bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of some antiparkinsonian drugs on catecholamine neurons
Authors: Farnebo Lars-Ove , Fuxe Kjell , Hamberger Bertil , Ljungdahl Håke
Published: April 2011

The inhibitory effect of some antiparkinsonian drugs on the accumulation of catecholamines into rat dopamine and noradrenaline neurons was studied with isotope and histochemical fluorescence methods in vivo and in vitro. Benztropine was the most potent drug hitherto tested to inhibit accumulation of catecholamines into dopamine neurons and was effective down to a dose of 10mg/kg. Also ethybenztropine, brompheniramine, diphenylpyraline, chlorpheniramine and methixene, in doses of 50 mg/kg, inhibited accumulation of catecholamines. Atropine, scopolamine, benzhexol, diphenhydramine and many other antiparkinsonian agents were ineffective.
A new dry extract of cascara (Rhamnus purshiana D.C. bark)
Authors: Fairbairn J W , Simic S
Published: April 2011

The B.P. method of preparing a dry extract of cascara leads to significant breakdown of O-glycoside links in the active compounds. This is shown to be due to enzyme activity during percolation. A dry extract, containing most of the active glycosides originally present in the bark with no change in glycosylation status, can be prepared using boiling water as extracting solvent. A modification of the chemical assay process is recommended as well as the use of an official standardized extract with upper and lower limits for glycoside content.
Some effects of experimentally-produced cigarette smoke on the growth, vitamin C metabolism and organ weights of guinea-pigs
Authors: Hughes R E , Jones P R , Nicholas P
Published: April 2011

Guinea-pigs receiving a controlled dietary intake of L-xyloascorbic acid (ascorbic acid, vitamin C) inhaled experimentally produced cigarette smoke for periods of up to 20 min each day. Growth rate was significantly depressed by the smoke treatment, an effect at least in part attributable to a reduction in food intake. Growth of individual organs was not depressed to the same extent as that of the body as a whole. The lungs of the animals receiving smoke were significantly heavier than those of control animals (P < 0·05). The concentration of ascorbic acid in the adrenal glands was significantly lower in the animals receiving smoke than in the controls (P < 0·01). The smoke-induced depression of the adrenal gland ascorbic acid was apparent after 4 days; after 18 days marked adrenal hypertrophy accompanied the lowered ascorbic acid levels.
Combined gas-liquid chromatography—mass spectrometry in the study of barbiturate metabolism
Authors: Gilbert J N T , Millard B J , Powell J W
Published: April 2011

Combined gas-liquid chromatography-mass spectrometry is shown to be a useful technique for the identification of barbiturates and their metabolites, when applied to NN’-dimethyl derivatives.
Plasma protein binding of chlorpromazine
Authors: Curry Stephen H
Published: April 2011

More than 90% of the plasma content of chlorpromazine over a concentration range from 0·008 to 15·1 μg/ml was bound to human plasma protein. Binding was affected by the pH of the aqueous medium; with few exceptions the higher values were obtained at the higher pH values. Binding was highest in some of the plasma samples from humans, and successively lower in plasma from dogs, rabbits and rats. Binding of chlorpromazine after administration of the drug to psychiatric patients, and after in vitro addition of the drug to plasma, was reversible. Variation in binding in plasma from different humans was marked; the amount bound varied from 91·0 to 99·0%. Thus the variation in the amount free was from 1·0–9·0%.
A note on the determination of dichlorophen and hexachlorophene in mixtures
Authors: Daisley R W , Olliff C J
Published: April 2011

Dichlorophen and hexachlorophene can be separated and estimated rapidly. Separation was achieved on thin-layer chromatograms using ethyl acetate containing 10% v/v of methanol and silica gel, the appropriate areas for each compound being collected and eluted with methanol. The absorbances of these solutions at 286 and 299 nm respectively were measured and compared with standard curves. Application of the method to several commercial formulations was successful.
The use of boronate derivatives in the characterization of catecholamines and related β-hydroxy-amines by gas liquid chromatography-mass spectrometry
Authors: Anthony G M , Brooks C J W , Middleditch B S
Published: April 2011

The gas chromatographic separation of various β-hydroxy-amines in the form of derived 1, 3, 2-oxazaborolidines is complemented by a mass-spectrometric study of cyclic boronates of natural catecholamines. These derivatives and their synthetic analogues yield characteristic mass spectra. Closely similar compounds, such as the n-butylboronates of the diastereoisomers (—)-ephedrine and (+)-ψ-ephedrine, give almost identical spectra but can be readily distinguished by their glc retention times. The same can be said for the positional isomer pairs synephrine and phenylephrine, and for octopamine and 4-deoxynoradrenaline. Mass-spectrometric fragmentation modes are postulated from a comparison of the shifts in the masses of fragment ions corresponding to various substituents in the group of biological amines studied. Additional correlations are derived from studies of methyl-, cyclohexyl- and phenyl-boronates.
1, 2-Disubstituted cyclohexanes as substrates of acetylcholinesterase and muscarinic agents. A re-investigation
Authors: Kay J B , Robinson J B , Cox B , Polkonjak D
Published: April 2011

The previously reported high rates of acetylcholinesterase-catalysed hydrolysis of (±)-cis- and (±)-trans-2-dimethylaminocyclohexyl acetate methiodide (Baldridge, McCarville & Friess, 1955) have been re-investigated, the enantiomers of each geometrical isomer being used. The cis-enantiomers were inactive as substrates and the trans-enantiomers were hydrolysed at a very slow rate. These results are confirmed by studies on muscarinic tissue (guinea-pig ileum) in which only a weak stimulatory response was given with the trans-enantiomers (the cis-enantiomers were inactive). With each of the test systems used, the acetylcholine receptor showed an inversion of the “normal” configurational specificity although the enantiomer potency ratio was small, a phenomenon which has been observed in previous reports of inversion of configurational specificity.
Stereochemical influences upon antihistamine activity. Further studies of isomeric 4-amino-1, 2-diarylbutenes
Authors: Casy A F , Ison R R
Published: April 2011

The acid-catalysed dehydration of some 4-amino-1, 2-diarylbutan-2-ols yields all four possible 4-amino-1, 2-diarylbutenes. The structure and configuration of pure isomers have been established from spectroscopic data, and the ability of these compounds to anatagonize histamine-induced contractions of the guinea-pig ileum is reported. The most potent derivatives are all cis(H/Ar)-4-amino-1, 2-diarylbut-2-enes. These results together with other data are discussed in terms of the possible structural and conformational requirements of histamine antagonists.
A comparison of the local anaesthetic-, “quinidine-like”- and adrenergic β-blocking-activities of five β-receptor antagonists
Authors: Davis W G
Published: April 2011

Propranolol, pronethalol, INPEA, MJ1999 and MJ1998 exhibit local anaesthetic activity when assessed by infiltration anaesthesia and at motor nerve endings but only propranolol, pronethalol and INPEA exhibit local anaesthetic activity on the phrenic motor nerve. All the β-adrenergic blocking agents exhibit a “quinidine-like” activity and there appears to be a close correlation between local anaesthetic and “quinidine-like” activities, which cannot be extended to include adrenergic β-receptor antagonism.
The effect of isoniazid and some anticonvulsant drugs on the γ-aminobutyric acid content of mouse brain in insulin hypoglycaemia
Authors: Saad Samir Fahmy
Published: April 2011

Phenobarbitone, prominal and primidone protect mice from insulin convulsions and raise their lowered cerebral hemisphere GABA content. Phenobarbitone and primidone are superior to prominal and produce a significant increase in the insulin depleted GABA content. Isoniazid potentiates insulin convulsions and significantly lowers the insulin depleted GABA content. It is probable that insulin depletion of cerebral hemisphere GABA content is a rationale of hypolgycaemic convulsions.
The transfer and penetration of fatty alcohols and fatty acids in relation to their self-bodying action in emulsions
Authors: Talman F A J , Rowan E M
Published: April 2011

The transfer of fatty alcohols and acids from an oil phase to an aqueous solution of surfactant has been examined. Also, penetration of the solid amphiphile by these surface-active agents has been observed by optical microscopy. The findings have been correlated with the flow behaviour of emulsions and gels containing these materials. The results indicate that before a fatty alcohol or acid, in conjunction with a surfactant, will have any self-bodying action in an emulsion two conditions must be fulfilled. Firstly, a portion of the alcohol or acid must migrate from the oil to the aqueous phase and secondly, the surfactant molecules must be of such size or shape or present in sufficient concentration to permit penetration of the amphiphile crystal lattice and the formation of a ternary liquid crystalline phase.
An in vitro model for drug absorption studies
Authors: Robertson J S , Bode O
Published: April 2011

The transfer of salicylic acid and of three sulphonamides from an aqueous phase of pH 2 or pH 5 through an intervening organic phase to an aqueous phase of pH 7.4 has been studied using a rotating cell. The manner of operation of the cell promotes rapid drug transfer without vortexing or emulsification of the phases. The rates of transfer of the drugs showed the anticipated pH dependance.
Some observations on the ageing of sodium chloride compacts
Authors: Rees J E , Shotton E
Published: April 2011

The diametrical crushing strength of an ideal system of compacted particulate material, and the relation between strength and mean compaction pressure depend on the time at which the strength is determined. Strength increases of over 100% during the first hour after compression are attributed to stress relief of the sodium chloride crystals and interparticulate bonds. The effects of elevated temperature, and also humidity, on the strength and physical structure of compacts are evaluated. Relaxation behaviour of compacts containing light liquid paraffin is also investigated.
Some problems encountered in attempting to estimate catecholamine turnover using labelled tyrosine
Authors: Persson T , Waldeck B
Published: April 2011

Rats were given [3H]tyrosine intravenously. The decrease of [3H]noradrenaline (3H-NA) and [3H]dopamine (3H-DA) from 2 to 6 h after the [3H]tyrosine injection was estimated in the cerebral cortex, brain stem, caudate nucleus, spinal cord and adrenal medulla. Half-lives were estimated with or without the tyrosine hydroxylase inhibitor H 44/68 or the dopamine-β-hydroxylase inhibitor FLA-63, given 2 h after the [3H]tyrosine. The influence of the inhibitors on endogenous noradrenaline was also studied. H 44/68 did not change the half-life of 3H-NA in the central nervous system but FLA-63 reduced it considerably. FLA-63 reduced endogenous noradrenaline more than did H 44/68. The mechanism responsible for the faster turnover of noradrenaline after FLA-63 has not yet been elucidated. In the adrenal medulla the [3H]adrenaline + 3H-NA level rose significantly from 2 to 6 h after the injection of [3H]tyrosine. The synthesis inhibitors prevented this rise, indicating that appreciable amounts of labelled precursors remain for a long time after the injection of the labelled tyrosine. Some problems encountered with the different methods for turnover determinations are discussed on the basis of these data.
Nuclear magnetic resonance spectroscopy of the trimethylsilyl ethers of some hydroxyphenylalkylamines
Authors: Forrest Janet E , Heacock R A , Forrest T P
Published: April 2011

A number of hydroxyphenylalkylamines have been converted into their trimethylsilyl ethers by the action of hexamethyldisilazane in pyridine. The derivatives are completely soluble in carbon tetrachloride and these solutions are suitable for nuclear magnetic resonance spectroscopy. The nmr spectra of 16 potentially biologically active phenylalkylamines have been obtained in this way. The spectral data are presented and the significance of the results discussed.
Reduction of gastric acid secretion and ulcer formation by 3,3-dimethyl-1-(3-methylaminopropyl)-1-phenylphthalan (Lu 3–010); an inhibitor of noradrenaline uptake
Authors: Lippmann W
Published: April 2011

Lu 3–010 [3,3-dimethyl-1-(3-methylaminopropyl)-1-phenylphthalan], administered intraperitoneally, blocks the uptake of [3H]noradrenaline into the mouse and rat heart and has an activity 5 times greater than imipramine and comparable to that of desipramine. Lu 3–010 inhibits basal gastric acid secretion in the rat and is 4 and 2 times more potent than imipramine and desipramine, respectively. The drug is about 9 times more potent than desipramine in preventing the pentagastrin-induced stimulation of gastric acid secretion in the rat. Lu 3–010 reduces the incidence of stress-induced gastric lesions in the rat, exhibiting an ED50 ± s.e. of 6.3 ± 1.4 mg/kg, and at 10 mg/kg, ulcer development in the 17-hour Shay test is reduced by 50%.
The identification, isolation, and preservation of Δ9-tetrahydrocannabinol (Δ9-THC),
Authors: TURK ROBERT F , MANNO JOSEPH E , JAIN NARESH C , FORNEY ROBERT B
Published: April 2011

(—)-trans-Δ9-Tetrahydrocannabinol (Δ9-THC) was isolated from marihuana plant extract, by adsorptive column and glc. The adsorptive column chromatography method consisted of chromatographing marihuana extract on a column packed with a mixture of silica gel (gas chromatography grade (100/120 mesh), silver nitrate and calcium sulphate (CaSO4·H2O) (3:1:0·5) with benzene as the eluting solvent. The glc method consisted of chromatographing the extract on a 3 ft silanized glass column (3/8 inch o.d.) packed with 1·5 ft of 2% QF-1 and 1·5 ft of 2% OV-17 on chromosorb W, AW 30–60 mesh, prep grade. A purity of 99% for the isolated Δ9-THC was confirmed by infrared spectroscopy, nuclear magnetic resonance, mass spectroscopy. The effects of storage conditions on Δ9-THC stability, monitored by glc, indicated the best method for preserving Δ9-THC was at 0°, protected from light, stored under nitrogen.
The spontaneous electrical and mechanical activity of the longitudinal smooth muscle of the rabbit duodenum and its modification by drugs and temperature changes
Authors: SMALL R C , WESTON A H
Published: April 2011

The electrical and mechanical activity of strips of longitudinal smooth muscle from the rabbit duodenum was recorded using the sucrose gap method. The muscle exhibited rhythmic tension changes each of which was associated with a slow potential wave of electric depolarization surmounted by a burst of spike activity (a multispike complex). Cooling the tissue reduced the frequency of tension waves and multispike complexes. Catecholamines produced a reduction in the amplitude of tension waves. This was associated with hyperpolarization and decreased spike activity. Slow wave frequency and amplitude were unaffected. Acetylcholine, methacholine and histamine produced tension wave fusion associated with depolarization and increased spike activity.
dl-5-Hydroxytryptophan-induced changes in central monoamine neurons after peripheral decarboxylase inhibition
Authors: FUXE KJELL , BUTCHER LARRY L , ENGEL JÖRGEN
Published: April 2011

The histochemical effects of 500 and 1000 mg/kg of dl-5-hydroxy-tryptophan (5-HTP), both alone and in combination with a peripheral decarboxylase inhibitor (seryl-trihydroxy benzyl hydrazine; Ro 4–4602) have been examined on central monoamine neurons of rats by the Falck-Hillarp fluorescence technique that demonstrates monoamines and their precursors. 5-HTP alone or together with Ro 4–4602 caused only weak intraneuronal accumulation of 5-HT in the central 5-HT neurons, in spite of an increased entry of 5-HTP into the brain after Ro 4–4602 treatment, as shown by an increase in the specific neuropil fluorescence and a reduction of 5-HT accumulation in the cells of the capillary walls. Ro 4–4602 markedly potentiated the effects of 5-HTP on the central dopamine neurons, many of which became clearly yellow fluorescent. The mechanism of dopamine depletion by 5-HTP is probably therefore mainly one of displacement. The effects on the noradrenaline neurons were also potentiated by Ro 4–4602 pretreatment, the neurons exhibiting a yellow-green fluorescence. This depletion may therefore also be mainly be due to amine displacement. It is concluded that the ability of the 5-HT neurons to take up and accumulate 5-HT in the presence of 5-HTP is relatively low in spite of large amounts of 5-HTP present in the brain neuropil after extracerebral decarboxylase inhibition.
Spasmolytic action of adenosine on the guinea-pig ileum
Authors: SEHORN S L , BOROWITZ J L
Published: April 2011

Adenosine (10−5M) reduces the contractile response of the guinea-pig isolated ileum to 5-hydroxytryptamine or barium more than the responses to acetylcholine or histamine. Adenosine also inhibits the contractile response of the guinea-pig ileum to a calcium-free medium. These results suggest that adenosine effects a blockade of the indirect responses to barium or 5-hydroxytryptamine mediated through intrinsic nerves and has a weak direct inhibitory effect on the smooth muscle cells of this tissue.
A comparison of granules prepared by pan granulation and by massing and screening
Authors: GANDERTON D , HUNTER B M
Published: April 2011

Granules of lactose and calcium phosphate were prepared by pan granulation and by massing and screening. Capillary forces and the gentle action of tumbling in the pan were inadequate to compact the fine cohesive calcium phosphate but were highly effective with the less cohesive lactose where the absence of shear gave very high densification. Whereas massing and screening provided the necessary forces for consolidating calcium phosphate, with lactose a more open structure resulted which further dilated during screening. Increase in both moisture content and time of mixing increased granule density but the degree varied with both method and material as did granule shape, strength and compressibility.
Solute migration during granule drying
Authors: RIDGWAY K , RUBINSTEIN M H
Published: April 2011

Spherical granules of magnesium carbonate, 12 mm diameter, have been dried under controlled conditions in a drying tunnel at 44°, the rate of moisture loss being continuously recorded. The granulating agent was polyvinylpyrrolidone (PVP). Granules were removed at various times for analysis. By controlled attrition, successive layers of powder were removed from the granules. The powder was analysed for PVP by infrared spectroscopy, and the friability, modulus of elasticity and Brinell hardness of the granules were measured as a function of depth from the granule surface. The radial distribution of the PVP and its physical effect on the granule properties were thus found.
A new buccal absorption model
Authors: DEARDEN J C , TOMLINSON ERIC
Published: April 2011

Buccal absorption tests indicate that loss of drug from the oral cavity cannot be accounted for solely in terms of passive diffusion into the buccal membrane. A model involving protein-binding is proposed, which satisfactorily explains the observed loss. Studies on two different physical simulations of buccal absorption confirm that the proposed model is consistent with the in vivo results.
The dissolution times of spherical particles
Authors: RIDGWAY K , PEACOCK D G
Published: April 2011

The differential equation governing the rate of change of radius of a spherical particle dissolving or growing in a fluid has been numerically integrated by computer. The particle radius, as a function of time, can thus be calculated, and the dependence of the overall particle lifetime upon physical parameters obtained. The effects of high mass flux, change of solubility with particle size, and progressive saturation due to dissolution into a finite volume of liquid can all be taken into account during the integration process. Results are presented for salicylic, boric and citric acids dissolving in and crystallizing from water; these represent the behaviour of sparingly soluble, moderately soluble and very soluble compounds respectively.
The determination of residual ethylene oxide and halogenated hydrocarbon propellants in sterilized plastics
Authors: WARREN B
Published: April 2011

A specific and sensitive method is described for the determination of residual ethylene oxide, dichlorodifluoromethane and trichlorofluoromethane in sterilized plastic surgical equipment. Residues are isolated from the plastics by high vacuum distillation and analysed by gas chromatography using an exponential dilution apparatus, to avoid the use of solvents. Under the conditions specified, a lower limit of 1 ppm of each component could be detected in blood giving sets of which the main plastics material was PVC. The rate of loss of each component has been studied, to indicate the necessary holding time of the material before it can be considered safe to use.
A polarographic method for the determination of flurandrenolone
Authors: HEASMAN M J , WOOD (IN PART) A J
Published: April 2011

A simple fast scan polarographic method has been developed for the determination of the Δ4-3 ketosteroid flurandrenolone in pharmaceutical formulations. The polarographic peak current due to steroid reduction is measured after ointments have been subjected to a preliminary extraction procedure and creams have been treated with tannic acid to precipitate interfering excipients. The method enables concentrations down to 0·01 % w/w of the steroid to be measured. Neomycin sulphate does not interfere and clioquinol is readily removed using an ion exchange resin. Evidence is presented to show that the carbon-fluorine bond rather than the enone is primarily reduced. The method is faster than a colorimetric method using tetrazolium blue and has a similar accuracy and precision.
Some bronchoconstricting and bronchodilating responses of human isolated bronchi: Evidence for the existence of α-adrenoceptors
Authors: MATHÉ A A , ÅSTRÖM A , PERSSON N-Å
Published: April 2011

Isolated strips of human bronchi obtained during thoracic surgery exhibited pharmacological responses very similar to those of other species (e.g. guinea-pig). Analysis of the action of some sympathomimetic amines indicated that the human bronchi also possess a sparse population of α-adrenoceptors. Propranolol (>1 μg/ml) had a direct bronchoconstricting action, whereas another β-adrenoceptor blocking agent, alprenolol, produced bronchodilatation. Phentolamine (>4 μg/ml) also produced a bronchodilatation of its own. Theophylline and dibutyryl cyclic AMP produced dose-dependent relaxations. The strips were effectively contracted by acetylcholine, histamine, prostaglandin F2α (PGF2α), slow reacting substance (SRS) and bradykinin. Bradykinin, regardless of the dose, produced bronchoconstriction in some preparations and dilatation in others. 5-Hydroxytryptamine produced bronchodilatation but at very high concentrations a constriction was obtained.
The reversal of phenoxybenzamine-produced α-adrenoceptor blockade by the isomers of propranolol and INPEA
Authors: DAVIS W G
Published: April 2011

Isomers of propranolol and N-isopropyl-p-nitrophenylethanolamine (INPEA) were used to demonstrate that there are two mechanisms by which the β-adrenoceptor blocking agents will reverse phenoxy-benzamine-produced α-adrenoceptor blockade. In the seminal vesicle preparation, prior administration of either isomer initially protected the receptors from phenoxybenzamine blockade when the contact time for phenoxybenzamine was short. The isomers were equi-effective, suggesting that this action is independent of β-adrenoceptor blocking activity. When the contact time of phenoxybenzamine was prolonged, the ability of the isomers to protect the α-receptors was lost. In the rat blood pressure preparation, after the development of phenoxybenzamine-produced α-adrenoceptor blockade, (-)- and (±)-propranolol or (-)- and (±)-INPEA, in doses that produced marked β-adrenoceptor blocking activity, partially reversed the α-adrenoceptor blockade. Identical doses of (+)-propranolol or (+)-INPEA, which exhibited weak β-adrenoceptor blocking activity did not produce any reversal. The reversal of phenoxybenzamine-produced α-adrenoceptor blockade in this situation appears therefore to be dependent upon the development of β-adrenoceptor blockade.
The binding of bupivacaine to maternal and foetal plasma proteins
Authors: MATHER L E , LONG G J , THOMAS J
Published: April 2011

The binding of bupivacaine to maternal and foetal plasma proteins has been investigated using a three-compartment dialysis apparatus, in which maternal and foetal plasma could be examined simultaneously. Maternal protein bound approximately twice as much bupivacaine as foetal protein per gram of protein at drug concentrations in the range 0·05 to 5·0 μg/ml. Over the same range of concentrations, 92–78% of bupivacaine was bound to maternal plasma protein but only 35–31% was bound to human albumin indicating that other proteins are involved in the binding of the drug to plasma proteins.
The influence of the moisture content of the fibrous support of a nasal inhaler upon the concentration of drug in the air stream
Authors: ARMSTRONG P A M , CARLESS J E , ENEVER R P
Published: April 2011

The moisture contents of cellulose acetate and paper fibrous support materials used in nasal inhalers have been determined by infrared drying and extraction techniques. The mutual solubilities of water and methylamphetamine have been investigated at various temperatures, and the results indicated that the system exhibited both upper and lower consolute temperatures. The effect of molar composition of water on the total and partial vapour pressures of methylamphetamine-water mixtures have also been investigated. Positive deviations from Raoult's Law were observed for both total and partial pressures. The present results have been related to data obtained previously with an inhaler system to show that the moisture contents of the fibrous supports are partially responsible for the discrepancy between the derived and absolute vapour pressure values for methylamphetamine.
Synthesis and pharmacology of 1-(2-thioxopyrrolidino)-4-pyrrolidino-2-butyne, the thiolactam analogue of oxotremorine
Authors: LINDEKE B , KARLÉN B , DAHLBOM R , GREEN R , JENDEN D J
Published: April 2011

The thiolactam analogue of oxotremorine (I) has been prepared and examined for muscarinic activity in mice and on guinea-pig ileal preparations. It is inactive in itself, but is transformed in vivo to oxotremorine (II), which has been identified in the urine of mice. The urine also contains 1-(2-oxopyrrolidino)-4-pyrrolidino-2-butanone (III) which is formed non-enzymatically from I under acidic conditions, but does not display any acetylcholine-like properties in vivo or in vitro. Oxotremorine is not formed from I in vitro.
Pharmacodynamic effects of dehydroemetine
Authors: SALAKO L A
Published: April 2011

The pharmacodynamics of dehydroemetine were studied in isolated preparations and in whole animals. Dehydroemetine had no effect on the guinea-pig isolated ileum but non-specifically antagonized the spasmogenic effect of histamine, acetylcholine and nicotine on this tissue. Dehydroemetine in small concentrations inhibited relaxations of the guinea-pig and rabbit ileum produced by stimulating the sympathetic nerve without inhibiting the effect of noradrenaline. Twitches of the guinea-pig ileum elicited by transmural stimulation were blocked by dehydroemetine while higher doses of the drug also inhibited the indirectly elicited contractions of the isolated rat diaphragm. In vivo, neuromuscular blocking action could not be demonstrated for dehydroemetine while toxic doses were required to demonstrate the presence of an adrenergic neuron blocking action. Dehydroemetine had no anaesthetic action when applied locally to the rabbit cornea. Concentrations of the drug which caused local anaesthesia when injected intradermally into guinea-pigs also caused skin necrosis. It is concluded that dehydroemetine lacks any specific adrenergic neuron blocking action or neuromuscular blocking action or local anaesthetic action. It is suggested that the effects demonstrated are due to non-specific action at the nerve endings.
Effect of amphetamines on tryptophan concentrations in mice and rats
Authors: SCHUBERT JOHAN , SEDVALL GÖRAN
Published: April 2011

(±)-Amphetamine and some of its analogues were administered intraperitoneally to mice and rats and the concentrations of tryptophan in tissues were analysed by fluorimetric and microbiologic techniques. The concentration of tryptophan in brain was markedly increased by (±)-amphetamine and reached a maximum about 80 min after drug administration. The effect was dose-dependent with a threshold dose below 1 mg/kg. (+)-Amphetamine was significantly more potent than p-chloroamphetamine and p-hydroxyamphetamine, indicating that the changes in tryptophan concentrations might be related to the central stimulating effect of the drugs. (±)-Amphetamine delayed the disappearance from brain of intravenously administered [3H]tryptophan. Inhibition of monoamine oxidase by nialamide (100 mg/kg) and tryptophan hydroxylase by H 22/54 (500 mg/kg) had no effect on the tryptophan concentration in brain.
The interaction of some oral contraceptive steroids with lipid monolayers and with erythrocytes
Authors: FLORENCE A T , RAHMAN R
Published: April 2011

Some steroids used in oral contraceptive combinations have been found to interact with cholesterol and lecithin spread as monolayers on water and to protect erythrocytes against haemolysis. No simple relation between steroid structure and these interactions was found, although in general the more water-soluble members of a group of structurally related compounds interacted to a lesser extent. No distinction could be observed in the behaviour of progestogens and oestrogens in the systems studied. It is suggested in the light of the evidence presented here and from data in the literature that these steroids may adsorb at lipid surfaces and may penetrate lipid membranes. This gives substance to the hypothesis that some steroids adsorb at platelet surfaces and alter the surface properties or the permeability of the platelet membrane sufficiently to cause increased platelet aggregation.
The effect of chlorthalidone on blood sugar and glucose tolerance in the rat
Authors: FURMAN B L , Boswell J
Published: April 2011

Chlorthalidone, in high doses, failed significantly to influence blood sugar or intravenous glucose tolerance in the rat, following the intraperitoneal injection of single doses or 28 day oral treatment with the drug (100 mg/kg daily). The significant effect of the drug in stimulating glucose transfer in everted sacs prepared from rat intestine may explain the trend towards altered oral glucose tolerance observed. Chlorthalidone failed significantly to influence the blood sugar of alloxan diabetic rats and did not modify glucose uptake by rat-hemidiaphragm muscle or epididymal adipose tissue incubated in vitro in the presence or absence of insulin.
The effects of corticosteroids on the reduction of α-adrenoceptor blockade produced by β-adrenoceptor blocking agents
Authors: DAVIS W G , BOURNE R K
Published: April 2011

The inhibition of the pressor effects of noradrenaline by phenoxybenzamine was reduced by propranolol and sotalol in the normal and acutely adrenalectomized, but not in the chronically adrenalectomized, rat. The administration of a glucocorticoid, but not a mineralocorticoid, to the chronically adrenalectomized rat, produced a preparation in which the phenoxybenzamine-produced α-adrenoceptor blockade was reduced by the β-adrenoceptor blocking agents, demonstrating that this action is glucocorticoid-dependent.
The uptake by Escherichia coli and growth inhibitory properties of benzyl alcohol and phenethyl alcohol
Authors: LANG MILDRED , RYE R M
Published: April 2011

The effects of benzyl alcohol (0–4 mg/ml) and phenethyl alcohol (0–2.5 mg/ml) on the rate of mass increase in cultures of E. coli were studied by absorbance measurements. Growth rate constants in the partially inhibited cultures were calculated. With both agents the growth rate was reduced on increasing the alcohol concentration, the extent of this reduction becoming progressively larger for equal increments in concentration. The inhibition of growth was shown to be reversible and to result from a uniform inhibition of the individual cells. The overall cellular uptake of benzyl alcohol was approximately the same as that of phenethyl alcohol. With both agents the uptake was proportional to the concentration of alcohol remaining in the medium and was independent of contact time within the range of 10–90 min. Phenethyl alcohol is, however, more effective than benzyl alcohol in inhibiting growth. This is attributed to a greater uptake of the former by the cellular membrane.
The sterols and tetracyclic triterpenoids of Digitalis purpurea L. seeds
Authors: EVANS F J
Published: April 2011

Three types of sterols were isolated from the non-saponified fraction of D. purpurea seed oil. These were the 4,4′-dimethylsterols, the 4α-methylsterols and the 4-desmethylsterols. By combination of t.l.c., g.l.c. and mass spectrometry, the first group were found to consist of cycloartenol and 24-methylenecycloartenol, the second group of 24-methyl-lophenol, 24-ethyl-lophenol, 24-methylenelophenol, 24-ethylidenelophenol, obtusifoliol, 4α-methylzymosterol and cycloeucalenol. The third group of true phytosterols consisted of cholesterol, campesterol, stigmasterol, β-sitosterol, fucosterol, 28-isofucosterol and 24-methylenecholesterol. Possibly present also in this group were 7-ene-cholestenol, 7-ene-campestenol, 7-ene-22-dihydrostigmastenol, 7-ene-24-methylenecholestenol and 7-ene-isofucostenol.
Enhanced migration of the ionized forms of acidic drugs from water into chloroform in the presence of phospholipids
Authors: FURUSAWA SHUNJI , OKUMURA KATSUHIKO , SEZAKI HITOSHI
Published: April 2011

The transfer process of various acidic drugs from water into chloroform containing phospholipids has been examined using a nonemulsifying system. The ionized forms of the drugs which have little lipid solubility show a marked increase in transfer to the chloroform phase containing lecithin at the physiological pH of the small intestine. The pH-profiles of salicylic acid, p-aminobenzoic acid and sulphisoxazole transfer are in good agreement with available in situ absorption data. These results suggest a role for phospholipids in the intestinal absorption of ionized acidic drugs which has not been clearly apparent with pH-partition hypothesis alone.
The effects of apomorphine, (+)-amphetamine and l-dopa on maximal electroshock convulsions—a comparative study in the rat and mouse
Authors: MCKENZIE G M , SOROKO F E
Published: April 2011

The anticonvulsant activity of apomorphine, (+)-amphetamine and pargyline + l-dopa was examined in the rat and mouse. Whereas all three treatments produced anticonvulsant effects in the rat, only (+)-amphetamine and l-dopa were anticonvulsant in the mouse. It is suggested that enhanced dopamine-like activity is responsible for the anticonvulsant activity of these three drugs in the rat. The anticonvulsant activity of (+)-amphetamine and l-dopa in the mouse may be unrelated to their pharmacological activity on dopaminergic neurons.
Hypothermic effect of apomorphine in the mouse
Authors: FUXE K , SJÖQVIST F
Published: April 2011

A new effect of apomorphine in lowering body temperature in mice is presented. The hypothermic effect is antagonized by haloperidol and pimozide, which block dopamine receptors in brain, and by desipramine and protriptyline which preferentially inhibit amine uptake in noradrenaline neurons. The finding may indicate that dopaminergic mechanisms are involved in temperature control in mice.
Determination of yield value of hectorite gels by the falling sphere method
Authors: CARLESS J E , OCRAN J
Published: April 2011

Two variations of the falling sphere method were used to measure the static yield values of aqueous dispersions of a synthetic hectorite and the results compared with those obtained using the Ferranti Shirley cone-plate viscometer. Yield values were calculated from three equations proposed by various workers but only one equation gave results in reasonable agreement with the cone-plate viscometer. Advantages of the falling sphere method and the derivation of the equations are discussed.
Some parameters describing the dissolution rate of salicylic acid at controlled pH
Authors: COLLETT J H , REES JUDITH A , DICKINSON N A
Published: April 2011

Rates of dissolution of salicylic acid have been determined at constant pH in the absence of buffer salts by use of a pH-stat. The dissolution rate increased with increasing pH up to a maximum of pH 4·0. An increase in stirring speed brought about an increase in dissolution rates at each pH. Diffusion layer thickness and diffusion coefficients have been determined utilizing viscosity and density measurements.
Sound-withdrawal hypertension in rats—a new form of experimental hypertension
Authors: Marwood J F , Lockett Mary F
Published: April 2011

Females of an inbred strain of Wistar rats, initially 160–180 g, develop hypertension when transferred from the stock (normal rat) room (NRR) to a sound-proofed semi-anechoic room (SPR). No hypertension develops when sounds in the NRR are relayed unchanged into the SPR. The hypertension reaches maximum at 4 weeks then decreases slightly to stabilize at a level approximately 30 mm Hg above normal before, and 20 mm Hg above normal after, pentolinium blockade. Histological changes are demonstrable in small arteries after 12 weeks in the SPR. Augmented pressor responses to fixed doses of noradrenaline and of tyramine, but not of angiotensin II and of vasopressin, and a general increase in organ/body wt ratios were evident in weeks 3–5 after entry to the SPR, but had reversed by week 12. These findings contrast with those made on salt-DOCA hypertensives.
Interactions between oxotremorine and inhibitors of Cholinesterase enzymes
Authors: Cox B , Tha S J
Published: April 2011

Interactions between oxotremorine and physostigmine or dyflos have been investigated in mice using doses giving approximately 50% inhibition of mouse brain cholinesterase. Oxotremorine LD50 was unaffected by pretreatment of mice with the anticholinesterases. Its ED50 (tremor) was decreased by physostigmine and neostigmine but not by dyflos. Dyflos antagonized oxotremorine hypothermia, physostigmine was without effect. Oxotremorine did not alter the inhibitory activity of the anticholinesterases. The lack of potentiation of oxotremorine by cholinesterase inhibitors suggests it acts directly in these tests by a mechanism independent of its ability to increase tissue acetylcholine concentration.
Alkaloids from the seeds of Strychnos wallichiana Steud. ex DC. (Strychnos cinnamomifolia Thwaites var. wightii A. W. Hill)
Authors: Bisset N G , Phillipson J D
Published: April 2011

The seeds of a south Indian sample of Strychnos wallichiana Steud. ex DC., previously analysed by Short (1924) under the name S. cinnamomifolia Thwaites and thought to contain mostly brucine with a little strychnine, have now been shown to contain a new base 4-hydroxy-3-methoxystrychnine (I) as the major alkaloidal constituent. Smaller amounts of strychnine, 4-hydroxystrychnine, brucine, vomicine, 4-hydroxy-3-methoxy-N-methyl-sec.-pseudostrychnine (II), and nova-cine and possibly also α-colubrine are present.
The tautomer ratio of histamine
Authors: Ganellin C R
Published: April 2011

The tautomeric equilibrium constant Kt for the two tautomeric forms (Nτ-H and Nπ-H) of histamine mono-cation is determined from the difference between the pKa values of Nπ- and Nτ-methylhistamines, and of Nπ- and Nτ-benzylhistamines. The ratio of concentrations of tautomers [Nτ-H]/[Nπ-H] = Kt is 4ṁ2 indicating that the histamine mono-cation exists in aqueous solution approximately 80% as the Nτ-H-tautomer and 20% as the Nπ-H tautomer. From the value of Kt and pKa1 of histamine the individual ionization constants at 25° of the two tautomers are derived. Tautomer Nτ-H (pKa1 6ṁ16) is a slightly weaker base than is tautomer Nπ-H (pKa1 6ṁ79).
The effect of carbenicillin on the haemostatic mechanism
Authors: Lederer D A , Davies T , Connell G , Davies J A , McNicol G P
Published: April 2011

Carbenicillin has no effect on the thrombin time, partial thromboplastin time, prothrombin time, platelet factor 3 availability, fibrinogen and plasminogen levels, Factor XIII, fibrin plate lysis or euglobulin lysis time in vitro in concentrations from 20–1280 μg ml−1. After incubation with plasma, carbenicillin inhibited platelet aggregation to ADP at all the concentrations examined (20–1280 μg ml−1). The same coagulation tests were unaffected 30 min and 4 h after intravenous administration of 5 g of carbenicillin to six normal subjects, though some impairment of platelet response to ADP occurred in three subjects. This impairment of platelet function is considered unlikely to contribute towards a bleeding tendency in normal subjects but might perhaps be a contributory factor in haemostatic failures in patients with uraemia.
The distribution of Δ1-tetrahydrocannabinol and 7-hydroxy-Δ1-tetrahydrocannabinol in the mouse brain after intraventricular injection
Authors: Gill E W , Lawrence D K
Published: April 2011

Δ1-Tetrahydrocannabinol (Δ1-THC) and 7-hydroxy-Δ1-THC were injected into the cerebral ventricles of mice by an improved technique, and the potencies of the drugs were measured by the mouse catalepsy test. Both drugs were found to have the same activity when administered by this route as after intravenous injection. Autoradiographic experiments with tritium-labelled compounds showed that at the time of the peak behavioural effect almost all the injected dose of 3H-Δ1-THC (1.6 mg kg−1) or 3H-7-hydroxy-Δ1-THC (0.6 mg kg−1) remained in the intraventricular space and had not penetrated the brain tissue. Δ1-THC was found to remain in the ventricles after the behavioural effect had disappeared; 3% of the injected dose was still present 2 days after injection of 3H-Δ1-THC (1.6 mg kg−1).
The transfer of salicylic acid across a Cellophane membrane from micellar solutions of polysorbates 20 and 80
Authors: Withington R , Collett J H
Published: April 2011

In the pH range 1 to 5 there is a linear relation between the rate constant for salicylic acid transfer across a cellophane membrane and the fraction of ionized drug present at each pH. The rate constant for ionized molecules is about 60% of that for unionized molecules. The presence of polysorbates 20 and 80 in the drug solution markedly decreases the apparent transfer rate constant of salicylic acid at low pH. When transfer rate constants obtained in the presence of surfactant are calculated in terms of the non-micellar concentration of salicylic acid they compare favourably with those obtained in the absence of surfactant. These results indicate that micellar drug does not participate in the transfer process.
Serum and blood concentration of sodium cephalexin in man given single intramuscular and intravenous injections
Authors: Gower P E , Dash C H , O'Callaghan Cynthia H
Published: April 2011

Healthy volunteers were given a single intramuscular (i.m.) injection of a solution of 1 g, 500 or 250 mg sodium cephalexin or an intravenous (i.v.) injection of 1 g. Following i.m. injection, mean peak serum levels were estimated by computer analysis to be 18.3, 17.9 and 8.2 μg ml−1 respectively. The mean serum level 15min after i.v. injection was 52.5 μg ml−1. The rate of recovery of cephalexin in the urine after i.m. injection was slower than after both i.v. injection and oral administration. Concentrations of cephalexin in the urine reached a higher maximum after i.v. than after i.m. injection, but were maintained for a shorter time. Analysis of the data after i.m. injection suggests the occurrence of a depot-like effect.
Gas-liquid chromatographic separation of the optical isomers of some “ephedrines” and “pseudoephedrines”
Authors: Beckett A H , Testa B
Published: April 2011

Gas-liquid chromatographic separation of the optical isomers of norephedrine, norpseudoephedrine, ephedrine, pseudoephedrine, N-ethylnorephedrine and N-ethylnorpseudoephedrine by means of their N-trifiuoroacetyl-L-prolyl derivatives has been investigated. A quantitative determination of the enantiomeric percentages was possible for the primary amines, and for all secondary amines except pseudoephedrine. The method is suitable for metabolic studies.
The effect of pH and of temperature on the stability and bioactivity of nystatin and amphotericin B
Authors: Hamilton-Miller J M T
Published: April 2011

In the presence of phosphate-citrate buffers, nystatin and amphotericin B are optimally stable between pH 5 and 7. Loss of biological activity followed first-order kinetics, except under acid conditions. Apparent energies, enthalpies, free energies and entropies of activation of the two antibiotics have been calculated at pH 7, and the two sets of figures are similar. Variation in pH between 5 and 8 appeared to have little effect of the activity of amphotericin B against Candida albicans, while nystatin was more active at pH values between 6 and 8. Nystatin was more active at lower incubation temperatures (30-25°), while amphotericin B appeared to be more active at 41°.
Rapid gas-liquid chromatographic estimation of antipyrine in plasma
Authors: Prescott L F , Adjepon-Yamoah K K , Roberts Elizabeth
Published: April 2011

A simple gas-liquid chromatographic method for the estimation of antipyrine in plasma is described. The drug is extracted from alkaline plasma into chloroform and after concentration is chromatographed directly using a mixed liquid phase of 0.5 % SE 30 and 0.5% Carbowax 20M. The standard deviation of the method for plasma containing 10–50 μg ml−1 of antipyrine was 2.8%. Compared with the standard spectrophotometric assay, antipyrine plasma concentrations were lower and the mean plasma half life in 12 patients was slightly but not significantly shorter.
A new modification for studying 5-HT uptake by blood platelets: a re-evaluation of tricyclic antidepressants as uptake inhibitors
Authors: Tuomisto Jouko
Published: April 2011

The effect of imipramine and other antidepressive drugs on 5-HT uptake by rabbit platelets was re-evaluated, since it had become obvious that, in previous studies, too high substrate concentrations and too long incubation times had been used. A Km of 1·8 times 10−7m was obtained for 5-HT uptake when 1 min incubation in plasma was used. Imipramine caused a half-maximal inhibition at 10−7m or lower concentration. When the platelet-rich plasma was diluted with buffer solution, only about 2 times 10−8m imipramine was required for 50% inhibition. This concentration is only 1/500 to 1/100 of concentrations described in most earlier data. In this study, other tricyclic drugs and phenothiazine derivatives were also much more effective than previously demonstrated. Their rank of potency order was, however, very similar to that earlier described. The correlation of uptake inhibition in platelets with 5-HT uptake inhibition in brain synaptosomes was found to be highly significant. It is concluded that the previous studies give valuable information on the relative potency of different drugs inhibiting 5-HT uptake. When the technique is modified as suggested by the present results, the level of uptake-inhibiting potency in an absolute sense is close to that described for other tissues, especially brain synaptosomes or slices. Therefore, platelets can more reliably be used as an easily obtainable model for nerve endings in uptake studies.