bluuebunny/crossref_metadata_2025_split huggingface dataset:
The α-adrenoceptor blocking effect of indoramin on human isolated smooth muscle
Authors: Variava Dinaz H , Turner Paul 
Published: April 2011

Abstract
The pharmacological effects of indoramin, a new hypotensive drug, were studied on human isolated smooth muscle preparations. Indoramin was shown to have a potent α-adrenoceptor blocking activity on specimens of colon, ileum and vein. The blockade fulfilled the established criteria for competitive antagonism of noradrenaline. The mean pA2 values were 6&#x006d;̇57 for the circular muscle of the colon, 6&#x006d;̇91 for longitudinal muscle of the colon, 6&#x006d;̇64 for longitudinal muscle of the ileum and 6&#x006d;̇58 for saphenous vein. Indoramin (10−3m) did not reduce acetylcholine-induced contractions of the longitudinal muscle of the colon and ileum.
Influence of electrolytes on the hydration of methylcellulose in solution
Authors: Marriott P H , John E G 
Published: April 2011

Abstract
Light-scattering techniques were used to obtain weight-average molecular weights for three grades of methylcellulose in water. On addition of electrolyte to the polymer solutions the molecular weight was not found to alter but the root-mean-square end-to-end length decreased. This contrasts with the results of Neely (1963). The exponent α of the Mark-Houwink viscosity equation was also found to decrease in the presence of electrolyte. Two stages of polymer dehydration are suggested for non-ionic cellulose ether derivatives.
The formulation and sterilization of a surgical lubricant gel based on carboxypolymethylene
Authors: Adams Isobel , Davis Stanley S 
Published: April 2011

Abstract
A lubricant gel of optimal consistency containing a local anaesthetic (lignocaine) has been formulated which can be sterilized by gamma irradiation. A rheological specification was obtained by examination of some currently used preparations. The variation in their consistency was large but all exhibited pseudoplastic flow with a yield value. Gels based on tragacanth, the methylcelluloses and the Carbopols were suitable as lubricants before sterilization and after autoclaving, but on gamma irradiation the gel structure was destroyed. Ethanol (5–10%) protected the Carbopol formulations. Irradiation of lignocaine solutions caused some cloudiness and a small drop in pH. Ethanol and metabisulphite acted as protective agents. A final formulation was developed consisting of a Carbopol gel (1%) neutralized by lignocaine base (2%) and the biological availability of the local anaesthetic was assessed using an in vitro method.
Inhibition of human platelet 5-hydroxytryptamine uptake by ß-phenethylamine derivatives
Authors: Richter Anna , Smith S E 
Published: April 2011

Abstract
Forty-eight derivatives of ß-phenethylamine have been studied as inhibitors of 5-hydroxytryptamine uptake by human blood platelets in vitro. Inhibitory potency was found to be increased by para-substitution with electronegative groups, by α-methylation in the D-configuration and by addition of N-alkyl groups, and to be reduced by saturation of the ring, by ortho-methoxylation, meta- or ß-hydroxylation and by hydrazine formation. It is suggested that optimal affinity involves folding of the molecule to fit a cleft-like carrier site. The structural requirements for activity show features of similarity to those of tryptamine and tricyclic antidepressant derivatives and some resemblance with requirements for inhibition of the adrenergic uptake1 mechanism of the heart. No obvious correlation exists between the activity of these drugs as inhibitors of platelet 5-HT uptake and their ability to exert effects thought to involve central tryptaminergic mechanisms.
Effect of acute and chronic treatment with practolol on cardiovascular responses in the pithed rat
Authors: Lewis M J 
Published: April 2011

Abstract
Chronic administration of practolol to the pithed rat produced a reduction in the pressor responses to electrical stimulation of the spinal cord and potentiation of pressor responses to high doses of (—)-noradrenaline compared to control animals. Acute administration of practolol caused an increase in the pressor responses to both electrical stimulation and high doses of noradrenaline. Heart rate responses to both forms of stimulation were less than control values after both acute and chronic dosage with practolol. It is possible that practolol reduces the release of noradrenaline at the sympathetic nerve ending after chronic administration.
A molecular orbital study of tissue selectivity in ß-adrenoceptor blocking agents
Authors: Germer Henry A 
Published: April 2011

Abstract
A molecular orbital study has been made on a group of eight ß-adrenoceptor blocking agents using CNDO/2 type calculations. Of the group, two are relatively selective for cardiac receptors, two for vascular receptors and four are non-selective. Comparison of the net charges on the ß-hydroxyl group oxygens and onium group nitrogens, as well as the O-N distances, reveals small differences. In the traditional view of adrenoceptor agent molecular geometry, the onium group and the aromatic part of the molecule are near the trans-configuration for the low energy conformation of all eight molecules. However, when the relation of a primary side chain feature, such as the O-N axis, and the plane of the aromatic ring is examined, noticeable steric differences between the various agents are evident.
Aggregation of antihistamines in aqueous solution: micellar properties of some diphenylmethane derivatives
Authors: Attwood D , Udeala O K 
Published: April 2011

Abstract
The micellar properties of the antihistamine drugs, diphenhydramine hydrochloride, bromodiphenhydramine hydrochloride, chlorcyclizine hydrochloride and diphenylpyraline hydrochloride, have been studied in aqueous solution. The zeta potentials of the micelles were calculated from their electrophoretic mobilities as determined by a dye-tracer technique. Estimates of the degree of ionization of the micelles using a combination of conductivity and electrophoresis data were in reasonable agreement with values previously determined by light scattering. The extent of micellar hydration has been calculated from viscosity data. The hydrophobic and electrical contributions to the free energy of micellization have been calculated and related to the chemical structure.
Neuromuscular and other blocking actions of a new series of mono and bisquaternary aza steroids
Authors: Gandiha A , Marshall I G , Paul Dharam , Singh Harkishan 
Published: April 2011

Abstract
The effects of a newly-synthesized series of mono and bisquaternary aza steroids have been investigated in the anaesthetized cat. All the compounds have been tested for neuromuscular blocking, ganglion blocking and vagolytic activity. The monoquaternary compounds of the series were weak neuromuscular blocking agents, their main action being to produce ganglion blockade and a fall in blood pressure. Both the bisquaternary compounds of the series primarily exhibited neuromuscular blocking activity of short duration and rapid onset. 4-Methyl-17 β-dimethylamino-4-aza-5α-androstane dimethiodide (HS-467) was approximately equipotent with tubocurarine as a neuromuscular blocking agent, whereas 17a-methyl-3β-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide (HS-310, chandonium iodide) was 4–5 times more active. Both compounds exhibited extremely weak ganglion blocking activity. Structure-activity relations are discussed, and it is concluded that in this series two quaternary heads are necessary for optimal neuromuscular blocking activity. The possibility that in the bisquaternary compounds interonium distance, or stereochemical conformation may be the main factor in determining specific neuromuscular blocking activity is discussed.
The effects of a human plasma fraction on carrageenan-induced paw oedema in the rat
Authors: Ford-Hutchinson A W , Elliott P N C , Bolam J P , Smith M J H 
Published: April 2011

Abstract
A fraction isolated from normal human plasma inhibits the swelling of carrageenan-induced paw oedema in the rat when given as a single intravenous injection at time intervals up to 24 h before and up to 3 h after the administration of the carrageenan. Repeated doses of the fraction cause a delay in the development of the paw oedema.
Powder mixing in the tableting of fenfluramine hydrochloride; evaluation of a mixer
Authors: Cook P , Hersey J A 
Published: April 2011

Abstract
A vertical cone mixer has been used to mix a single active component, fenfluramine hydrochloride, with a number of diluents used for production batch-scale tablet preparation. The mixing operation was followed by the analysis of fenfluramine hydrochloride in a number of samples equivalent to the final tablet size. The results may be suitably analysed by treating the diluent materials as a single component in a binary mixture.
Application of orthogonal functions to spectrophotometric analysis. The combined polynomial method
Authors: Wahbi A M , Ebel S 
Published: April 2011

Abstract
A general method is outlined for the linear combination of orthogonal polynomials belonging to one group of points to eliminate interferences in spectrophotometric analysis. The method is particularly useful when it is difficult to find a set of wavelengths over which the coefficient of the irrelevant absorption is negligibly small relative to the assay coefficient. The method is illustrated by the determination of salicylamide in the presence of chloroquine.
“First-pass” metabolism of paracetamol in rat liver
Authors: Cohen Gerald M , Bakke Olav M , Davies Donald S 
Published: April 2011

Abstract
Paracetamol was administered intraperitoneally or intravenously to male rats. Its ‘availability’ in the systemic circulation after intraperitoneal administration was only 34% of that after intravenous administration. This suggested a high “first-pass” metabolism of intraperitoneally administered drug, which was confirmed using the rat isolated perfused liver. The hepatic extraction ratio for paracetamol decreased with increasing concentrations of the drug in the perfusion fluid, suggesting that gastric emptying rate, by controlling the concentration of drug in the portal vein, could influence the amount of “first-pass” metabolism.
Detection, isolation and characterization of normorphine and norcodeine as morphine metabolites in man
Authors: Boerner Udo , Roe Robert L , Becker Charles E 
Published: April 2011

Abstract
Normorphine and norcodeine were identified by two-dimensional thin-layer chromatography (t.l.c.) as human urinary morphine metabolites from 24 h urine samples of three patients who had received 190–210 mg morphine sulphate intravenously and from one patient who had chronically received 220 mg morphine sulphate orally per day. Both metabolites were isolated by preparative t.l.c. Comparison of the isolated norcodeine and normorphine with their respective authentic compounds, prepared by chemical synthesis, showed identical melting points, mass fractionation patterns, and chemical ionization spectra, confirming t.l.c. identification.
Histamine, 5-hydroxytryptamine, kinins and the anti-inflammatory activity of human plasma fraction in carrageenan-induced paw oedema in the rat
Authors: Bolam J P , Elliott P N C , Ford-Hutchinson A W , Smith M J H 
Published: April 2011

Abstract
In the carrageenan-induced paw oedema reaction in the rat, the swelling and accumulation of [131I]albumin showed a similar time course over 4 h. Both aspects of the oedema were inhibited by a fraction prepared from human plasma. Treatment of the animals with substances which either deplete the levels or antagonize the actions of either histamine, 5-hydroxytryptamine or kinins showed that these mediators are concerned in the development of rat paw oedema after the injection of either carrageenan or yeast but not with the anti-inflammatory action of the plasma fraction.
Structural effects in drug distribution: whole animal pharmacokinetics
Authors: Notari Robert E , Burkman A M , van Tyle W Kent 
Published: April 2011

Abstract
Computer-generated data simulating the results of assays of homogenized whole animals as a function of time following rapid intravenous injection have been employed to calculate various pharmacokinetic constants in both one and two compartment open models. The results have been compared to those obtained with data representing analysis of blood samples at identical time intervals. Data for whole animal analysis are equally reliable in calculating the first-order constants for distribution and elimination when applied to the appropriate cases. However, the range of utility is smaller when the whole animal method is used. The whole animal approach does offer some unique advantages over the classical plasma data method and these are discussed. The range of utility and the method for calculating pharmacokinetic rate constants from whole animal data are clearly defined.
Structural effects in drug distribution: comparative pharmacokinetics of apomorphine analogues
Authors: Burkman A M , Notari Robert E , van Tyle W Kent 
Published: April 2011

Abstract
A two compartment open model, modified to include brain as a third compartment, was found to describe the pharmacokinetics of three aporphines in mice. Data include whole animal analysis, brain analysis and evaluation of stereotypical gnawing behaviour. The relative potencies of the derivatives, based upon brain content, were found to be apomorphine = 1, norapomorphine = 0·06 and N-n-propylnorapomorphine = 0·39. The potency of the N-n-propyl analogue is less than that previously reported on an intraperitoneal (i.p.) dosage basis (1·14). The ability to distribute into the brain, based on the entire time course for drug in that compartment, appears to be N-n-propylnorapomorphine &gt;apomorphine &gt;norapomorphine. The values for t 1/2 in mice are 29 min for the N-n-propyl derivative, 20 min for norapomorphine and 47 min for apomorphine which was previously reported to be 8·5 min based upon the inappropriate assumption of a one compartment model. The successful pharmacokinetic analysis was combined with the evaluation of structural effects on drug distribution and its resultant influence on pharmacokinetic response for the three closely related derivatives to demonstrate the applicability of the previously described whole animal pharmacokinetic treatment (Notari, Burkman & Van Tyle, 1974).
A general method of determining the first order input rate constant of a drug that is directly absorbed into the central compartment
Authors: Vaughan D P , Mallard D J H , Mitchard M 
Published: April 2011

Abstract
A simple equation by which the first order rate constant for the absorption of a drug into the central compartment of any linear mammillary pharmacokinetic model can be calculated is presented. No specific knowledge of the distribution or elimination characteristics of the drug is required.
The influence of phospholipids on the transport of antibacterial agents across non-aqueous barriers, and the methods used to quantitate the rate processes
Authors: Padfield John M , Kellaway I W 
Published: April 2011

Abstract
Penicillin G and ampicillin are known to bind with phospholipids, which may influence antibiotic transport across the bacterial cell wall. This influence has been investigated in vitro in a three-phase cell containing 1-octanol as the non-aqueous barrier. The data have been analysed by an iterative technique using digital computation, in order to quantitate the rate processes. The results indicate that binding of the antibiotics with phospholipids occurs at the oil-water interface which influences the further transport of the antibiotics through the non-aqueous phase. The possible biological significance is discussed.
Assignment of configuration to 2î-hydroxy-2-methyl-9-hydroxy-5,9-dialkyl-6, 7-benzomorphans using mass spectrometry
Authors: Vaughan D P , Hill M , Mitchard M 
Published: April 2011

Abstract
The configuration and structure of α- and β-2î-hydroxy-2-methyl-9-hydroxy-5,9-dialkyl-6,7-benzomorphans have been determined by mass spectrometry.
A useful transformation for comparing dose-response curves
Authors: MacKay D , Wheeler J 
Published: April 2011

Abstract
Several mathematical equations have been tested for their ability to fit pharmacological dose-response curves over the range 5 to 95% of the maximal response. It has been shown that one such equation, which will be called the L-transformation, adequately fits sets of dose-response data obtained from a number of different tissues. The graphical application of this equation has been suggested previously by other workers but has been used only to a very limited extent.
Techniques have now been developed which enable the L-transformation to be fitted to single sets of dose-response data, and to pairs of sets of data simultaneously. By itself the L-transformation cannot adequately fit all dose-response curves. However if another preliminary transformation is carried out on the measured responses then the L-transformation can usefully be applied to dose-response curves of widely different shapes and slopes. Various applications of these techniques are discussed. When the L-transformation is applied to pairs of dose-response curves obtained, for example, from a single piece of isolated tissue, it can be used to calculate potency ratios, with standard errors and fiducial limits. When combined with the occupation theory of drug action and use of the null method, the L-transformation can be applied to suitable pairs of dose-response curves to provide estimates of the affinity constants (with their standard errors) of drugs for their receptors. The techniques can be extended to other models of drug-receptor interaction. Computer programs are available which greatly facilitate the application of these curve fitting methods to the types of problem outlined above.
Effect of neuroleptics on the disappearance rate of [14C] labelled catecholamines formed from [14C]tyrosine in mouse brain
Authors: Hyttel John 
Published: April 2011

Abstract
The accumulation and disappearance of [14C] labelled dopamine and noradrenaline formed from [14C]tyrosine in mouse brain has been investigated. After reaching peak concentrations the [14C]dopamine and noradrenaline concentration declined exponentially with half-lives of 2·5 and 6·7 h respectively. The effect of some known neuroleptics belonging to different chemical groups as well as of a new neuroleptic compound, Lu 10–022 [2-trifluormethyl-6-fluoro-9-(3-(4-(2-hydroxyethyl) piperazin-l-yl)propyl) thioxanthen], on the disappearance rate of [14C]catecholamines between 1·5 and 3 h after administration of [14C]tyrosine was compared. All neuroleptics tested, except clozapine, increased the disappearance rate of [14C]dopamine in a dose-dependent manner at the lower dose intervals. However, above a certain dose the disappearance rate was not elevated further. Halo-peridol, fluphenazine and Lu 10–022 increased the disappearance of [14C]dopamine more strongly than the rest of the neuroleptics. The disappearance rate of [14C]noradrenaline was also increased by all the neuroleptics, except clopenthixol, although the change was less than for [14C] dopamine disappearance, resulting in a rather poor dose-response relation. Pimozide and Lu 10–022 influenced the [14C] noradrenaline disappearance less than the other neuroleptics. The hypothermic effect caused by the neuroleptics was not related to the change in the disappearance rate of the catecholamines.
Hypothermic and toxic actions of 2–butyne-1, 4-diol and other related diols in the rat
Authors: Taberner P V , Pearce M J 
Published: April 2011

Abstract
The effects of 2-butyne-1,4-diol (BYDL) and related congeners on the body temperature of the rat have been determined. BYDL, at doses above 0·4 mmol kg−1 intraperitoneally, produced a significant fall in body temperature which was dose dependent. 2-butene-1,4-diol (BEDL) had no hypothermic action, and butane-1,4-diol (BDL) produced only a moderate fall in temperature (1·9°) which correlated with the time course of the hypnotic effect of the drug. γ-Butyrolac-tone (GBL), γ-hydroxybutyric acid (GHB) and pentobarbitone at hypnotic doses had similar hypothermic actions which correlated with the period of hypnosis. The hypothermia produced by BYDL could not be prevented by pretreatment with scopolamine or by maintaining the rats at high environmental temperature (32°). BYDL was far more toxic than the other diols examined (LD50 = 0·609-0·635 mmol kg−1 compared to BEDL: 3·71-3·74 mmol kg−1 and BDL: 11·87-11·90 mmol kg−1). Pretreatment of rats with pyrazole, an inhibitor of liver alcohol dehydrogenase, prevented the toxic and hypothermic actions of BYDL. From earlier studies with pyrazole and BDL it was concluded that BYDL itself was not active but that it was possibly converted in vivo by liver alcohol dehydrogenase to a toxic metabolite.
Inhibition of α-chymotrypsin by dibenamine
Authors: Shabibi H al , Smith H J 
Published: April 2011

Abstract
α-Chymotrypsin is rapidly inhibited by an acid solution of dibenamine in an irreversible manner when the reactants are mixed in a buffer at near neutral pH. The degree of inhibition depends on the molar ratio of the reactants. The alkylating species is probably the ethyl-eniminium ion from dibenamine, this ion being present at a higher level in the acid media than in the near neutral media used here.
The difference in activity between (+)- and (-)-methadone is intrinsic and not due to a difference in metabolism
Authors: Sullivan Hugh R , Due Susan L , McMahon Robert E 
Published: April 2011

Abstract
The disposition and metabolism of (+)- and (-)-methadone has been compared in rats. At equal molecular doses, somewhat higher plasma levels of (-)-isomer were observed. At equal analgesic doses, brain and plasma concentrations of (+)-methadone were at least 25 times greater than those of (-)-methadone. No qualitative differences were observed between isomers with respect to in vivo metabolic pattern or in vitro N-demethylation rates. The results strongly support the conclusion that the large differences in analgesic potency between the isomers is due to an intrinsic difference in pharmacologic properties and is not related to a difference in disposition or metabolism.
The surface activity of some antihistamines at the air-solution interface
Authors: Attwood D , Udeala O K 
Published: April 2011

Abstract
The surface activity of some antihistamines at the air-solution interface has been examined. Change of the counterion associated with the drug from chloride to maleate or chloro-theophyllinate considerably decreased the critical micelle concentration and increased the surface activity. The effect on surface activity of changes in the nature of the hydrophobic and hydrophilic groups have also been evaluated.
Narcotic agonist and antagonist potencies of a homologous series of N-alkyl-norketobemidones measured by the guinea-pig ileum and mouse vas deferens methods
Authors: Kosterlitz H W , Leslie Frances M , Waterfield Angela A 
Published: April 2011

Abstract
The narcotic agonist and antagonist potencies of the series of N-alkyl-norketobemidones from norketobemidone to decylnorketo-bemidone have been determined. The values obtained in the electrically stimulated preparations of the guinea-pig ileum and the mouse vas deferens are closely correlated. The agonist potencies observed in the guinea-pig ileum agree well with those found in the mouse hot-plate test (Oh-ishi & May) and those obtained by determining the inhibition of naloxone binding in brain homogenates (Wilson, Rogers, Pert & Snyder). The antagonist potencies in the guinea-pig ileum and, to a lesser extent, those in the mouse vas deferens agree with the values obtained in the morphine-dependent monkey.