prolongation of the sleeping time with non-hypnotic doses of phenobarbitone and barbitone, than with threshold doses of the shorter acting barbiturates. Various postulates are advanced to explain the underlying mechanism of the barbiturate-ethanol interaction.
Monoamine oxidase activities in tissues of thiamine-deficient rats
Authors: Iwata H , Nishikawa T , Fujimoto S
Published: April 2011

The oxidation of monoamine by homogenates of tissues of thiamine-deficient rats was measured with noradrenaline as substrate. Monoamine oxidase activities were depressed in tissues in which the catecholamine content had previously been found raised during thiamine deficiency, with the exception in the cerebral cortex. The impaired enzyme activities were restored to the control level by repeated thiamine injections. An accumulation of pyruvic acid did not inhibit monoamine oxidase activity and thiamine pyrophosphate is not implicated as a co-factor in the oxidation of monoamine substrate.
The rate of dissolution of powdered griseofulvin at different stirring rates
Authors: Elworthy P H , Lipscomb F J
Published: April 2011

The non-ionic surfactant, cetomacrogol, increased the rate of solution of powdered griseofulvin in water. At a stirring rate of 200 rev/min, the increase was similar to that found previously for solid discs of this drug. At 60 rev/min, the surfactant had a smaller effect on the rate of solution.
Quantitative determination of physostigmine from aqueous solution
Authors: Teare F W , Borst S I
Published: April 2011

A gas chromatographic method is described for the direct determination of physostigmine base from a solution of physostigmine salicylate. The method involves isolation of physostigmine salicylate from an aqueous solution by a freeze drying process, subsequent conversion to a trimethylsilyl (TMS) derivative and gas liquid chromatography. The trimethylsilyl salt dissociates on injection into the flash vapourizer inlet of a gas Chromatograph, and the physostigmine-TMS and salicylic acid-TMS derivatives are eluted separately. Due to the specificity of the silylation reaction it is possible to determine by gas chromatography the alkaloid content in the presence of its degradation products. A modification of the method was necessary for the assay of a commercial formulation containing certain additives.
The determination of bromisoval and carbromal in biological material
Authors: Rauws A G
Published: April 2011

The bromine determination (van der Meulen) has been adapted to the assay of bromisoval and carbromal in biological material. Interfering bromide is eliminated by pretreatment with silver nitrate. The ashing procedure was simplified by previous precipitation of proteins by acetone. Interference by bromine-containing metabolites of the drugs is absent or minimal. The method is applicable in the range of 0·1 to 1 μmol. Recovery in blood was 95%. The standard deviation of the determination is approximately 5%.
An automated apparatus for dissolution studies
Authors: Richter A , Myhre B , Khanna S C
Published: April 2011

An automated apparatus for dissolution rate studies of solid dosage forms under sink conditions at constant volume has been developed. Sink condition was maintained in the small volume of the buffer by continuous elimination of the solution and replacement with fresh buffer. A mathematical treatment of the dissolution-dilution system for the apparatus is given. The validity of the calculations has been proved using clomipramine solution and tablets.
Methaemoglobin formation by aromatic amines
Authors: McLean S , Starmer G A , Thomas J
Published: April 2011

Methaemoglobin formation induced in cats by many substituted anilines has been investigated in an attempt to correlate chemical structure with activity. Although no precise relation emerged, some generalizations could be made. 4-Substituents (except methyl and methoxy) increased the activity of aniline. The activity of aniline was either unaltered or reduced by 2- and 3-substituents. Polyhalo-, polymethyl-, methoxy-, ethoxy- and carboxyester substituents reduced activity, and carboxy groups abolished it. Steric effects around the amino-group were not important. The activities of the compounds are discussed in relation to their absorption, distribution, metabolic transformation and the activities of their metabolites.
Prostaglandin E1 action on canine isolated tracheal muscle
Authors: Türker R K , Khairallah P A
Published: April 2011

Prostaglandin E1 (PGE1) inhibits contractions of dog isolated tracheal muscle stimulated by different agents, but the degree of inhibition varies with the agent used. Low concentrations of PGE1 completely block the stimulant effect of 5-hydroxytryptamine, but even large concentrations of PGE1 do not completely antagonize the contractions caused by acetylcholine. The inhibitory effect of PGE1 is blocked by methysergide and not by propranolol, morphine or dihydroergotamine. PGE1 does not relax depolarized smooth muscle, although bradykinin and isoprenaline do. It is concluded that in tracheal smooth muscle, PGE1 interacts with cell membranes close to the 5-hydroxytryptamine D receptors. This causes activation of the smooth sarcoplasmic reticulum, leading to accumulation of calcium ions and relaxation.
Effect of glycopyrronium bromide on basal, and histamine- or gastrin-induced gastric secretion
Authors: Amure B O
Published: April 2011

Acid secretory responses were obtained in rats given either intravenous histamine as dihydrochloride or gastrin subjected to partial purification. A continuous recording method for measuring gastric acid secretion was used. When the rat stomach was perfused with weak sodium hydroxide solution, glycopyrronium bromide (a powerful anticholinergic drug) blocked the acid gastric secretory effects of both histamine and gastrin. Glycopyrronium bromide in doses of 2 μg/100 g body weight of rat is well tolerated. Doses higher than 2 mg/100 g caused respiratory disturbances. The action of glycopyrronium bromide in blocking the gastric secretory effects of gastrin supports the hypothesis that gastrin acts partly by stimulating the vagus nerve.
The effect of 1,1-dimethyl-4-phenyl-piperazinium on the response of mesenteric arteries to sympathetic nerve stimulation
Authors: Malik K U , Ling G M
Published: April 2011

The effect of 1,1-dimethyl-4-phenylpiperazinium (dmpp) on the response to sympathetic nerve stimulation of rat mesenteric arteries perfused with Tyrode solution at a constant flow has been studied. dmpp (0·3 μg/ml) infused for 3 min enhanced the vasoconstriction caused by stimulation. Infusion of the same concentration for 16–40 min greatly reduced the response to nerve stimulation but did not affect the vasoconstrictor response to injected noradrenaline. The blockade of the response to nerve stimulation produced by dmpp was overcome either by adding (+)-amphetamine to the perfusion fluid or by raising the calcium concentration. Neither effect of dmpp was altered by the infusion of atropine. These effects of dmpp were similar to those seen when acetylcholine was added to the perfusion fluid except that the effects of acetylcholine were diminished or abolished by a concentration of atropine much higher than that of acetylcholine. It is concluded that the receptors at the adrenergic nerve terminals are partly muscarinic and partly nicotinic.
Basic dihydromorphanthridinones with anticonvulsant activity
Authors: Waring W S , Whittle B A
Published: April 2011

Some 11-alkylamino-5,6-dihydro-6-oxomorphanthridines and related compounds have been prepared and screened for anticonvulsant activity. One of the more active compounds, 11-dimethylamino-5,6-dihydro-6-oxomorphanthridine (ICI 45,337) was selected for further study and taken to clinical trial in epileptic patients.
The determination of the binding of salicylate to serum proteins
Authors: McArthur J N , Smith M J H
Published: April 2011

The ratios of protein-bound to unbound salicylate in bovine, calf, horse and human sera were measured by equilibrium dialysis, ultrafiltration and frontal elution techniques. The equilibrium dialysis method gave the best measure of binding capacity, but several factors were found to affect the results. These factors include adsorption of the drug onto the dialysing membrane, the composition of the dialysing fluid, the necessity to allow sufficient time for equilibrium to be attained in the presence of serum, and the occurrence of dialysable substances in sera which may either compete with or displace salicylate from its binding sites.
The effect of distribution of magnesium stearate on the penetration of a tablet by water
Authors: Ganderton David
Published: April 2011

Magnesium carbonate powder and granules were compressed and the tablets characterized by their permeability to air and penetration by liquids. To the same materials, magnesium stearate was added, its distribution being varied by varying its concentration, the size of the base material and the method of mixing. The inhibition of penetration by liquids is roughly proportional to the concentration of magnesium stearate and very susceptible to the method of mixing. The influence of granule size on its distribution was seen mainly as a change in the uniformity of penetration.
A quantitative chromatographic method for the determination of purity of oxytetracycline
Authors: Bailey F
Published: April 2011

A chromatographic method for the determination of oxytetracycline is described, employing a hexane-ethyl acetate-pH 3·3 buffer partition system supported on Celite. Chromatographic separation is followed by measuring the absorbance of the eluate at 263 nm. The system enables the determination of oxytetracycline to be made in the presence of anhydro-oxytetracycline, chlortetracycline, α- and β-apo-oxytetracycline, and epi-oxytetracycline, the last three being the most likely contaminants of crude material.
The use of a thermoelectric osmometer to measure the osmotic coefficients of aqueous solutions of sodium salicylate at 25°
Authors: Deshmukh A , Fleming R
Published: April 2011

The use of a thermoelectric osmometer to measure osmotic coefficients for the binary system water-sodium salicylate at low concentrations (0·0 to 0·3 molal) is described. The accuracy and reproducibility of the instrument have been enhanced by employing a microscope to measure sample and reference drop sizes. Activity coefficients, calculated from the osmotic coefficients obtained in these experiments, have been combined with density and diffusional measurements to calculate frictional coefficients for the system.
Dissolution and absorption of ICI 49,455
Authors: Flanagan T H , Broad R D , Rubinstein M H , Longworth A R
Published: April 2011

The dissolution rate of ICI 49,455 (1-isopropyl-1,2,3,4-tetrahydro-β-carboline) from tablet and capsule formulations cannot be related to in vivo absorption in dogs. The rate of partitioning of the drug into organic solvents and its absorption in goldfish and through human buccal membrane depend on the pH of the solution. Absorption increases with decrease in the degree of ionization. The dissociation constant and the elimination rate of the drug in man are such that high blood levels after oral administration are unlikely to occur.
The influence of stereochemistry on pKa, rate of quaternization and partition coefficients of corynantheidine-type alkaloids
Authors: Beckett A H , Dwuma-Badu D
Published: April 2011

In alkaloids of the corynantheidine group, the rate of quaternization at N-4 and the pKa values give a measure of the degree of steric hindrance at this site due to the axial hydrogen at C-3 and the ethyl group at C-20. These hinder the availability of the lone pair of electrons on N-4 to electrophiles. Partition coefficients indicate that lipid solubility is associated with planarity of the molecules; this explains why the more planar isomers (allo and normal) are more highly metabolized in microsomes than the less planar isomers (pseudo and epiallo).
The preparation and pharmacological properties of ψ-corbasil
Authors: Farrugia M T , Hunter W H , Kirk G
Published: April 2011

The synthesis is described of threo-α-methyl noradrenaline (ψ-corbasil). The assignments of the erythro and threo configurations to corbasil and ψ-corbasil respectively are supported by the evidence of the nmr spectra. Some preliminary results are reported for the relative pharmacological activity of the two isomers at α- and β-adrenergic receptors.
A new preparation of the isolated intact trachea of the guinea-pig
Authors: Farmer J B , Coleman R A
Published: April 2011

A preparation is described in which the guinea-pig isolated intact trachea is subjected to repeated transmural electrical stimulation with alternating square wave pulses. The intraluminal pressure is continuously sensed by a pressure transducer. An increase in the intraluminal pressure is the predominant response to electrical stimulation. This response is prevented by low concentrations of atropine. After the initial rise a small fall in intraluminal pressure occurs; this is prevented by low concentrations of propranolol. The sensitivity of the preparation to various drugs is described.
Effects of salicylate on the incorporation of orotic acid into nucleic acids of mouse tissues in vivo
Authors: Janakidevi K , Smith M J H
Published: April 2011

In mice, given intraperitoneal injections of orotic acid-5-3H, two peaks of incorporation of radioactivity at 30 min and 6 h occurred in the RNA of kidney and of liver and its subcellular components. The concurrent administration of salicylate, in doses of 200 mg/kg body weight and above, significantly inhibited the incorporation of the labelled orotic acid at 30 min but not at 6 h.
Pharmacological screening of some Brazilian plants
Authors: Barros Glauce S G , Matos F J A , Vieira J E V , Sousa Mirian P , Medeiros Mary C
Published: April 2011

Forty-five species of plants from several botanical families growing in North East Brazil have been examined for toxicity on mice and small fishes, cat blood pressure and respiration, isolated toad heart and rectus abdominis muscle, guinea-pig ileum, rabbit duodenum and rat uterus. A high toxicity to mice and fishes was exhibited by aqueous (A) and ethanolic (B) extracts from Luffa operculata, Peschiera affinis, Pithecelobium multiflorum (gall) and Zizyphus joazeiro and by extract B from Pithecelobium multiflorum (stembark). Cardiorespiratory activity was shown by Annona squamosa, Byrsonima sericea, Crataeva tapia, Erythrina velutina, Fagara rhoifolia, Operculina macrocarpa, Perschiera affinis, Pithecelobium multiflorum, Spondias lutea and Zizyphus joazeiro. Extracts A and B from Operculina macrocarpa and Pithecelobium multiflorum, extract A from Luffa operculata and Zizyphus joazeiro and extract B from Crataeva tapia and Peschiera affinis promoted a contraction of the toad rectus abdominis muscle. Both extracts from Annona aquamosa and Fagara rhoifolia (leaf) provoked a spasmogenic effect on guineapig ileum and a spasmolytic one on rabbit duodenum. Extracts A and B from Pithecelobium multiflorum, Vitex gardneriana and Zizyphus joazeiro exhibited a spasmogenic activity on both preparations, while extracts A and B from Peschiera affinis and extract B from Erythrina velutina also evidenced a spasmolytic activity on both preparations. Oxytocic activity was shown by both extracts from Annona squamosa, Byrsonima sericea, Pithecelobium multiflorum and Vitex gardneriana.