bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational analysis of dopamine by the INDO molecular orbital method
Authors: Grol Cor J , Rollema Hans 
Published: April 2011

Abstract
The results of INDO calculations on dopamine are reported. A conformational energy map and an isodistance map for the key distances N—OH1, N—OH2 in dopamine as functions of the two main torsion angles τ1 and τ2 were constructed. In addition to the three known minima of dopamine corresponding to the trans and gauche forms, two new minima were found. The key distances of the rigid analogues of dopamine, apomorphine, isoapomorphine, 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene and isoquinoline were plotted on the isodistance map of dopamine. By taking the corresponding τ values as coordinates on the energy map, conformations of dopamine, resembling the rigid analogues, could be found. When a conformation is close to a local minimum it is assumed that this conformation is energetically favourable. The possible relation between the energy minima and the biological action of dopamine is discussed. An explanation is suggested for the lack of dopaminergic activity of isoapomorphine.
Pharmaceutical suspensions: micro electrophoretic properties
Authors: Kayes J B 
Published: April 2011

Abstract
The microelectrophoretic properties of the drugs griseofulvin, betamethasone, nalidixic acid and thiabendazole in aqueous dispersion have been examined and the zeta potentials calculated from the measured mobilities. Variation in magnitude of particle charge with pH of dispersion is reported and related to the chemical structure and surface characteristics. The effect of adding anionic (sodium dodecyl sulphate) cationic (dodecyl trimethyl bromide) and non-ionic (polyoxyethylene glycol monoethers of hexadecanol) surface-active agents, and mixtures of these ionic and non-ionic species, on the electrophoretic properties of the drug dispersions has been measured. The results reported agree with those found previously for a model polystyrene latex suspension system under the same conditions.
Dissolution from tablets prepared using ethyl cellulose microcapsules
Authors: Jalsenjak I , Nicolaidou Constantia F , Nixon J R 
Published: April 2011

Abstract
Microcapsules containing sodium phenobarbitone cores in ethyl cellulose have been used to prepare tablets at from 3·9 to 358·9 MPa compression pressures. The tensile strength of these tablets is related linearly to the core: wall ratio and to the microcapsule size. Dissolution of the drug from the microcapsules is also related to the core: wall ratio and microcapsule size, but except at low compression pressures is almost independent of the pressure used during preparation. The tablet matrix remains intact during the dissolution and the equations developed by Schwartz, Simonelli & Higuchi (1968) are followed. Large microcapsules of 1:2 core:wall ratio produce friable tablets with rapid release of contents.
Caffeine-phenacetin interaction in the rat: effects on absorption, metabolism and locomotor activity
Authors: Collins Catherine , Richards P T , Starmer G A 
Published: April 2011

Abstract
The interactive effects of caffeine and phenacetin on the locomotor activity of the DA rat involved changes in absorption and metabolism as well as effects possibly exerted at the cns level. Phenacetin initially retarded the absorption of caffeine when coadministered by gavage but not when caffeine was given intraperitoneally and phenacetin orally. Phenacetin also increased the time for the plasma/caffeine concentration to peak, increased its peak concentration and prolonged its presence in the plasma. Urinary excretion patterns, suggested a blockade of the N-demethylation of caffeine by phenacetin. In contrast, caffeine had only a minor influence on the absorption and metabolism of phenacetin. The locomotor effects of the caffeine-phenacetin combination reflected the absorptive and metabolic interactions which occurred. Caffeine-induced hyperactivity was initially masked by phenacetin in a dose-dependent manner but after 2 h, when the plasma phenacetin concentrations were much lower, its retarding influence on caffeine metabolism became apparent and hyperactivity consequent upon an elevated plasma caffeine concentration was seen. Phenacetin also antagonized the hyperactive effects of theophylline and of (+)-amphetamine.
The interaction between clonidine and various neuroleptic agents and some benzodiazepine tranquillizers
Authors: van Zwieten P A 
Published: April 2011

Abstract
The central hypotensive action of clonidine, infused into the vertebral artery of chloralose-anaesthetized cats was antagonized by several phenothiazine-neuroleptics (chlorpromazine, promazine, promethazine, thiethylperazine, thioridazine), by chlorprothixene and to a limited extent by haloperidol administered via the same route. Pimozide and some benzodiazepines (chlordiazepoxide, diazepam and flurazepam) hardly influenced the central hypotensive response to clonidine. The antagonism between clonidine and the psychotropic drugs is probably associated with central α-adrenoceptors, clonidine being the agonist and the neuroleptic agents the antagonists at these receptors. Virtually the same type of antagonism was observed in conscious, spontaneously hypertensive rats where both clonidine and the neuroleptic drugs were injected intravenously. The phenothiazines and also piperoxane effectively diminished the centrally induced hypotensive response to clonidine, whereas the initial pressor effect to clonidine was not reduced.
Stereoselective drug distribution and anticoagulant potency of the enantiomers of phenprocoumon in rats
Authors: Schmidt W , Jähnchen E 
Published: April 2011

Abstract
The elimination, distribution and anticoagulant activity of S(—)-, R(+)-, and R,S(±)-phenprocoumon were determined in male Wistar-Lewis rats after intravenous injection of a single dose of 0·6 mg kg−1. From the plasma concentrations which elicited the same anticoagulant effect, S(—)-phenprocoumon was 4 to 5 times more potent than R(+)-phenprocoumon. The potency of the racemate was between those of the enantiomers. The mean biologic half-life of the S(—)-enantiomer was shorter (12·5 h) than that of R(+)-phenprocoumon (17·8 h). No differences were observed in the apparent volume of distribution. However, the mean liver: plasma concentration ratio was higher for the S(—)-(6·9) than for the R(+)-enantiomer (5·2). At a total concentration of 16·8 μg ml−1 the percentage of unbound drug in rat serum was significantly higher for the S(—)- (1·13%) than that for the R(+)-enantiomer (0·76%). Values obtained for the racemate were always between those of the enantiomers. It is concluded that stereoselective differences in the distribution between plasma and liver, and consequently in the rate of elimination are most likely due to stereoselective differences in serum protein binding. The greater anticoagulant potency of the S(—)- over the R(+)-enantiomer, cannot be explained primarily by the observed pharmacokinetic differences.
The effects of prostaglandins E1, E2, F1α and F2α on guinea-pig ileal and colonic peristalsis
Authors: Eley Kenneth G , Bennett Alan , Stockley Helen L 
Published: April 2011

Abstract
Prostaglandins (PGE1, E2, F1α and F2α) have been tested on the peristaltic reflex in isolated segments of guinea-pig ileum and colon using simultaneous recordings of fluid propulsion and longitudinal and circular muscle activity. Propulsion and circular muscle peristaltic activity were increased by serosally applied PGF compounds in the ileum and PGE or PGF compounds in the colon following initial contraction of the longitudinal muscle. This is consistent with a role for prostaglandins in peristalsis. Mucosally applied PGF compounds had no significant effect.
Application of orthogonal functions to the spectrophotometric determination of phenytoin in pharmaceutical preparations
Authors: Amer M M , Ahmed A K S , Hassan S M 
Published: April 2011

Abstract
A simple ultraviolet spectrophotometric method for the determination of phenytoin in pharmaceutical preparations has been developed. The mean was 100·9% (6 determinations) and the coefficient of variation was 1·2%. The method was applied successfully to the determination of phenytoin in capsules and suspensions.
The influence of additives on the presentation of a drug in hard gelatin capsules
Authors: Newton J M , Razzo F N 
Published: April 2011

Abstract
The influence of the concentration of lactose, magnesium stearate and sodium lauryl sulphate on the in vitro dissolution and the drug content of hard gelatin capsules filled under conditions which result in a maximum tapped bulk density, has been evaluated by a factorially-designed experiment. The 3 factors have a significant effect on both drug release and capsule filling. Interactions between the 3 factors, however, limit the exact quantification of the magnitude of their influence by a simple linear model. A quadratic relation, when only 2 factors are considered, can be used to provide a prediction of the influence of these factors. The relations between 2 factors are demonstrated as contours of equal in vitro drug release and equal drug content of capsule, at constant concentrations of the third factor. The contours show the important influence of lactose concentration on drug release and capsule filling, and the large changes in response which can occur by the addition of a third factor. They also provide a clear guide to the formulation of hard gelatin capsules.
Autoxidation of N-hydroxyphenylalkylamines: the inhibitory effect of some anions on copper catalysed autoxidation of N-hydroxyphentermine
Authors: Jonsson Ulf , Lundkvist Gunilla , Eriksson Sven O , Lindeke Björn 
Published: April 2011

Abstract
The inhibitory effect of certain electrolytes and buffers on the copper catalysed autoxidation of N-hydroxyphentermine (2-hydroxylamino-2-methyl-1-phenylpropane) has been investigated. The presence of ions such as SO42−, Cl− or Br− markedly reduced the rate of oxidation. Phosphate and carbonate buffers had a similar effect with halides and phosphate buffers being the most inhibitory. The occurrence of 2-methyl-2-nitro-1-phenylpropane and 2-methyl-1-phenylpropene-(1) as secondary oxidation products was also established.
Binder distribution onto binary mixtures of glass spheres
Authors: Dingwall D , Ismail S I 
Published: April 2011

Abstract
Glass spheres (0·8 and 0·4 cm diam.) in differing weight ratios were treated in a rotating pan with four pharmaceutical binder fluids. Binder uptake for a sphere of 1 g was greater onto the smaller spheres irrespective of binder or wt ratio used. There were differences in uniformity of uptake, the solution binders (PVP and gelatin) being more evenly distributed than the mucilaginous binders (starch and methylcellulose). Binder distribution on the basis of unit surface area showed less obvious differences between the sphere sizes. Possible consequences of such binder distribution through powder aggregates are discussed.
Permeation of oestrone, oestradiol, oestriol and dexamethasone across cellulose acetate membrane
Authors: Barry B W , Brace A R 
Published: April 2011

Abstract
The permeation across cellulose acetate of three oestrogens, differing only in the number of hydroxyl groups attached to the nucleus, and a ‘standard’ steroid, dexamethasone, was investigated using the lag-time method for calculating diffusion parameters, between 10 and 40°. Diffusion coefficients for the similarly-sized oestrogens were relatively insensitive to marked changes in polarity, but increased permeation was correlated with increased partition coefficients, decreased polarity and fewer hydroxyl groups on the nucleus. Permeation increased with temperature and energies of activation were calculated from Arrhenius-type plots. Ep values ranged from 4·84 k cal mol−1 (20 kJ mol−1) for the least polar steroid (oestrone) to 6·91 k cal mol−1 (29 kJ mol−1) for the most polar steroid (oestriol). The results implied that steroid diffusion occurred through aqueous membrane channels, but that it was impeded to various extents by both obstruction and polar interaction effects.
The effect of tris buffers on rat liver mitochondrial monoamine oxidase
Authors: Fowler C J , Callingham B A , Houslay M D 
Published: April 2011

Abstract
The effect of tris buffers upon the monoamine oxidase (MAO) activity in rat liver mitochondria has been investigated. Tris buffer was shown to inhibit MAO in a non-competitive manner with a Ki of 15–25 mm. Tyramine, 5-hydroxytryptamine and β-phenethylamine but not benzylamine oxidations were all inhibited by tris buffer. All inhibitions, except that of 5-HT, were completely reversible. It is suggested that these effects are produced by conformational changes in the structure of the MAO. The significance of these results is discussed with respect to the use of tris buffers in the extraction and estimation of the activity of MAO.
The effects of diethylcarbamazine citrate on smooth muscle
Authors: Abaitey A K , Parratt J R 
Published: April 2011

Abstract
The effect of the anthelmintic drug diethylcarbamazine citrate (DECC) was examined on the guinea-pig isolated ileum, rabbit duodenum, chick oesophagus, rat portal vein and pig coronary artery. DECC contracted all the gastrointestinal smooth muscle preparations. The contractions were antagonized by hexamethonium and atropine but they were not affected by mepyramine or methysergide in concentrations that abolished, or markedly reduced, responses to histamine and 5-hydroxytryptamine. DECC inhibited the responses of the guinea-pig ileum to other spasmogens, namely, acetylcholine, histamine and nicotine. Physostigmine markedly potentiated the responses of the chick oesophagus and the rabbit duodenum to DECC. DECC relaxed the potassium chloride-induced contractions of the pig coronary artery strips; these relaxations were not modified by propranolol or calcium chloride. There was no evidence that DECC released histamine from skin or muscle.
The extraction and analysis of benzodiazepines in tissues by enzymic digestion and high-performance liquid chromatography
Authors: Osselton M D , Hammond M D , Twitchett P J 
Published: April 2011

Abstract
A simple, rapid and sensitive method is described for the analysis of unchanged benzodiazepine drugs and their metabolites, in human and animal tissues, using the proteolytic enzyme subtilisin Carlsberg followed by reverse-phase liquid chromatography. The enzymic digestion yields far higher recoveries than conventional extraction methods, while the liquid chromatographic analysis allows the rapid separation and detection of nanogram quantities of these drugs without the need for elaborate “clean-up” procedures.
Weight and activity in male mice after daily inhalation of cannabis smoke in an automated smoke exposure chamber
Authors: Weinberg A D , Dimen E , Borzelleca J F , Harris L S 
Published: April 2011

Abstract
An automatic smoking machine capable of delivering marihuana smoke to groups of 10 mice at a time at a constant concentration of Δ9-THC is described. In all cases the flow rate (50 ml s−1 or 100 ml s-1) of a smoke: air mixture, and the dilution factor (1:20 or 1:10 smoke:air) was adjusted to give the same equilibrium concentration of Δ9-THC in the chamber atmosphere. At a concentration of 0–123 mg Δ9-THC litre−1 of exposure chamber atmosphere (1:20 smoke: air; 100 ml s−1 flow rate), a seven day schedule of 20 min daily treatments significantly decreased activity of the marihuana-treated animals by the sixth day over both air and placebo smoke controls. This concentration and exposure schedule failed to affect weight gain during this same period. A significant decrease in activity, although not as great as in the marihuana-treated group, was also seen in the placebo control group compared with the air control animals, indicating the need for a smoke control group in all experiments involving the administration of marihuana via inhalation. An exposure period of 102 min, with marihuana smoke diluted with air 1:10 (50 ml s-1 flow rate), at the same equilibrium concentration of 0·123 mg Δ9-THC litre−1, resulted in a mortality of 90% following administration or within 48 h. 102 min of exposure to an atmosphere of placebo smoke at a smoke:air dilution of 1:10 (50 ml s-1 flow rate), resulted in no mortality.
Identification of di- and tri-substituted hydroxy and ketone metabolites of Δ1-tetrahydrocannabinol in mouse liver
Authors: Harvey D J , Martin B R , Paton W D M 
Published: April 2011

Abstract
In vivo liver metabolites of Δ1-tetrahydrocannabinol (Δ1-THC) were examined with a gas chromatograph—mass spectrometer—computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2“,7-, 3”,7-, and 6β,7-dihydroxy-Δ1-THC; 2“,6α,7-, and 3”,6α,7-trihydroxy-Δ1-THC; 2“-, 3”-, and 7-hydroxy-6-oxo-Δ1-THC, and 2“,7- and 3”,7-dihydroxy-6-oxo-Δ1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.
Dilute solution properties of clindamycin 2-palmitate hydrochloride
Authors: Abbott Teresa I , Benton D P , Hampson C A 
Published: April 2011

Abstract
Clindamycin 2-palmitate hydrochloride forms micelles in aqueous solution at concentrations above 2·2 times 10−3 m. Dilution of micellar solutions of the drug to concentrations less than 2·0 times 10−3 m produces turbid systems. Turbidity is caused by unionized drug, produced by hydrolysis of the salt, phasing out of solution at concentrations too low for micelles to be formed. Changes in specific conductivity and turbidity associated with the phasing-out process have been measured and explained in terms of the rates of the various processes involved, including demicellization and emulsion stability. The phenomenon of phasing-out, below a critical concentration in aqueous solution, is predicted to be a general one for weakly ionized surfactants where the unionized species possesses low water solubility.
Effect of two non tricyclic antidepressant drugs on [14C]5-hydroxytryptamine uptake by rat platelets
Authors: Wielosz Marian , Dall'Olio Alberto , de Gaetano Giovanni , Garattini Silvio 
Published: April 2011

Abstract
The uptake of 14C-5-HT by rat blood platelets was examined in vitro in experimental conditions which allowed measurement of the initial velocity and excluded other passive processes across the cell membrane. In these conditions, the effect of two non tricyclic antidepressant drugs (Lilly 110140 and trazodone) was investigated. Lilly 110140 was as active as chlorimipramine and several times more active than imipramine as an inhibitor of 14C-5-HT uptake. Like chlorimipramine, Lilly 110140 appeared to be either a non-competitive or an uncompetitive inhibitor, according to the concentration of drug used. Trazodone also inhibited 14C-5-HT uptake by platelets but to a lesser extent than chlorimipramine, imipramine or Lilly 110140. m-Chlorophenylpiperazine, a possible metabolite of trazodone, was about 3 times more potent an inhibitor than the parent molecule. Both compounds acted non-competitively. Compared with published data on the effect of Lilly 110140 and trazodone on brain 5-HT, the present results support the suggestion that rat platelets are a useful pharmacological model of serotoninergic nerve endings.
Biochemical and pharmacological studies on amineptine (S 1694) and (+)-amphetamine in the rat
Authors: Samanin R , Jori A , Bernasconi S , Morpugo E , Garattini S 
Published: April 2011

Abstract
The pharmacological activities of amineptine (S 1694) and (+)-amphetamine and their interaction with biogenic amines have been examined in rats. The locomotor activity, stereotyped behaviour and hypothermia induced by amineptine were similar to but not as marked as those produced by (+)-amphetamine, and there was little or no anorectic action. Amineptine does not modify the concentrations of brain noradrenaline or acetylcholine which are respectively reduced and increased by (+)-amphetamine. Moreover, amineptine does not affect significantly the decrease of brain noradrenaline induced by an intraventricular injection of 6-hydroxydopamine, an effect significantly antagonized by (+)-amphetamine. On the other hand, like amphetamine, amineptine significantly reduces the effect of 6-hydroxydopamine on brain dopamine. Both drugs increase the striatal concentrations of homovanillic acid and show a cross tolerance in this action. Therefore they could act similarly on the striatal dopaminergine system. Amineptine thus appears to be a new type of antidepressant with a brain biochemical profile differing from that of other drugs used in depressive disorders.
Plasma concentrations and excretion of zipeprol in man under acidic urine conditions
Authors: Beckett A H , Achari R 
Published: April 2011

Abstract
Plasma concentrations of zipeprol, and the urinary excretion of it and two of its basic metabolites, compound II and compound III were examined after oral administration of zipeprol hydrochloride to man. The drug was rapidly and extensively metabolized, and the amount of unchanged drug excreted in the acidic urine varied from 1–5% of the dose; the two basic metabolites accounted for 19–38% of the dose.
Evidence from agonist and antagonist studies to suggest that the β1-adrenoceptors subserving the positive inotropic and chronotropic responses of the heart do not belong to two separate subgroups
Authors: Lumley P , Broadley K J 
Published: April 2011

Abstract
The positive inotropic and chronotropic responses of guinea-pig isolated left and right atria to 17 sympathomimetic amines were examined under conditions selected to control the pharmacological environment. Each agonist was compared with (-)-isoprenaline as the reference by constructing dose-response curves. Equiactive molar concentration ratios relative to (-)-isoprenaline were calculated at the EC50 for rate and tension responses. Statistical analysis revealed that (-)-noradrenaline and (±)-α-methylnoradrenaline were tension selective whereas (±)-α-ethylisoprenaline and N-methyldopamine were rate selective relative to (-)-isoprenaline. However, no structural trends emerged. The rank order of potency varied slightly between rate and tension, but an analysis of the regression and correlation coefficients indicated respectively that the equiactive molar concentration ratios and the rank orders could be considered identical on rate and tension. Antagonism of the (-)-isoprenaline-induced rate and tension responses by acebutolol, atenolol, practolol and propranolol was assessed from the pA2 values which were almost identical for both parameters with each antagonist. It is concluded that the β1-adrenoceptors mediating the positive inotropic and chronotropic responses do not warrant subdivision into two separate groups.