bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of the Ferguson principle to the antibacterial activity of mono- and multi-component solutions of quaternary ammonium surface-active agents
Authors: Laycock H H , Mulley B A
Published: April 2011

Critical micelle concentrations (cmc) have been measured by the surface tension method for binary mixtures of dodecyltrimethyl-ammonium bromide with tetradecyltrimethylammonium bromide, binary mixtures of C14/C16 homologues, a ternary mixture of the C12/C14/C16 compounds and additionally for each component individually. The antibacterial activities of the systems against Escherichia coli were determined by a British Standard Method (B.S. 3286: 1960). Thermodynamic activities of the solutions at two survivor levels, calculated from the physical and biological measurements, were sufficiently constant to sustain the Ferguson principle for these micelle-forming antibacterial agents. A theoretical treatment of micelle formation for multi-component solutions of surfactants gave cmc’s by calculation in close agreement with the experimentally determined values. The purity and composition of the surfactants was determined by gas liquid chromatography.
The effect of directly and indirectly acting sympathomimetic amines on bronchospasm in the guinea-pig during CO2 inhalation
Authors: Atkinson Judith M , Pun Lan-Queen , Rand M J
Published: April 2011

The bronchodilator effects of nine sympathomimetic amines were tested by reduction of histamine-induced bronchospasm in guinea-pigs. Their order of potency was: isoprenaline > adrenaline > noradrenaline > orciprenaline > ethylnoradrenaline > phenylephrine > amphetamine = tyramine > ephedrine. In guinea-pigs ventilated with 10% CO2 in air, there was a marked decrease in the bronchoconstrictor activity of histamine. Under these conditions, isoprenaline, adrenaline, noradrenaline and orciprenaline were as effective as bronchodilators as they had been in guinea-pigs ventilated with air, ethylnoradrenaline was less effective, phenylephrine, amphetamine and tyramine were completely inactive, and ephedrine potentiated the bronchoconstrictor action of histamine. After returning the guinea-pigs to ventilation with air, the bronchoconstrictor activity of histamine and the bronchodilator effects of the sympathomimetic amines were restored. The cardiovascular effects of histamine and of all the sympathomimetic amines used were diminished during ventilation with 10% CO2 in air and were restored after ventilation with air was resumed.
Selective determinations of amines and quaternary ammonium compounds as ion pairs with methyl orange by an automated method applicable to single dose analysis
Authors: Nyberg Lars
Published: April 2011

Aliphatic amines and quaternary ammonium compounds can be determined photometrically after extraction as ion pairs with methyl orange. Extraction conditions are calculated from constants for the extraction procedure and side-reactions. Methods for the selective determination of ammonium ions of different degrees of substitution are given. Quaternary ammonium ions are isolated by extraction at pH 12. The amines are extracted as ion pairs at pH 4.6 and selective determinations can be made after primary and secondary amines are masked by acetylation and primary amines by coupling with salicylic aldehyde. An automated application of the method on a Technicon AutoAnalyzer is presented. A complete analysis of a sample containing the four kinds of ammonium ions requires four separate runnings. The same basic manifold is used for all the runnings with some rearrangements for the masking procedures. The method has been tested on benzhexol, diethylpropion, dodecylamine, emepronium, N-hydroxyethylpromethazine, promethazine and protriptyline. Recoveries of about 100% with a relative variation of 1–2% were obtained.
Determination of piribenzil in urine containing a metabolite and dextropropoxyphene by an ion pair extraction method
Authors: Borg K O , Holgersson H , Lagerström P O
Published: April 2011

Piribenzil, an antispasmodic quaternary ammonium compound, has been determined quantitatively in human urine containing a metabolite of piribenzil and dextropropoxyphene. Ion pair extraction with bromothymol blue as counter ion was used and the extraction conditions were calculated from extraction constants and partition coefficients determined using methylene chloride as organic solvent. The determination was made by photometry in the range 5–50 μg of piribenzil methyl sulphate/ml of urine. The recovery was 97% ± 3%. The co-extraction of urine components such as nicotine, tyramine, tryptamine and choline was investigated by determination of constants for the partition of these compounds.
An investigation of the distribution coefficients of some androgen esters using paper chromatography
Authors: Bowen D B , James K C , Roberts Margaret
Published: April 2011

Rm values have been determined for four homologous series of androgen esters, using a Bush paper chromatography system, to assess the value of the ratio of the solubilities in the individual solvents (solubility ratio), as an estimate of distribution coefficient. The distribution coefficients were proportional to Rm values in all four series, and for three of these the proportionality constant was the same. Limitations in the use of RM values to predict biological effects have been pointed out.
Central hypotensive effect of L-3,4-dihydroxyphenylalanine in the rat
Authors: Henning M , Rubenson A
Published: April 2011

Mean arterial blood pressure was recorded through in-dwelling arterial catheters in conscious normotensive Sprague-Dawley rats. L-3,4-Dihydroxyphenylalanine (L-dopa) was given in various doses intraperitoneally, alone and after pretreatment with an inhibitor of dopa decarboxylase, α-hydrazino-α-methyl-β-(3,4-dihydroxyphenyl) propionic acid (MK 485) or seryl-2,3,4-trihydroxybenzylhydrazine (Ro 4–4602). L-Dopa (50 mg/kg) produced a hypertensive response which was abolished by MK 485 (100 mg/kg). A larger dose of L-dopa (200 mg/kg) after MK 485 caused a significant lowering of blood pressure after 15–20 min. After Ro 4–4602 (400 + 200 mg/kg), injection of L-dopa (200 mg/kg) had no significant effect on blood pressure. The hypotensive response to L-dopa (200 mg/kg) after MK 485 was not influenced by the central dopamine receptor blocking agent, spiroperidol (0.1 mg/kg), but could be completely inhibited by the dopamine β-hydroxylase inhibitor, bis-(4-methyl-1-homopiperazinyl-thiocarbonyl)disulphide (FLA 63) (40 mg/kg). Pretreatment with protripty-line (10 mg/kg) completely blocked the hypotensive effect of L-dopa after MK 485. In correlative biochemical experiments, levels of noradrenaline and dopamine were determined in brain, heart and femoral muscle. L-Dopa (200 mg/kg) alone caused a significant increase of dopamine levels in all tissues. After MK 485 and Ro 4–4602 L-dopa did not significantly increase the levels of dopamine in heart or femoral muscle; however, brain dopamine levels were increased more than after L-dopa alone, but brain dopamine levels after Ro 4–4602 were significantly lower than after MK 485, indicating some central decarboxylase inhibition by Ro 4–4602. L-Dopa alone reduced the noradrenaline content of the heart and this effect was prevented by MK 485 and Ro 4–4602. The results show that decarboxylation of L-dopa in both the central and the peripheral nervous system leads to an increase in blood pressure. Decarboxylation of L-dopa in the central nervous system only results in a hypotensive response, provided that high amounts of dopamine are formed in the brain. This effect was prevented by an inhibitor of dopamine β-hydroxylase but not by a dopamine receptor blocker. Therefore, a central noradrenaline mechanism seems to be involved. The presence of an intact membrane pump in noradrenaline neurons may be essential since protriptyline also blocked the hypotensive action.
The effects of calcium on adrenergic neuron blockade
Authors: Wilson J
Published: April 2011

The effects of increasing extracellular calcium were investigated on the responses to sympathetic nerve stimulation of three isolated organs; rabbit ileum, guinea-pig vas deferens and rabbit ear artery. A rise in the calcium concentration increased the responses of the ileum to low frequency stimulation, the maximum increase being obtained at 8.8 mM calcium. After partial blockade by guanethidine of the responses of the ileum to high frequency stimulation, raised calcium concentrations again increased the responses. The increase was similar in guanethidine-treated and untreated preparations and the maximum increase in both was obtained using 8.8 mM calcium. In the vas deferens and rabbit ear artery preparations an increase in extracellular calcium did not antagonize the blocking action of guanethidine. These experiments do not therefore support the theory that guanethidine acts by preventing the entry of calcium into the sympathetic nerve endings.
The effect of sodium salicylate on the release of acid phosphatase activity from rat liver lysosomes in vitro
Authors: Harford Deborah J , Smith M J H
Published: April 2011

Salicylate, in concentrations up to 10mM, does not inhibit the activity of the acid phosphatase liberated from rat liver lysosomes. The release of the enzyme from lysosomal preparations incubated with the drug depends on the pH of the incubation medium, the duration of incubation and the concentration of salicylate. It is concluded that salicylate does not influence lysosomal stability in vivo.
The relative purgative activities of 1,8-dihydroxyanthracene derivatives
Authors: Fairbairn J W , Moss M J R
Published: April 2011

The purgative activities of twelve different 1,8-dihydroxyanthracene derivatives including free anthraquinone, anthrone and dianthrone forms, anthraquinone O-glycosides and dianthrone O-glycosides were compared with senna pod powder using the production of wet faeces by mice as a criterion of purgation. The higher purgative activity of the dianthrone glycosides was confirmed for the compounds based on rhein. Sennidin (rhein dianthrone) was more active than had previously been reported. These highly active compounds had parallel dose response curves which were not parallel to those of the less active rhein anthrone, rhein, aloe-emodin and chrysophanol. Emodin and chrysazin were inactive in mice. The highly active compounds exerted a high activity during the initial 3 h after dosage while the less active compounds were virtually inactive during this period. Rhein anthrone appeared to act initially like the highly active primary sennosides, sennoside A and sennidin and later as the less active rhein. The results are discussed in relation to the mode of action of orally administered 1,8-dihydroxyanthracene derivatives.
A stability study of chloramphenicol in topical formulations
Authors: James K C , Leach R H
Published: April 2011

The stabilities of several chloramphenicol preparations have been investigated at ambient temperatures. The B.P.C ointment and eye ointment were stable over 2 years. The remainder retained more than 90% of their potencies after the following periods: ear drops B.P.C., 2 years, Drug Tariff cream, 5 months and eye drops B.P.C., 3 to 4 months. 15% hydrolysis occurred after autoclaving the eye drops, and 3 to 4% after heating with a bactericide. The latter sterilization process is recommended. Two assay procedures were employed, one estimating residual chloramphenicol by ultraviolet spectrophotometry after separation from decomposition products by thin layer chromatography and the other determining the main degradation product (1-p-nitrophenylpropan-1,3-diol-2-amine) colorimetrically.
Flow properties of aluminium soap-hydrocarbon systems
Authors: STEPHENS J S
Published: April 2011

Organogels prepared from aluminium stearate and liquid paraffin in concentrations of 0·5 to 17·0% by weight were examined using a rotational viscometer fitted with cone and plate. Parameters used to characterize the flow curves of these gels were plastic viscosity, apparent viscosity at fixed rates of shear and the estimated area of the hysteresis loop. The influence of temperature and aluminium stearate concentration on the shapes of the curves was examined. Concentration of aluminium stearate and temperature were found to influence both thixotropic behaviour and the rate of recovery after shear. A minimum concentration of 1·5 to 2·0% by weight of aluminium stearate appeared to be necessary for the formation of the gel structure.
Nuclear magnetic resonance studies of interactions between cetomacrogol and phenol
Authors: JACOBS J J , ANDERSON R A , WATSON T R
Published: April 2011

Phenol solubilized in cetomacrogol micelles appears to accumulate principally in the polyoxyethylene region and appears not to be randomly distributed along the polyoxyethylene chains. When concentrations of phenol are sufficiently high, a phenol-cetomacrogol-rich phase separates. This phase contains relatively little water and the phenol molecules may be randomly distributed along the polyoxyethylene chains. Transfer of molecules between the phases of these cloudy systems is relatively slow.
Differences in the stereospecificity of closely related compounds; a reinvestigation of the enantiomers of procyclidine, benzhexol and their metho- and etho-salts
Authors: BARLOW R B
Published: April 2011

The findings of Duffin & Green (1955) that there are very large differences in the stereospecificity of some closely related phenyl-cyclohexylhydroxypropyl compounds have been confirmed, and it has been shown that this cannot be ascribed to any errors attached to the methods for assessing biological activity, or to inadequate resolution of some of the compounds. Measurement of the affinity constants of the compounds for the postganglionic acetylcholine receptors of the guinea-pig ileum showed that the (+)-and (-)-isomers of benzhexol differ only 5·5-fold in affinity whereas the (+)-and (-)-isomers of procyclidine differ at least 375-fold. This big variation in stereospecificity indicates that changes in one part of the molecule markedly affect the binding of the rest of the molecule and the effects are different in the different enantiomers. It is not possible to interpret the difference between the affinity of the isomers simply in terms of the fit, or failure to fit, of one group, such as the hydroxyl, attached to the asymmetric centre. In the five pairs of compounds tested, the stereospecificity was greatest in the compounds with lowest affinity, which is the reverse of what would be predicted from Pfeiffer's rule.
The action of isoprenaline on the perfused vessels of the rabbit ear
Authors: DAY M D , DIXON HAZEL V R
Published: April 2011

In rabbit isolated perfused ear preparations isoprenaline in doses of 1 to 5 μg caused a vasodilatation which was specifically blocked by propranolol. In a minority of experiments larger doses of isoprenaline (5 to 10 μg) caused vasoconstriction. The vasodilatations to isoprenaline were increased by raising vascular tone with barium chloride whereas ergotamine and sympathetic stimulation were relatively ineffective. In the isolated ear central artery preparation, isoprenaline caused a vasoconstriction due to α-receptor stimulation. A vasodilator response due to β-receptor stimulation was revealed when perfusion pressure was raised with barium chloride. It is concluded that α- and β-adrenergic receptors are present in both preparations but a higher proportion of β-receptors are present in the whole ear.
The selective uptake of mercury by myocardial infarcts in the rat
Authors: LESZKOVSZKY G P , SZÁNTHÓ VILMA
Published: April 2011

Rats with myocardial infarcts, sham operated and control animals were treated with methoxyethyl mercury chloride (MEMC) intra-peritoneally or with mercamphamide intravenously or intra-peritoneally and the mercury content in the hearts determined spectrophotometrically with dithizone after various time intervals. After MEMC treatment there was no difference between the amounts of mercury found in the hearts of rats with myocardial infarcts and controls. After injection of mercamphamide, mercury was taken up by hearts of rats with myocardial infarcts while those of sham operated and control animals remained free of mercury. Optimal results were yielded by 1 h experiments made within the first 24 postoperative hours. The selective uptake of mercury from organo-mercurials is much dependent on the organic part of the molecule present in the given individual compound.
Non-competitive spasmolytics as antagonists of Ca++-induced smooth muscle contraction
Authors: SIMONIS A M , ARIËNS E J , VAN DEN BROEKE J J W
Published: April 2011

The spasmolytic drugs papaverine, phenpropamine, Cxn 2 (1-methyl-amino-3,3,5-trimethylcyclohexane), khellin, cyclandelate, magnesium chloride, cocaine, 2,4-dinitrophenol and KCN antagonize various types of spasmogens, such as acetylcholine or histamine, non-competitively. They are assumed to act at some level in the excitation-contraction process common to the various spasmogens. Ca++ is essential for the induction of a contraction by the spasmogens. In the non-competitive action of some spasmolytics, Ca++ is postulated to be involved. To detect possible differences in their mechanism of action the various spasmolytics were tested against Ca++ acting as a pseudo-spasmogen on the K+-primed taenia caeci of the guineapig in a Ca++-free medium. Although different mechanisms of action for the various spasmolytics are to be expected, they all behaved similarly with respect to Ca++ in that they all caused a parallel shift in the log dose-response curve of Ca++ to higher concentrations.
Dissolution rate studies using the B.P. disintegration apparatus
Authors: KHALIL SALEH A H , ALI L M M , KHALEK M M ABDEL
Published: April 2011

The application of the B.P. disintegration apparatus in dissolution rate studies has been examined. The dissolution profiles of some brands of chloramphenicol capsules and tolbutamide tablets have been examined at various tube speeds with and without the guided disc. For both drugs a tube speed of 20 strokes/min gave the optimum difference in dissolution rates. The effect of the guided disc depended on the disintegration time of the product tested. For poorly disintegrating products the use of the guided disc resulted in about twofold increase in dissolution whilst insignificant effect was found for products with fast dissolution rate.
The protective effect of gallate antioxidants on emulsions and solutions of benzaldehyde
Authors: NIXON J R , HAQUE R S UL , CARLESS J E
Published: April 2011

In solubilized systems of benzaldehyde-water-antioxidant-cetomacrogol the ratio of benzaldehyde to gallate antioxidant is of prime importance. Provided this ratio is constant, the rate of oxidation and the induction period of the systems is independent of cetomacrogol concentration. The efficiency of the different gallates appears to be the same in L1 micellar systems. In disperse systems the maximum oxidation rate is related to the total surface area of the droplets and to the quantity of benzaldehyde present in the disperse phase. Because changes in the relative concentration of the components of the system alter both the phase volume ratio and the total surface area a protection factor concept (ratio of the rate of oxidation of benzaldehyde in the absence of gallate: rate in the presence of gallate) was used to define the effect of gallates on the maximum rate.
The role of cyclic AMP in isoprenaline-induced cardiac necroses in the rat
Authors: MARTORANA P A
Published: April 2011

Single administrations of isoprenaline chloride (6–36 μg/kg, s.c.) resulted in the appearance of acute myocardial necroses in the rat within 24 h. The percentage of animals with lesions was directly related to the dose of isoprenaline. Dibutyryl cyclic AMP (1–50 mg/kg, i.p.) induced myocardial lesions of the same type, however the percentage of animals affected was not dose-dependent. Pretreatment with theophylline (75 mg/kg, s.c.) administered to inhibit cardiac phosphodiesterase activity, induced a 48-fold reduction in the ED50 of isoprenaline and potentiated the nucleotide-induced cardiac lesions which became dose-dependent. Thus, a mediatory role for cyclic AMP in the isoprenaline-induced cardiac necroses in the rat is suggested.
Mechanism of MJ 1999-induced blockade of neuromuscular transmission
Authors: PATEL V K , KELKAR V V , JINDAL M N
Published: April 2011

MJ 1999 [4-(isopropylamino-1-hydroxyethyl)methanesulphonanilide hydrochloride] produced a dose-related blockade of indirectly evoked twitches of the rat diaphragm, without materially altering the effects of direct stimulation. The magnitude of blockade was comparable whether the indirect stimulation was at 1/s or 1/20 s. The blockade was less pronounced at 25° than at 34°. The blockade was antagonized by neostigmine, potassium chloride, succinyl-choline, tetraethylammonium, adrenaline, isoprenaline and, to some extent, by noradrenaline. Blockade by MJ 1999 was additive to that due to tubocurarine; large concentrations of yohimbine, tolazoline, phenoxybenzamine and dihydroergotamine quickly antagonized MJ 1999 blockade. Small concentrations of adrenaline, isoprenaline, tolazoline or yohimbine prevented MJ 1999 blockade. MJ 1999 had no effect on nerve conduction. It is proposed that MJ 1999 has a two-fold mode of action at the neuromuscular junction; a curare-like effect and an action on β-receptors.
The effect of heat, pH and some buffer materials on the hydrolytic degradation of sulphacetamide in aqueous solution
Authors: MEAKIN B J , TANSEY I P , DAVIES D J G
Published: April 2011

The hydrolytic degradation of sulphacetamide has been investigated under anoxic conditions over a wide range of pH values and at different temperatures. The sole breakdown product is sulphanilamide. The reaction is essentially independent of pH (measured at 25°) over the range 5 to 11, but is subject to catalysis by buffer constituents. Below pH 4 specific hydrogen ion catalysis occurs. Calculation of activation parameters leads to the conclusion that sulphacetamide solutions can be satisfactorily autoclaved provided they are not subsequently refrigerated.
Demonstration of 3,4-dihydroxy[14C]benzoic acid and [14C]vanillic acid after administration of [14C]noradrenaline in the rat
Authors: PESKAR B , HELLMANN G , HERTTING G
Published: April 2011

Rats were injected with 40 μCi (±)-[1-3H]noradrenaline and 10 μCi ±-[1-14C]noradrenaline. Three fractions with a decreased 3H:14C ratio were isolated from the urine by a combined alumina adsorption-ethyl acetate extraction procedure. Two of the fractions were identified as [14C]vanillic acid and 3,4-dihydroxy[14C]benzoic acid, respectively. Vanillic acid represented between 1.5 and 3.0% of the total [14C]activity excreted within 24 h and the contribution of dihydroxybenzoic acid was 0·2-0·5%. The third fraction with a decreased 3H: 14C ratio has not been identified and represented about 2% of the total [14C]activity excreted within 24 h. After monoamine oxidase blockade with 100 mg/kg of iproniazid, the excretion of vanillic acid, 3,4-dihydroxybenzoic acid and the unknown fraction was greatly diminished. The probability that these three substances represent those metabolites arising simultaneously with the formation of tritium water from (±)-[1-3H]noradrenaline is discussed.
A phase-rule study of multiple-phase formation in a model emulsion system containing water, n-octanol, n-dodecane and/a non-ionic surface-active agent at 10 and 25°
Authors: MARLAND J S , MULLEY B A
Published: April 2011

A four-component emulsion system containing the non-ionic surfactant C8H17 (O·CH2·CH2)6OH has been investigated, particularly in regions in which liquid crystal or more than two condensed phases are formed. Liquid crystal does not exist in the binary surfactant-water system at 25° but extensive regions form when the organic liquids octanol and dodecane are present, although these are not joined to the main two-liquid regions of the emulsion system. The surfactant is almost completely dissolved in the aqueous phase in water-dodecane mixtures but when substantial amounts of octanol are also present the partition coefficient is reversed in favour of the organic phase. At certain intermediate compositions three liquid phases are present. The significance of these results to the system as an emulsion are briefly discussed.
The kinetics of dissolution for a non-disintegrating standard substrate
Authors: WITHEY R J
Published: April 2011

The dissolution profiles for a 1 cm sodium chloride cube, which was considered to represent a standard non-distintegrating substrate, were obtained in seven kinds of dissolution apparatus. The results were used to assess experimental reproducibility and apparatus variables and to examine the adherence of the kinetics of the dissolution process to theoretical rate laws.
The mechanism of the inhibitory action of salicylate on glutamyl-transfer ribonucleic acid synthetase in vitro
Authors: BURLEIGH MARY , SMITH M J H
Published: April 2011

Salicylate inhibits glutamyl-transfer ribonucleic acid synthetase by simple competitive inhibition with respect to glutamate and mixed competitive-non-competitive inhibitions with ATP and tRNA. It is suggested that competition between salicylate and amino-acid explains the variable inhibition of the synthetases by the drugs in vitro. The action of salicylate is consistent with a mechanism for glutamyl-tRNA formation involving a concerted interaction of all three substrates. The drug may selectively interfere with protein synthesis in vivo.
The neuromuscular blocking activity of some monoquaternary androstane derivatives
Authors: BAMFORD D G , BIGGS D F , DAVIS M , PARNELL E W
Published: April 2011

The neuromuscular blocking activity of some 3- or 17-monoquaternary derivatives of 3β,17β-dipyrrolidin-1′-yl-5α-androstane has been examined in the cat. 3-Monoquaternary salts were, in general, more potent than the 17-monoquaternary salts. It was concluded that the presence of a quaternary group in position 3 is an important determinant of potency in this series of androstane derivatives.
Some 5-hydroxytryptamine-like actions of fenfluramine: a comparison with (+)-amphetamine and diethylpropion
Authors: SOUTHGATE P J , MAYER SUSAN R , BOXALL ELIZABETH , WILSON A B
Published: April 2011

The 5-hydroxytryptamine (5-HT)-like effects of fenfluramine have been investigated in mice in two different experiments. In a behavioural test in mice pretreated with tranylcypromine, fenfluramine caused stereotyped changes which were similar to those produced by 5-hydroxytryptophan (5-HTP) and were antagonized by methysergide or pretreatment with p-chlorophenylalanine (PCPA). Like 5-HTP, fenfluramine reduced the conditioned response in a one-trial conditioning test, an effect antagonized by methysergide or by PCPA pretreatment. The reduction in the conditioned response caused by a maximal electroconvulsion was also antagonized by PCPA, an effect prevented by 5-HTP. Equivalent anorectic doses of (+)-amphetamine and diethylpropion caused a small increase in stereotyped behaviour, but this was not modified by methysergide; both anorectic drugs were inactive in the one-trial conditioning test. It seems probable that the observed actions of fenfluramine are caused indirectly through the release of endogenous brain 5-HT.
Effect of amphetamine on the uptake, release and effectiveness of xylocholine in the guinea-pig vas deferens
Authors: DEAN H G , HUGHES I E
Published: April 2011

Amphetamine sulphate will both reverse and prevent the adrenergic neuron blocking action of xylocholine (TM10 bromide) on the response of the guinea-pig isolated vas deferens to transmural electrical stimulation. A concentration of amphetamine sulphate capable of reversing the effect of xylocholine does not produce a significant reduction in the tissue concentration of 14C-TM10 iodide in the vas deferens. Although amphetamine reduces the rate of uptake of xylocholine, it does not prevent uptake. Comparisons of tissue concentrations with the degree of blockade produced in the normal and the amphetamine-treated vas deferens suggest that if the actions of amphetamine are to be accounted for entirely by displacement of xylocholine or by changes in uptake of xylocholine, only a very small percentage of the total tissue content of xylocholine can be involved in the production of its effects.
Structure-activity relations for anticholinergic 2[1-aryl(or cyclohexyl)-1-hydroxy-1 -phenyl]methyl-1,3-dioxolans
Authors: BRIMBLECOMBE R W , INCH T D , WETHERELL JANET , WILLIAMS NANCY
Published: April 2011

The syntheses and configurational assignments of some 4-dimethyl aminomethyl-2[1-aryl (or cyclohexyl)-1 -hydroxy-1-phenyl]methyl-1,3-dioxolans are described. The anticholinergic potency of the 4-dimethylaminomethyl-2[l-cyclohexyl-l-hydroxy-l-phenyl]methyl-1,3-dioxolans, both in tertiary and quaternary form, depends principally on the configuration of the benzylic carbon atom, secondly on the C-2 configuration and thirdly, and to a much lesser extent, if at all, on the C-4 configuration. The dioxolans, which are derived formally from 4-dimethylaminomethyl-2-methyl-1,3-dioxolan methiodide (or its tertiary analogue) by replacement of the 2-methyl substituent by a 2[l-aryl (or cyclohexyl)-l-hydroxy-l-phenyl]methyl group and the glycollates which are derived formally from acetylcholine (or its tertiary analogue) by corresponding substitution of the acetoxymethyl group have closely similar anticholinergic potencies.
The ganglion blocking activity of diastereoisomeric dimethylaminobornyl acetates and their methiodides
Authors: COOPER G H , GREEN D M , RICKARD R L , THOMPSON PAMELA B
Published: April 2011

Some diastereoisomeric dimethylaminobornyl acetates and their methiodides have been prepared and tested for ganglion blocking activity. Included in these compounds was an enantiomeric pair and associated quaternary salts. These optical antipodes displayed virtually no difference between their actions at the ganglion. Differences between the activities of the least and most potent diastereoisomers was limited to a factor of about five. Assays were made upon the cat superior cervical ganglion and also the guinea-pig vas deferens preparation the successful quantitative use of which is described.
The reversal of experimental cardiac arrhythmias by indoramin (Wy 21901)
Authors: ALPS B J , HILL MADELINE , FIDLER K , JOHNSON E S , WILSON A B
Published: April 2011

Indoramin was approximately equipotent with (±)-propranolol but more potent than lignocaine in reversing adrenaline-induced multiple ventricular ectopic beats and ventricular tachycardia in halothane-anaesthetized cats. Indoramin was more potent than either propranolol or lignocaine in reversing ouabain-induced ventricular tachycardia or fibrillation to sinus rhythm. The local anaesthetic activity of indoramin was three times greater than that of procaine and lignocaine and twice that of (±)-propranol and quinidine when assessed by the guinea-pig wealtest. Experiments on the guinea-pig isolated ileum supporting a local anaesthetic action of indoramin showed that nicotine contractions were reduced by indoramin whereas acetylcholine responses were unaffected. Based on the evidence presented and that published elsewhere, it is considered likely that indoramin abolishes adrenaline-induced arrhythmias by a combination of membrane stabilization and blockade of myocardial α-adrenoceptors whereas ouabain arrhythmias may be reversed by membrane stabilization alone.
Methods for the preparation of lysophosphatidylcholine
Authors: MERRYFIELD DANUTA S , WREN J J
Published: April 2011

The surfactant and solubilizing properties of lysophosphatidylcholine (LPC) could have industrial uses if it became available in technical quantity and purity. The two most promising routes for obtaining it are isolation from cereal starches and mono-deacylation of egg phosphatidylcholine (PC). Baker's yeast autolysed by Letters's method yielded up to 0·3 % of LPC. The phospholipase A activity of pancreatin powder gave 80 % of the theoretical yield of LPC under optimum conditions; modifications designed to facilitate scale-up reduced the yield. Base-catalysed glycerolysis at 75° gave 23 % of the theoretical yield of LPC, and a reaction between PC and ethanolamine up to 45%. The crude product from ethanolamine after acetone precipitation gave an emulsifier containing LPC, PC and long-chain N-2-hydroxyethylamide.
The effect of suspensions on the bactericidal activity of m-cresol and benzalkonium chloride
Authors: BEAN H S , DEMPSEY G
Published: April 2011

The bactericidal activity of experimental aqueous suspensions of light kaolin with m-cresol as preservative agreed closely with the activity of aqueous m-cresol solutions not brought into contact with kaolin (i.e. aqueous reference solutions). In contrast the activity of light kaolin suspensions with benzalkonium chloride was lower than that of aqueous benzalkonium chloride solutions because of adsorption of preservative by the kaolin. Suspensions containing benzalkonium chloride possessed a greater activity than the corresponding supernatant solutions removed from contact with the kaolin, owing to some of the bactericide adsorbed on the kaolin becoming available to the bacteria. Suspensions of procaine penicillin with benzalkonium chloride gave similar results to those for kaolin.
Antagonism by propranolol of the inhibitory effect of phenoxybenzamine on noradrenaline uptake in vivo
Authors: CHANG C C , WANG WUAN-HSIANG
Published: April 2011

The reduction of noradrenaline stores and [3H]noradrenaline concentration in the heart of mice and rats induced by phenoxybenzamine-treatment, alone or in combination with cold-stress, was prevented by propranolol. Propranolol also antagonized a similar effect induced by phentolamine but not that induced by other noradrenaline uptake inhibitors, such as desipramine, cocaine, guanethidine and reserpine. Analysis of the time-course of antagonism by propranolol indicates that it was evident only when the β-adrenoceptor blocking agent remained in the body. The inhibitory effect of phenoxybenzamine on noradrenaline stores reappeared when propranolol was excreted. Propranolol alone did not change cardiac noradrenaline stores or [3H]noradrenaline. It is concluded that the restoration of reflexly increased adrenergic discharge to normal, because of unmasking of spare α-adrenoceptors resulting from β-adrenoceptor blockade by propranolol rather than competition for binding at the active site of phenoxybenzamine, is responsible for the observed antagonism.
The action of azapropazone, oxyphenbutazone and phenylbutazone on lysosomes
Authors: LEWIS D A , CAPSTICK R B , ANCILL R J
Published: April 2011

Azapropazone, oxyphenbutazone and phenylbutazone have a stabilizing action on isolated lysosomes over a wide concentration range but a lytic action at high concentrations. The lytic action of phenylbutazone was greater than the other drugs. Phenylbutazone at a high concentration was found to accelerate the breakdown of lysosomes in isolated stomach preparations in vitro. Phenylbutazone was found to have a greater ulcerogenic action than azapropazone in rats and rabbits. Tissues removed from rats and rabbits dosed with phenylbutazone showed evidence of lysosomal damage when examined histochemically for acid phosphatase. In contrast, tissues from control and azapropazone-treated rats showed no evidence of lysosomal damage. Sections of rat gut incubated with azapropazone and phenylbutazone in vitro showed similar results. The possibility is discussed that drugs in high concentration may damage lysosomes in the gastrointestinal tract. It is suggested that lysosomal damage may contribute to the ulcerogenic action of the drugs in vivo.
The excretion of hydroxyamylobarbitone in man after oral administration of amylobarbitone and hydroxyamylobarbitone
Authors: GROVE J , TOSELAND P A
Published: April 2011

The excretion of hydroxyamylobarbitone in man has been measured over six days after an oral dose of 200 mg of sodium amylobarbitone. The biological half-life of hydroxyamylobarbitone determined from “Sigma-minus” plots ranged between 16·8 and 22 h in seven subjects, in another subject the half-life was 34·4 h. The effects of increasing urine flow on the amount of hydroxyamylobarbitone excreted after ingestion of 200 mg of sodium amylobarbitone were assessed. A subject normally excreting 34% of the dose as hydroxyamylobarbitone excreted 45% of the dose as metabolite while taking chlorothiazide as a diuretic. With the same subject taking increased fluids to produce a greater urine flow 41% of the dose was excreted as hydroxyamylobarbitone. Hydroxyamylobarbitone is not bound to plasma proteins and when an aqueous solution of 50 mg of hydroxyamylobarbitone was taken by mouth, 57% of the dose was eliminated in the first 8 h and 91% in the first 24 h. The half-life for ingested hydroxyamylobarbitone was 5·7 h, showing that the rate of elimination of this metabolite is faster than its rate of formation when amylobarbitone is ingested.
The influence of methyl substitution on the N-demethylation and N-oxidation of normethadone in animal species
Authors: BECKETT A H , MITCHARD M , SHIHAB A A
Published: April 2011

N-Monodemethylation and N-oxidation were shown to be the major routes of metabolism of normethadone, (—)-methadone and (—)-isomethadone in vitro by hepatic microsomal preparations from rat, rabbit, guinea-pig, mouse and hamster. The rate of N-oxidation was decreased and the rate of N-demethylation was increased by the introduction of the methyl substituent into normethadone; the configuration of the methyl substituent influenced these processes. Km and Vmax values were determined for liver microsomal N-demethylation of normethadone, (—)-methadone and (—)-isomethadone by rat and guinea-pig and for the N-oxidation of normethadone by guinea-pig. The use of selective inhibitors showed that N-demethylation was not preceeded by N-oxidation in these compounds.
The effect of ethanol on phenobarbitone and pentobarbitone absorption into rat blood and brain
Authors: COLDWELL B B , TRENHOLM H L , THOMAS B H , CHARBONNEAU S
Published: April 2011

Male rats administered [14C]phenobarbitone (50 mg/kg) or [14C]-pentobarbitone (30 mg/kg) simultaneously with either 15% ethanol (3 g/kg) or saline intraperitoneally were killed 5, 10 or 20 min after injection. The radioactivity in the blood, whole brain and different brain areas was measured. Phenobarbitone was absorbed more slowly into the blood and brain than pentobarbitone. Ethanol-treated rats had significantly higher phenobarbitone concentrations than the saline-treated controls in the blood, whole brain, cerebrum and cerebellum up to 10 min after injection. Pentobarbitone concentrations were not significantly altered by ethanol. Barbiturate concentrations in the cerebral cortex were lower than in other regions of the brain. The brain: blood barbiturate ratios were not appreciably changed by ethanol. It is concluded that ethanol (15%) given intraperitoneally aided the transport of phenobarbitone across the peritoneum and hence increased the rate of its absorption into the blood and brain.
Infrared identification of sulphonamides using attenuated total reflection
Authors: EDWARDS D
Published: April 2011

The infrared spectra of ten sulphonamides have been determined by attenuated total reflection and compared with transmission spectra. No major differences were found in the positions and shapes of the main absorption peaks and it was possible to use ATR to identify sulphacetamide sodium in eye-drops and in eye ointments.
Administration of two or more related drugs to investigate the effect of molecular modification and formulation on drug absorption, metabolism and excretion
Authors: BECKETT A H , BROOKES L G
Published: April 2011

Two or more related drugs of the amphetamine class were simultaneously administered to man under acidic urine control, their urinary excretion being examined by gas-liquid chromatography. This was shown to be a suitable procedure for determining the effect of molecular modification and formulation on drug absorption, metabolism and excretion.
The effects of substituting tetrazole for carboxyl in two series of anti-inflammatory phenoxyacetic acids
Authors: DRAIN D J , DAVY B , HORLINGTON M , HOWES J G B , SCRUTON J M , SELWAY R A
Published: April 2011

Series of o-phenylcarbamoyl- and o-benzamido-phenoxymethyl tetrazoles and o-phenylcarbamoylphenoxyacetic acids have been synthesized. Anti-inflammatory activity was measured by the phenyl benzoquinone writhing test in mice and the rat foot carrageenan oedema test. Potency in the two o-benzamido substituted series could not be related with structure in a satisfactory manner. Introduction of substituents into the benzene rings of the o-phenylcarbamoyl substitued series led to complex changes. When the phenoxy ring was unsubstituted, introduction of meta- and para-substituents possessing high +ve π constants into the o-phenylcarbamoyl ring led to increased potency, and each tetrazole was appreciably more potent than the corresponding acid. When the o-phenylcarbamoyl ring was unsubstituted meta- and para-substituents with high +ve π constants introduced into the phenoxy ring caused increases in potency in the acid series but not in the tetrazole series, and each acid was more potent than the corresponding tetrazole. The two tetrazoles found to be the most active in the mouse writhing test 5-[2-(3,4-dichlorophenylcarbamoyl)phenoxymethyl]tetrazole (compound 12T, SNR.2337) and 5-[4-chloro-2-(3-trifluoromethylphenyl-carbamoyl)phenoxymethyl]tetrazole (compound 22T, SNR.2420) were selected for study in a series of other anti-inflammatory tests.
Neuromuscular blocking and ganglion blocking activities of some acetylcholine antagonists in the cat
Authors: BOWMAN W C , WEBB SANDRA N
Published: April 2011

The potencies of tubocurarine, gallamine, pancuronium, benzoquinonium, hexamethonium and mecamylamine in blocking neuromuscular transmission in the soleus muscle, and in blocking contractions of the nictitating membrane evoked by preganglionic sympathetic stimulation have been compared in cats under chloralose anaesthesia. On a molar basis, pancuronium was about 8 times and benzoquinonium about 2·5 times more potent than tubocurarine in blocking the soleus muscle; gallamine was less than half as potent, mecamylamine about 128 times and hexamethonium about 380 times less potent. In blocking the superior cervical ganglion, mecamylamine was about 17 times more, tubocurarine was about 5 times more and pancuronium about twice as potent as hexamethonium. Benzoquinonium was about half as potent as hexamethonium, and gallamine about 5 times less potent. The results emphasize that the shorter distance between charged centres, as in hexamethonium, reduces affinity for muscle receptors but does not necessarily enhance affinity for ganglion receptors, and from the point of view of deductions concerning the configuration of the ganglionic receptor, the ganglion blocking potencies of some neuromuscular blocking drugs should be taken into account.
The influence of formulation variables on phase inversion temperatures of emulsions as determined by a programmed viscometric technique
Authors: SUNDERLAND V B , ENEVER R P
Published: April 2011

A programmed temperature rise viscometric technique has been used to examine the influence of formulation variables on the phase inversion temperatures (P.I.T.) of oil-in-water emulsions stabilized with mixed polyoxyethylene alcohol surfactants. Using a heating rate of 0·5° min−1, the P.I.T. was defined either by a sharp change in apparent viscosity when recording shear stress-rate of shear rheograms for successive emulsion samples, or by the change in shear stress with time for a single emulsion sample. With an overall concentration of 6·00% w/w surfactant mixture of Brij 92 and Brij 96, the P.I.T. was found to rise in an approximately linear fashion as the HLB increased towards the optimum value. When the surfactant concentration was related to the aqueous or oil phase and these phase ratios varied, the P.I.T. changed in a complex manner. Water-soluble additives caused marked changes in the P.I.T. For example, 5·0% w/w sodium chloride depressed the P.I.T. by 17° and 5·0% w/w calcium chloride caused an 11° fall, whereas 2·0% w/w propylene glycol produced a 6° rise. These results followed the same trend as the cloud point of 1·0% w/w aqueous solutions of Brij 96 containing these additives. Linear correlations were obtained between the cloud point and P.I.T. data from which the effect of additives upon emulsion stability may be monitored.
Chemoprophylactic agents in schistosomiasis: eremanthine, costunolide, α-cyclocostunolide and bisabolol
Authors: BAKER P M , FORTES C C , FORTES ELIZABETH G , GAZZINELLI G , GILBERT B , LOPES‡ J N C , PELLEGRINO J , TOMASSINI T C B , VICHNEWSKI WALTER
Published: April 2011

The wood oils of the trees Eremanthus elaeagnus Sch.-Bip., Vanillosmopsis erythropappa Sch.-Bip. and Moquinea velutina Bong. inhibit penetration of cercariae of the trematode Schistosoma mansoni. The effect is due to the presence of α,β-unsaturated sesquiterpene lactones of which three, eremanthine (I), costunolide (III) and α-cyclocostunolide (V), have been characterized. The sesquiterpene alcohol (-)-bisabolol (II) present in two of the oils is weakly active while dihydro-β-cyclocostunolide (VI) which lacks the unsaturated lactone function is inactive. I and V react with the sulphydryl group of cysteine, and their activity may be related to inhibition of sulphydryl groups in cercarial enzymes.
Some actions of amantadine on peripheral tissues
Authors: HEIMANS R L H , RAND M J , FENNESSY M R
Published: April 2011

Amantadine has been tested on several peripheral preparations. It depressed responses of the chick isolated oesophagus to nicotine and preganglionic parasympathetic nerve stimulation without depressing responses to acetylcholine. It did not affect the amplitude or duration of action potentials in toad sciatic nerve. It enhanced the effects of noradrenaline and dopamine while reducing the effect of tyramine on the coaxially stimulated guinea-pig ileum, isolated central artery of the rabbit ear and spontaneously beating guinea-pig isolated atria preparations. Amantadine enhanced the depressor effect of dopamine in the rabbit.
Effects of amantadine on uptake and release of dopamine by a particulate fraction of rat basal ganglia
Authors: HEIMANS R L H , RAND M J , FENNESSY M R
Published: April 2011

Amantadine, in vitro, produced dose-dependent blockade of dopamine uptake into a synaptosome-rich particulate fraction of an homogenate of the basal ganglia of rats. A concentration of 3·6 times 10−6M was required to inhibit uptake by 50%. Diethazine was less potent in blocking dopamine uptake, the equiactive concentration being 8·0 times 10−6M. Amantadine and (+)-amphetamine in concentrations in excess of 10−5M caused the release of small quantities of added dopamine from the particulate fraction.
The assessment of β-adrenoceptor blocking potency and cardioselectivity in vitro and in vivo
Authors: BAIRD J R C , LINNELL JENNIE
Published: April 2011

The β-adrenoceptor blocking potencies and cardioselectivities (versus tracheal smooth muscle) of propranolol, practolol and M & B 17803A have been assessed on in vitro and in vivo guinea-pig preparations. Propranolol was found to be potent but non-selective, practolol to be less potent but cardioselective. M & B 17803A resembled practolol in potency but had a more modest degree of cardioselectivity in vivo. These observations suggest that the procedures used form a simple scheme which permits a probably relevant assessment of β-adrenoceptor blocking potency and cardioselectivity.
Effects of fenfluramine on the adrenergic system
Authors: BABULOVA A , COTILLO P , BONACCORSI A , PODVALOVA I
Published: April 2011

The influence of fenfluramine on sympathetic transmission has been examined in various intact and isolated preparations. Fenfluramine both facilitated and inhibited the responses elicited by the sympathetic stimulation according to the dose administered and the preparation used. Fenfluramine, to a lesser extent than amphetamine, antagonized, in some preparations, the neuron blocking action of guanethidine. Fenfluramine did not antagonize the sympathomimetic effects elicited by amphetamine in the isolated atria and the isolated vas deferens unless very high concentrations of both drugs were used.