bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxation of intestinal smooth muscle and calcium movements
Authors: Tomiyama A , Takayanagi I , Takagi K 
Published: April 2011

Abstract
The effects of papaverine, isoprenaline and N6,2′-O-dibutyryl 3′,5′-cyclic adenosine monophosphate (DiBu.C-AMP) on calcium movements in the taenia from the guinea-pig caecum have been investigated and compared with the effects of phenylephrine. Papaverine and DiBu.C-AMP antagonized the contraction of KCl-depolarized muscle induced by CaCl2 and increased 45Ca-efflux from the taenia. Papaverine also significantly depressed 45Ca-uptake by this preparation. These findings suggest that papaverine impairs the availability of calcium to the contractile system and that there may be a correlation between relaxation and increase of 45Ca-efflux. The action of DiBu.C-AMP resembles that of papaverine but its potency is less.
Plasma protein binding of 7-hydroxy-Δ1-tetrahydrocannabinol: an active Δ1-tetrahydrocannabinol metabolite
Authors: Widman M , Nilsson I M , Nilsson J L G , Agurell S , Borg H , Granstrand B 
Published: April 2011

Abstract
7-Hydroxy-Δ1-tetrahydrocannabinol, which is a pharmacologically and psychologically active metabolite of Δ1-tetrahydrocannabinol in man, has been shown by equilibrium dialysis and ultrafiltration to be bound 94–99% to plasma proteins. Further experiments, using the [14C]labelled compound, with agarose and Polyacrylamide gel electrophoresis and ultracentrifugation suggest that albumin, α1-lipoprotein and, to a minor degree, also β-lipoprotein are involved in the protein binding of 7-hydroxy-Δ1-tetrahydrocannabinol in blood plasma.
The effects of changes in ionic environment and modification of adrenergic function on the vascular responses to sympathomimetic amines
Authors: George A J , Leach G D H 
Published: April 2011

Abstract
The responses to each of four sympathomimetic amines: noradrenaline 200 ng, octopamine 50 μg, metaraminol 20 μg and tyramine 100 μg were studied in the perfused rat mesentery preparation. Perfusion with Ca2+- and Mg2+-free solutions potentiated the responses to all four amines compared with control responses obtained during normal Krebs perfusion. Under perfusion conditions using either normal or Ca2+- and Mg2+-free Krebs solution, nialamide and reserpine retained their characteristic effects on the responses to each amine. Cocaine and desipramine abolished the responses to tyramine but potentiated those to noradrenaline and metaraminol under all perfusion conditions. The responses to each of the amines were only antagonized by ouabain when Ca2+ ions were present in the perfusion solution. It is concluded that perfusion with Ca2+- and Mg2+-free solution interferes with the normal uptake mechanisms occurring in the adrenergic neuron.
The effect of corticosterone on extraneuronal amine uptake and effector response in rat salivary glands
Authors: Almgren Olle , Jonason Jan 
Published: April 2011

Abstract
The effect of corticosterone on effector cell response to noradrenaline in vivo and on extraneuronal amine uptake in vitro has been investigated in rat submaxillary glands. When tissue slices were incubated with [3H]noradrenaline the level of extraneuronally retained radioactive material was found to be markedly reduced at a concentration of 10 μg ml−1 of corticosterone after inhibition of neuronal uptake by protriptyline. Corticosterone in a dose of 10 mg kg−1 was found to markedly potentiate the secretory response to noradrenaline in vivo, when the neuronal uptake of noradrenaline was blocked by protriptyline (10 mg kg−1, i.p.). Inhibition of neuronal uptake alone by protriptyline or of the extraneuronal uptake alone by corticosterone in the doses used here did not affect the dose-response curve for noradrenaline, at least not in its lower part. The data thus clearly show that the extraneuronal amine uptake of rat salivary glands is blocked by corticosterone and that this extraneuronal uptake might be regarded as a mechanism of importance for the inactivation of the adrenergic transmitter.
Spectrophotofluorometric and gas-liquid chromatographic methods for the estimation of mexiletine (Kö 1173) in plasma and urine
Authors: Kelly J G , Nimmo J , Rae R , Shanks R G , Prescott L F 
Published: April 2011

Abstract
Methods are presented for the spectrophotofluorometric and gas-liquid chromatographic determination in plasma and urine of the anti-arrhythmic compound, mexiletine (Kö 1173). Both methods involve extraction of the drug from alkaline plasma with ether. In the spectrophotofluorometric method the compound is re-extracted into 0&#x006d;̇05n HCl and emission intensity determined at 300 nm with activation at 228 nm. In the chromatographic method the drug is acylated during evaporation of the ether. Both butyryl and acetyl derivatives could be used. Use of a nitrogen-sensitive detector increased the sensitivity and selectivity of the method and allowed more rapid analyses. There was good agreement between results obtained by spectrophotofluorometric and chromatographic methods.
Uptake of [3H]5-hydroxytryptamine and [3H]noradrenaline by slices of rat brain incubated in plasma from patients treated with chlorimipramine, imipramine or amitriptyline
Authors: Tuck J R , Punell G 
Published: April 2011

Abstract
Great interest has been focused in recent years on the purported role of monoamines in the depressive syndrome (for review see McClure, 1971). Monoamine systems in the brains of various species have been mapped out (Fuxe, 1965; Ungerstedt, 1971) and noradrenaline nerve terminals have been demonstrated in human cerebral cortex (Nyström, Olsson & Ungerstedt, 1972). Tricyclic antidepressants have been shown to be effective in about 60% of depressions treated (Bennet, 1967). These drugs affect the monoamine neuron by inhibiting the uptake of the released transmitters noradrenaline and/or 5-hydroxytryptamine (5-HT) through the membrane pump of the nerve terminals. Various tricyclic antidepressants have different profiles of potency in inhibiting the uptake into noradrenaline and 5-HT nerve terminals, each drug having its own pattern (Carlsson, Corrodi & others, 1969; Shaskan & Snyder, 1970; Lidbrink, Jonsson & Fuxe, 1971; Ross, Renyi & Ögren, 1972). We have previously studied the active uptake of [3H]noradrenaIine (3H-NA) and [3H]5-hydroxytryptamine (3H-5-HT) into their respective nerve terminals by using slices of rat cerebral cortex incubated in human plasma which was drawn from patients before and during treatment with antidepressant drugs (Hamberger & Tuck, 1973).
The interaction of penicillins with phospholipids
Authors: Padfield John M , Kellaway I W 
Published: April 2011

Abstract
The interaction of the antibiotics, penicillin G and ampicillin, with sonicated sols of phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine has been examined by Sephadex gel nitration and dynamic dialysis. Nuclear magnetic resonance spectroscopy provided evidence of a predominantly hydrophobic interaction between the antibiotics and the phospholipids, phosphatidylserine and phosphatidylcholine. Confirmation of hydrophobic interaction was provided by a rheological investigation of the effects of urea and guanidine hydrochloride on the antibiotic-phospholipid complex. Penicillin G was found to interact to a greater degree than ampicillin, a result which is of interest in the light of present knowledge of in vivo activity of these antibiotics.
The activity of β-adrenoceptor blocking agents in protecting mice from the cardiotoxic effects of ouabain
Authors: Lavender Marjorie K , Parkes M W 
Published: April 2011

Abstract
A method is described for the assessment of the protective activity of drugs against the lethal effect of intravenously infused ouabain in mice. Electrocardiographic studies confirmed that protection is exerted against a cardiotoxic action of the glycoside. Activities are quoted for some β-adrenoceptor blocking agents. Both (-)- and (+)-enantiomers of propranolol were active but only the (-)-enantiomer of sotalol and INPEA-drugs devoid of membrane-stabilizing properties.
Behavioural and biochemical interaction between caffeine and l-dopa
Authors: Stromberg Ulf , Waldeck Bertil 
Published: April 2011

Abstract
The modification by caffeine of the effects of different doses of l-dopa on locomotor activity and catecholamine levels in brain was investigated in mice. Caffeine, which in the dose used caused moderate locomotor stimulation by itself, did not alter the depressant effect on motility of medium doses of l-dopa. The hyperkinetic effect of higher doses of l-dopa was, however, potentiated by caffeine. Biochemically the increase in dopamine levels seen after a dose of l-dopa was enhanced by caffeine. It is suggested that at least part of the potentiating effect of caffeine on the l-dopa induced hypermotility is related to the increased cerebral levels of dopamine.
Papaver bracteatum Lindl.—a new plant source of opiates
Authors: Fairbairn J W , Hakim F 
Published: April 2011

Abstract
Certain strains of P. bracteatum Lindl. are reported to contain in the roots significant quantities of thebaine, which can be used for the production of codeine and other opiates. Results from plants raised from Iranian seeds and grown near London for 4 to 5 years are presented. The botanical and chemical characters correspond closely to those of the active strain Halle III described by Böhm (1970) and enable this plant to be clearly distinguished from the closely related P. orientale L. The thebaine content of the roots was 0.25 % which is much lower than the value of 0.7 to 1.3% reported in Halle III roots. The fruiting tops, however, were also investigated and found to contain significant amounts of thebaine in field conditions. If tops were harvested in the summer and roots in the autumn, about 15 kg thebaine per hectare should be produced from our strain grown in the conditions described. This compares favourably with about 1 kg alkaloids per hectare from Turkish opium production or even the 3 kg per hectare from the high yielding Indian farms.
Intestinal absorption, intestinal distribution, and excretion of [14C] labelled hyoscine N-butyl bromide (butylscopolamine) in the rat
Authors: Pentikäinen P , Penttilä Aneri , Vapaatalo H , Hackman R 
Published: April 2011

Abstract
Butylscopolamine was labelled with 14C and its gastrointestinal absorption, biliary and urinary excretion, enterohepatic circulation and gastrointestinal distribution were examined in anaesthetized rats. Biliary excretion was the main elimination route of intra-portally administered [14C]butylscopolamine, with 42% of the dose recovered in the bile during 12 h. About 6% of the radioactivity administered orally as [14C]butylscopolamine was excreted in the bile and 1.2 % in the urine during 24 h, which indicates poor gastrointestinal absorption of butylscopolamine in the rat. When collected radioactive bile was readministered intrajejunally, only about 7% of the radioactivity was recovered in bile and urine during 12 h, which suggests that only a small fraction of butylscopolamine and its metabolites engage in an enterohepatic circulation. After oral administration of [14C]butylscopolamine, radioactivity was found to accumulate in the wall of the distal small intestine, and about 20% of the dose was found in this tissue 24 h after drug administration. As a result, local anti-acetylcholine effects of butylscopolamine might be expected.
An examination of acid-base equilibria of 1,4-benzodiazepines by spectrophotometry
Authors: Barrett J , Smyth W Franklin , Davidson I E 
Published: April 2011

Abstract
Changes of ultraviolet absorption spectra with pH in solution were used to determine pKa values for six 1,4-benzodiazepines. Diazepam, chlordiazepoxide and medazepam as a result of protonation of the molecule in acidic solutions, were found to each have one pKa, while two pKa values were observed for oxazepam, nitrazepam and lorazepam, because of protonation in acid and deprotonation of the neutral molecule in alkaline media. The spectra are explained by considering them to be superimposed spectra of the two benzene rings, one mono-substituted and one tri-substituted, within the molecule. Sites of protonation (principally at nitrogen atoms in position 4 in the diazepine ring) and deprotonation (for oxazepam, nitrazepam and lorazepam) are predicted and the differences in the observed pKa values explained.
Metabolic N- and α-C-oxidation of norephedrine by rabbit liver microsomal fractions and synthesis of the metabolic products
Authors: Beckett A H , Jones G R , Al-Sarraj D S 
Published: April 2011

Abstract
The products of metabolism of norephedrine by 10 000 g fractions of rabbit liver microsomes have been shown to be norephedrine hydroxylamine, l-hydroxy-2-oxo-l-phenylpropane oxime, 1-hydroxy-2-oxo-1-phenylpropane, 1,2-dihydroxy-l-phenylpropane (erythro). N-Oxidation was at least as important as α-C-oxidation. The synthesis and properties of the metabolic products are described.
The dissolution of salicylic acid in micellar solutions of polysorbate 20
Authors: Rees Judith A , Collett J H 
Published: April 2011

Abstract
Dissolution rates of salicylic acid in micellar solutions of polysorbate 20 have been determined at pH 1·0 to 4·0 using a pH-stat to maintain the pH. At any one pH, as the concentration of polysorbate 20 was increased up to 12% w/v, the dissolution rate increased, but a further increase up to 20% w/v polysorbate 20 only slightly increased the dissolution rate. At any one concentration of polysorbate 20 the dissolution rate increased linearly as the pH was increased. The dependence of dissolution rate on such parameters as viscosity of the dissolution medium, diffusion layer thickness and diffusion cofficient has been examined.
Application of orthogonal functions to spectropolarimetric analysis of some penicillins
Authors: Wahbi A M , Ebel S 
Published: April 2011

Abstract
The orthogonal function method is extended to correct for interferences in spectropolarimetric analysis. The method has been applied to the determination of some penicillins in presence of the degradation product penicilloic acid. The results obtained suggest that the method can be widely applied for similar problems.
A new colorimetric method for the determination of methyldopa
Authors: Khalil S K Wahba , Salama R B 
Published: April 2011

Abstract
A rapid and convenient method is described for the determination of methyldopa in pharmaceutical preparations. This is based on measuring the intensity of the orange colour, developed on reacting methyldopa with thiosemicarbazide in alkaline medium, at 490 nm. The colour obeys Beer’s law in a concentration range of 2·0-10 μ-g ml−1. Since the catecholic function with free adjacent positions is required for the development of the colour, the method is highly specific.
The induction of ethanol dependence and the ethanol withdrawal syndrome: the effects of pyrazole
Authors: Littleton J M , Griffiths P J , Ortiz A 
Published: April 2011

Abstract
Daily administration of an inhibitor of alcohol dehydrogenase (pyrazole, 1 m mol kg−1, i.p.) appeared to prevent the development of metabolic tolerance to ethanol administered chronically to mice by inhalation, but increased the duration and intensity of the behavioural change associated with ethanol withdrawal, despite the absence of any marked difference in blood or brain ethanol and acetaldehyde concentrations during ethanol administration in the two groups. (Pyrazole-treated mice were exposed to lower concentrations of ethanol.) Changes in brain monoamine concentrations which occur in mice during chronic ethanol administration were not prevented by pyrazole, but differed in time course under these conditions. Repeated administration of pyrazole intraperitoneally caused weight loss and hypothermia in mice, whether or not ethanol was also given. It is concluded that the combination of pyrazole and ethanol is probably not capable of separating primary effects of chronic ethanol administration from secondary (metabolic) effects, and that inhibition of alcohol dehydrogenase is unlikely to be the sole reason for the potentiation of the ethanol withdrawal syndrome by pyrazole.
Metabolism of nealbarbitone
Authors: Gilbert J N T , Millard B J , Powell J W , Whalley W B , Wilkins B J 
Published: April 2011

Abstract
The human metabolism of 5-allyl-5-neopentylbarbituric acid (nealbarbitone, Censedal), taken orally, has been studied. Comparison of the gas chromatography—mass spectra of extracts from urine with the spectra of model compounds showed nealbarbitone diol (III) to be the only urinary metabolite present in significant amount (about 30–40% of dose); the rate of excretion of diol reached a maximum about 36 h after ingestion of a single 300 mg dose. Treatment of nealbarbitone with a model oxidase of the Udenfriend type resulted only in oxidation of the allyl side-chain to the 2-oxopropyl derivative, in low yield.
The choice of paper and thin-layer chromatographic systems for the analysis of basic drugs
Authors: Moffat A C , Clare B 
Published: April 2011

Abstract
Thirty-seven paper and thin-layer chromatographic systems in general use for the analysis of basic drugs have been examined. Their discriminating powers were measured, both individually and when used in combination. The better systems were found to be thin-layer systems of silica gel sprayed with 0·1n NaOH, dried and run using one of the following solvents: (1) chloroform-methanol (90:10), (2) cyclohexane-toluene-diethylamine (75:15:10) and (3) acetone. A thin-layer cellulose system using n-butanol-water-citric acid (87:13: 0–48) was suitable if speed was not a requirement and a reversed phase paper system run with an aqueous buffer solution (pH 4·58) at 95† was the fastest system examined. Any of these five systems could be used in combination since their correlation coefficients were never higher than 0·61.
The effect of particle size and shape on the flow and failure properties of procaine penicillin powders
Authors: Pilpel N , Walton C A 
Published: April 2011

Abstract
A study has been made of the effects of particle size and particle shape on the shear and tensile properties of batches of dried procaine penicillin powders whose particle shapes were varied by crystallization from different solvents. The following correlations have been established between the mechanical parameters of the powders and their particle size and shape. log C/T = 1·706 − 0·213 log (V/S) — 1·36 αs.v.a.; (n − 1) = 1·329 + 0·0083 (V/S) − 0·128 αs.v.a.; tan Δ= 0·812 + 0·0057 (V/S) + 0·025 αs.v.a.; FF = 6·52 + 0·434 (V/S) − 0·528 αs.v.a. The findings are discussed in relation to the design of filling equipment for unit doses of penicillin.
The influence of additives on the in vitro release of drugs from hard gelatin capsules
Authors: Newton J M , Razzo F N 
Published: April 2011

Abstract
A factorially designed experiment has been used to assess the total percentage of drug released from hard gelatin capsules in vitro as a function of (a) the drug—the drugs being nitrofurantoin, nitrofurazone, oxytetracycline dihydrate and tetracycline hydrochloride; (b) the diluent—the diluents being lactose, Primojel and Dry-Flow starch; (c) the quantity of diluent, either 20 or 80%; (d) the presence (at a 1 % level) and absence of magnesium stearate and (e) the presence (at a 1 % level) and absence of sodium lauryl sulphate. Treatment of the results by analysis of variance, in 5,4, 3 and 2 factor combinations, indicates that the influence of a given factor is often dependent on the other factors. These interdependencies take the form of either a variation in the extent of an effect or the reversal of an effect. The influence of drug and level of diluent show interdependencies of the former kind. Hence, whilst the overall average for drug release indicates that the drugs can be ranked in the ascending order: nitrofurantoin &lt; nitrofurazone &lt; oxytetracycline &lt; tetracycline, the interactions predict that the quantitative ratios of 1:1·8:2·7:5·1 for the drugs above will vary when an additive is present and according to the additive. The rank order will, however, remain unchanged. Similarly, the higher level of diluent will usually increase drug release but not by a constant ratio between drugs. A reversal of an effect is shown by the addition of magnesium stearate, which in some instances increases rather than decreases drug release (its more usual effect). The addition of 1 % sodium lauryl sulphate does not provide a major enhancement of drug release, and in certain cases can be detrimental. There is no consistent order of effectiveness of the three diluents, and thus a universal capsule diluent, which will always improve drug release, does not appear to be a possibility.
Neuromuscular actions of edrophonium in the lateral segmental tail muscle of the rat in vivo
Authors: Whittaker R 
Published: April 2011

Abstract
The actions of edrophonium on neuromuscular transmission in vivo have been studied using the lateral segmental tail muscles of the rat. The drug produced an increase in amplitude of the miniature end-plate potentials (m.e.p.p.s) without an effect on their frequency and increased the amplitude of the end-plate potentials (e.p.p.s) without increasing quantal release of transmitter. It is concluded that the anticholinesterase action of this drug in vivo facilitates neuromuscular transmission, which confirms many of the findings from in vitro studies.
Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate
Authors: Smith M J H , Ford-Hutchinson A W , Elliott P N C 
Published: April 2011

Abstract
Acetylsalicylic acid (aspirin) and sodium salicylate are equally effective in reducing the swelling in the carrageenan-induced paw test and the accumulation of leucocytes into the inflammatory exudate produced by the subcutaneous implantation of polyvinyl sponges in the rat. Aspirin but not sodium salicylate caused a significant reduction in the potentiation of paw oedema found after the concurrent administration of carrageenan and arachidonic acid. Some implications of these findings are discussed.
The evidence of the release of prostaglandin-like material from rabbit kidney and guinea-pig lung by (–)-trans- Δ9-tetrahydrocannabinol
Authors: Kaymakcalan S , Ercan Z S , Türker R K 
Published: April 2011

Abstract
Injection of (–)-trans-Δ9-tetrahydrocannabinol (THC) through the renal artery caused a decrease in perfusion pressure and an increase in urine produced by the isolated perfused rabbit kidney. Both effects of THC are inhibited by the prior addition of aspirin to the perfusion medium. THC also induced a dose-dependent increase in perfusion pressure on the isolated perfused lung of guinea-pig and the effluent from the lung produced a contraction on the isolated continuously superfused rat stomach fundus strip. These effects are prevented by the pretreatment of the lung with aspirin which inhibits the production of prostaglandins (PG) and SC 19220 which inhibits the pharmacological effects of PG.