bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of p-hydroxylation of amphetamine in its peripheral mode of action
Authors: Freeman J J , Sulser F 
Published: April 2011

Abstract
Desipramine completely abolished the blood pressure response to (+)-amphetamine in the rat, whereas the tricyclic antidepressant iprindole did not reduce this response. Since both tricyclic drugs inhibit the aromatic hydroxylation of amphetamine, these studies do not support the hypothesis that hydroxylated metabolites of amphetamine, p-hydroxyamphetamine and p-hydroxynorephedrine are essential for the peripheral sympathomimetic effects of amphetamine.
Pharmacokinetics of haloalkylamines: cyclization and distribution in blood in vitro and in vivo
Authors: Ross Svante B 
Published: April 2011

Abstract
The cyclization of N-(5-chloropentyl)-N-methylaniinoaceto-2,6-xylidide hydrochloride (RAD 150) and N-(5-bromopentyl)-N-methylaminoaceto-2,6-xylidide hydrobromide (RAD 154) in red blood cells of rats and rabbits was examined under in vitro and in vivo conditions. The rate of cyclization was much slower in plasma and blood than in a buffer solution, probably due to influence of protein binding of the compounds. The tertiary amines disappeared rapidly from the blood cells in vitro and in vivo and the piperidinium derivative (RAD 179) formed from the haloalkylamines disappeared almost as rapidly as the tertiary amines from the plasma in vivo. In contrast, the efflux of RAD 179 formed in the blood cells was slow (T½ for rabbit erythrocytes: 9 h in vitro; 8 h in vivo) following a 1st order reaction. RAD 179 itself was only to a small extent taken up in the blood cells.
Skin irritants of Euphorbia fortissima
Authors: Kinghorn A D , Evans F J 
Published: April 2011

Abstract
By means of a combination of partition and chromatographic methods six irritant constituents were isolated from the fresh latex of Euphorbia fortissima. Compounds A-D were di-esters of the common parent diterpene 12-deoxyphorbol, and compounds E and F were mono-esters of the same diterpene. The fresh latex had an irritant dose 50% (ID50) on mice of 0.64 μg μ1−1. Compounds A-D are short-acting irritants reaching a maximum activity within 4 h of application to the skin, whilst the monoesters maintained potent irritant effects for up to 24 h. Selective hydrolysis of the di-esters at the C–20 primary ester group also produced mono-esters of greater potency after 24 h. An increase in the length of the fatty acid located at C–13 produced greater biological activity in both the mono- and di-ester groups.
Metabolism of phenothiazines: identification of N-oxygenated products by gas chromatography and mass spectrometry
Authors: Essien E E , Cowan D A , Beckett A H 
Published: April 2011

Abstract
The solid inlet mass spectra of the N-oxide and N-oxide sulphoxide metabolites of promazine, chlorpromazine and methotrimeprazine have been determined at different temperatures and compared with the mass spectra of the main thermolytic product of the N-oxides and N-oxide sulphoxides obtained during combined gas chromatographymass spectrometry. Diagnostic ions were produced by direct insertion of the compounds at ambient temperature into the mass spectrometer. These ions distinguish the N-oxides of arylalkyl tertiary amines from the N-oxygenated derivatives of primary and secondary arylalkylamines.
The diffusion of penicillin G and ampicillin through phospholipid sols
Authors: Padfield John M , Kellaway I W 
Published: April 2011

Abstract
The self-diffusion coefficients of penicillin G and ampicillin have been determined at 25° in water and in the presence of a swamping concentration of electrolyte. The antibiotics diffused through phospholipid dispersions at a reduced rate due to interaction with the lipid aggregates. Ampicillin diffused through the phosphatidylcholine and phosphatidylethanolamine dispersions more rapidly than penicillin G, whereas the latter diffused more rapidly through the lysophosphatidylcholine dispersions. Estimates of binding have been made from these data and compared with those obtained from equilibrium dialysis studies. Surface tension measurements indicated that the antibiotics exhibited minimal surface activity. These results have been correlated with data obtained in other studies and a possible explanation has been advanced for the reported differences in in vivo activity of penicillin G and ampicillin.
The instrumentation of a Zanasi LZ/64 capsule filling machine
Authors: Cole G C , May G 
Published: April 2011

Abstract
The dosator system of a Zanasi LZ/64 capsule filling machine was modified and strain gauges were fitted. These were used to measure the forces on the powder being filled during compaction and ejection. The patterns of those forces produced were shown to differ between different materials and between lubricated and unlubricated materials. Tentative reasons for the observed differences have been suggested.
Emulsion stabilization by non-ionic surfactants: the relevance of surfactant cloud point
Authors: Florence A T , Madsen Florence , Puisieux F 
Published: April 2011

Abstract
The effect of various additives, electrolytes and non-electrolytes, on the cloud point of non-ionic surfactants has been studied. Additives which salt-out the polyoxyethylene chains of the surfactants cause decreased stability of oil-in-water emulsions by decreasing the true hydrophile-lipophile balance (HLB) of the surfactant; additives such as sodium iodide and propanol salt-in the non-ionic surfactants and result in an increase in the effective or true HLB of the system. The latter additives do not increase the hydration of the polyoxyethylene chains but their effect must be on the structure of water so that the heat of hydration of the chains is altered. Experiments with free films of the aqueous surfactant (Brij 96) show that thinning rates are markedly affected by the additives, but there is little effect on the equilibrium thickness of the films (ca 11 nm). Nonetheless the thickness at the transition from thick film to equilibrium black film decreases with increasing cloud point of the solution indicating increased stability. The importance of structure formation in the liquid film separating the emulsion globules was demonstrated.
The evaluation of a column-type dissolution apparatus
Authors: Groves M J , Alkan M H , Deer M A 
Published: April 2011

Abstract
An improved column-type dissolution apparatus is described. The column of the apparatus is built from standard screw-cap connected ‘Sovirel’ glass tubes which should enable inter-apparatus variability to be reduced. The main problem with this type of device is the build up of back pressure as fragments from the disintegrating solid dosage form progressively block the filtration system, itself necessary to stop the solution process and present the solution for analysis. A simple type of light-activated switch is therefore used which works across the indicator float of a flow meter to drive a motor connected to a needle valve. As the float falls the motor is switched on to open the valve and increase the flow rate until the float rises again and causes the motor to switch off. Observation on the dissolution characteristic of dyed lactose tablets and the injection of dye solutions into the flowing stream of liquid around tablets showed that there was back-flow of solution at Reynolds Numbers below 10 but visible instability of flow at Re &gt; 100. Over a range of flow rates between Re 10–70 the mass of drug released at a given time was a direct function of flow rate for a film coated product but an inverse function for a sugar coated tablet. The results are discussed in relation to the main problems which can be experienced with a column-type dissolution apparatus.
Microiontophoretic studies of the effects of false transmitter candidates and amphetamine on cerebellar Purkinje cells
Authors: Kostopoulos G K , Yarbrough G G 
Published: April 2011

Abstract
The effects of microiontophoretic applications of equivalent doses (ejection times and currents) of noradrenaline, amphetamine, octop-amine and p-hydroxynorephedrine on the spontaneous firing of Purkinje and unidentified cells in the cerebellum of rats were examined. In addition, the effects of amphetamine on Purkinje cells were examined in nimals pretreated with the tyrosine hydroxylase inhibitor, α-methyl-tyrosine (α-MpT) or with a combination of reserpine plus α-MpT. The results indicate that the “false transmitters” are weak agonists when compared to noradrenaline in inhibiting the firing of Purkinje cells. The results of the iontophoretic studies with amphetamine are not consistent with a pre-synaptic releasing effect by amphetamine at noradrenergic synapses in the cns since the efficacy of amphetamine on Purkinje cells was unaltered after pretreatment with α-MpT or α-MpT plus reserpine.
Intra- and extraneuronal formation of the two major noradrenaline metabolites in the cns of rats
Authors: Braestrup C , Nielsen M 
Published: April 2011

Abstract
The two major noradrenaline metabolites in the rat brain, total 3-methoxy-4-hydroxyphenylglycol(MOPEG) and total 3,4-dihydroxy-phenylglycol (DOPEG), were measured by a new analytical procedure after intraventricular (i.v.t.) injection of [3H]noradrenaline or [3H]dopamine. I.v.t. injection of [3H]noradrenaline to rats with a 6-hydroxydopamine-induced destruction of nerve terminals in the central nervous system, resulted in an increased accumulation of 3H-MOPEG compared to 3H-DOPEG. On the contrary, reserpine induced a greater increase in 3H-DOPEG than in 3H-MOPEG accumulation when these two metabolites were formed from [3H]noradrenaline synthesized in vivo by i.v.t. injection of [3H]dopamine. These results indicate that the formation of DOPEG and MOPEG occur with some preference intra- and extraneuronally, respectively. The results, however, also show that these two formations sites should not be considered as specific.
The gas chromatographic determination of atenolol in biological samples
Authors: Scales Bryan , Copsey Paul B 
Published: April 2011

Abstract
Methods are described for the gas chromatographic determination of the β-adrenoceptor blocking agent atenolol (ICI 66,082 Tenormin) in whole blood, serum, tissue and urine. The method involves the extraction of the free base from the prepared biological sample into an organic solvent mixture. Further purification is done by back-extracting the base into dilute acid from which, after basification it is extracted again into organic solvent. Any atenolol in the residue remaining after solvent evaporation is converted into a heptafluoro-butyrate derivative ready for gas chromatography. Use of an electron-capture detector enables concentrations as low as 0.01 μg ml−1 body fluid and 0.04 μg ml−1 tissue to be measured.
The development of a radioimmunoassay for cannabinoids in blood and urine
Authors: Teale J D , Forman Elvyne J , King L J , Piall Evelyn M , Marks V 
Published: April 2011

Abstract
Antibodies, for use in radioimmunoassay, have been raised in sheep by immunization with a conjugate of Δ9-tetrahydrocannabinol hemisuccinate and bovine serum albumin. Antiserum titre and avidity were increased by successive booster doses of conjugate. The high degree of non-specific binding encountered in the radioimmunoassay of cannabinoids was reduced by the use of the solubilizing detergent Triton X-405 and by restricting protein concentration in the assay medium. Plasma samples were deproteinized with ethanol before assay, but urine was directly assayed. High avidity antibodies and high specific activity [3H]- Δ9-tetrahydrocannabinol permitted the detection of 50 pg of cross-reacting cannabinoids–-a sensitivity of 7.5 ng ml−1 of plasma and 1.0 ng ml−1 of urine. Whilst apparently specific for the three-ringed cannabinoid nucleus, the assay antiserum cross-reacted with several cannabinoids, both natural compounds and metabolites. Partial identification of cross-reacting cannabinoids was achieved by the use of pure compounds and by the assay of plasma and urine samples collected from rabbits given pure cannabinoids intravenously.
Characterization of an angiotensin II-fluorescamine derivative
Authors: Forget Gilles , Heisler Seymour , Park Won Kil , Sirois Pierre , Gagnon Denis , Regoli Domenico 
Published: April 2011

Abstract
The coupling of fluorescamine (4-phenylspiro[furan-2(3H),l′-phthalan]-3,3′ dione) to angiotensin II to form a fluorescent derivative was studied. Complete reaction of the peptide below concentrations of 10−4m could be achieved with a fluorescamine concentration of 0.3 mg ml−1 of acetone at pH 8.3, and the lowest concentration detectable by fluorescence spectroscopy was 100 pmol ml−1. The derivative, as prepared did not react with ninhydrin, and no fluorescence was generated when fluorescamine was reacted with (1-Sar)-ATII. These data suggest that fluorescence is generated only through the coupling of fluorescamine to the N-terminal primary amine of ATII. The ATII-fluorescamine derivative has the same intrinsic activity on the contraction of rat colon (elevenfold loss of affinity), and on the release of fluorogenic corticosteroids from bovine adrenal cortical slices (sixfold loss of affinity) compared to ATII. Water-hydrolysed fluorescamine and Asp-fluorescamine did not contract rat colon preparations; the contractile response to ATII-fluorescamine was blocked by (8-Leu)-ATII, a specific ATII antagonist. These findings suggest that the ATII fluorophore shares a common receptor site with the native octapeptide. The rate loss of biological activity of the ATII-fluorescamine derivative was appreciably lower than that observed for ATII. The present study suggests that the ATII fluorescamine derivative can be substituted for radioactively-labelled ATII for use in a variety of applications.
The interaction of aminoalkylaminoanthraquinones with deoxyribonucleic acid
Authors: Double J C , Brown J R 
Published: April 2011

Abstract
A series of aminoalkylaminoanthraquinones have been prepared as potential intercalating agents. The binding to DNA of these compounds and the known intercalating drugs chloroquine, lucanthone, daunorubicin and doxorubicin has been characterized by spectrophotometric titration. The association constant for the interaction with DNA has been determined for each compound from a Scatchard plot. The compounds synthesized had association constants between 0.5 and 4.2 × 106 compared with 0.93, 0.90, 3.10 and 2.49 × 106 for chloroquine, lucanthone, daunorubicin and doxorubicin respectively.
The effect of mucin on the bioavailability of tetracycline from the gastrointestinal tract; in vivo, in vitro correlations
Authors: Braybrooks M P , Barry B W , Abbs E T 
Published: April 2011

Abstract
The bioavailability of tetracycline in the presence and absence of a porcine gastric mucin dispersion (1% w/v) has been studied by in vivo perfusion of the rat small intestine, the rat everted gut, a diffusion cell technique and the Sartorius Absorption Simulator Apparatus. In the presence of the mucin preparation an approximate 50% reduction in the numerical values of each of the parameters used to measure the tetracycline movement across the membrane was found. The physiological significance of each technique and the methods themselves are discussed. Interaction of tetracycline with the porcine gastric mucin preparation is considered in relation to the molecular structure of mucus. The results suggest the drug is bound in some way, as yet undefined, to the mucin macromolecule.
An improved implantation pellet for rapid induction of morphine dependence in mice
Authors: Hui K S , Roberts M B 
Published: April 2011

Abstract
A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.
Dissolution and bioavailability of the anhydrate and trihydrate forms of ampicillin
Authors: Hill S A , Jones K H , Seager H , Taskis C B 
Published: April 2011

Abstract
The solubilities and intrinsic dissolution rates of ampicillin anhydrate and trihydrate in distilled water and dilute hydrochloric acid at 37° have been measured. The dissolution rates of these materials from loose filled hard gelatin capsules were determined and the in vivo bioavailabilities of the compounds compared. Small differences in the in vitro behaviour of the anhydrate and trihydrate forms were recorded but the in vivo availability of the two compounds was the same.
The determination of phenothiazine drugs in pharmaceutical preparations by a difference spectrophotometric method
Authors: Davidson A G 
Published: April 2011

Abstract
A method is described for the rapid determination of phenothiazine drugs in a wide variety of pharmaceutical preparations. The drugs are determined by a difference spectrophotometric technique based upon the absorbance of the sulphoxide derivative of the drug relative to the absorbance of a solution of the underivatized drug. The sulphoxide derivatives are formed rapidly and quantitatively at room temperature by the addition of a solution of peroxyacetic acid, prepared by the slow reaction of hydrogen peroxide and glacial acetic acid on standing. The difference absorbance of the solutions is proportional to the concentration of the phenothiazine drug in the preparation and is specific for the intact drug in the presence of oxidative and photochemical decomposition products, colouring and flavouring agents, excipients and most co-formulated drugs.
In vitro metabolism of l-phenyl-2-(n-propylamino) propane (N-propylamphetamine) by rat liver homogenates
Authors: Coutts R T , Dawson G W , Beckett A H 
Published: April 2011

Abstract
In vitro incubation of (±)-N-(n-propyl)amphetamine (NPA) with the 12 000 g supernatant fraction of rat liver homogenate resulted in the formation of two N-oxygenated products identified as N-hydroxy-1-phenyl-2-(n-propylamino)propane and N-[(1-methyl-2-phenyl) ethyl]-1-propanimine N-oxide by g.l.c, g.l.c.-m.s. and t.l.c. Amphetamine, phenylacetone, benzyl methyl ketoxime, and a previously unreported metabolite N-(2-hydroxy-n-propyl) amphetamine were also isolated. Increasing the pH of the incubation mixture from 7·4 to 8·4, or in vivo pretreatment of rats with 3-methylcholanthrene caused an increase in the in vitro metabolic N-oxidation of NPA, whereas pretreatment with phenobarbitone or NPA did not. The presence of SKF 525-A in incubation mixtures reduced the amount of C-oxidation and to a lesser degree of N-oxidation. When (+)-NPA or (–)-NPA was used as substrate, C-oxidation was favoured with the former and N-oxidation with the latter.
A proposed mechanism for the biphasic vasoconstrictor responses to 5-hydroxytryptamine and methysergide in the rabbit ear artery
Authors: Apperley Eira , Humphrey P P A 
Published: April 2011

Abstract
Rabbit ear arteries were isolated and perfused at a constant flow rate so that the perfusate flowed into the fluid bathing the adventitial surface of the artery. Submaximal doses of intraluminally applied noradrenaline injected as a bolus into the perfusion fluid produced transient monophasic vascoconstrictor responses. In contrast, similarly administered 5-hydroxytryptamine (5-HT) or methysergide caused prolonged biphasic vascoconstrictor responses. The extraluminal/intraluminal potency ratios for noradrenaline, 5-HT and methysergide were 230, 15 and 6 respectively, which indicates that 5-HT and methysergide are relatively more potent when administered extraluminally than noradrenaline. Cocaine (3·10 × 10−5 mol litre−1) markedly increased the potency of extraluminally administered noradrenaline and converted the monophasic responses produced by noradrenaline to biphasic responses. It is concluded that under the experimental conditions used 5-HT and methysergide produced biphasic responses by an action on the medial smooth muscle firstly via the intraluminal surface and secondly an additional direct action via the adventitial surface. Noradrenaline's extraluminal potency is low because of its neuronal uptake and hence the responses are normally monophasic.
Enhancement of ethanol-induced withdrawal convulsions by blockade of 5-hydroxytryptamine receptors
Authors: Blum Kenneth , Wallace Jack E , Schwertner Harvey A , Eubanks J D 
Published: April 2011

Abstract
Male Swiss-Webster mice were made physically dependent on ethanol using the ethanol vapour inhalation technique. Animals pretreated with methysergide, a known 5-hydroxytryptamine receptor blocking agent, had significantly greater alcohol-induced withdrawal convulsions than saline pretreated controls. These findings suggest that the reduction of 5-HT at receptor sites may result in the augmentation of the withdrawal convulsions.
Some biological and pharmacological properties of inflammatory exudates
Authors: Doherty N S , Robinson B V 
Published: April 2011

Abstract
Inflammatory exudates were obtained from polyester sponges which had been implanted subcutaneously in rats four days previously. This material was found to be anti-inflammatory when injected into other rats in which carrageenan pleurisy had been induced. At a dose of 600 mg kg−1 exudate inhibited the formation of pleural effusion, emigration of both neutrophils and mononuclear cells and the accumulation of β-glucuronidase and lactic dehydrogenase. The same dose of sponge exudate did not however inhibit the increased vascular permeability induced in the rat skin or rat foot following injection of 5-hydroxytryptamine, histamine, prostaglandin E1, or bradykinin. Furthermore sponge exudate did not reduce the haemolytic complement titre of rat serum either in vivo or in vitro. The possible mechanism of anti-inflammatory action of exudate is discussed.
Potentiation of dopaminergic transmission by phosphodiesterase inhibitors and cyclic nucleotides
Authors: Pentreath V W , Berry M S 
Published: April 2011

Abstract
Experiments were made to determine whether cyclic AMP plays a role in transmission at identified dopaminergic synapses in the water snail Planorbis corneus. Intracellular stimulation of a specific dopamine neuron produces direct inhibitory postsynaptic potentials (ipsps) in a number of other neurons. These ipsps, which are mediated by dopamine, were potentiated by as much as 120% by caffeine, theophylline or dibutyryl cyclic AMP, although they were unaffected by cyclic AMP and prostaglandin E1. Caffeine and theophylline also potentiated the inhibitory response to dopamine, applied to the postsynaptic neurons by perfusion or iontophoresis, but the effects were generally much smaller (maximum potentiation 30%). The results provide evidence that postsynaptic cyclic AMP is involved in transmission at these synapses, but that the phosphodiesterase inhibitors may also have a presynaptic effect.