bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of treatment and of withdrawal of treatment with guanfacine and clonidine on blood pressure and heart rate in normotensive and renal hypertensive rats
Authors: Salzmann R 
Published: April 2011

Abstract
Disagreement in the literature about the occurrence of rebound hypertension (hypertensive overshoot) in animal models initiated this investigation. Oral doses of clonidine (0.03 mg kg−1) or guanfacine (0.3 mg kg−1) were administered twice daily during three weeks to groups of normotensive and renal hypertensive rats. Blood pressure and heart rate were measured immediately before and 3 h after the first daily dose, and compared with values obtained from placebo-treated control rats. Treatment with either drug induced large daily fluctuations rather than sustained falls in blood pressure. In the normotensive, but not in the hypertensive groups, the morning blood pressures measured before the first daily dose were significantly elevated over those of the control groups after 9 and 5 days of treatment with clonidine or guanfacine. This elevation persisted for 3 days after drug withdrawal. It is concluded that in the rat the duration of action of both drugs was short, so that twice daily administration of both drugs similarly produced large daily fluctuations rather than sustained falls in blood pressure. Blood pressure rises developed during treatment rather than after withdrawal in normotensive rats only. Therefore, this type of study does not relate well to the human situation and different experimental approaches to this problem are needed.
Effect of naloxone on the sensitivity of the vas deferens to various agonists
Authors: Ramaswamy S , Nazimudeen S K , Kameswaran L 
Published: April 2011

Abstract
The effect of naloxone in vitro, on noradrenaline (NA)-induced responses in guinea-pig isolated vas deferens was studied. The responses of NA were potentiated by naloxone (3 μm). It potentiated the responses to methoxamine which has least affinity for uptake sites. Responses induced by acetylcholine and potassium chloride were also potentiated by naloxone. Low calcium (0.8 mM) in the medium antagonized the potentiating action of naloxone. It is suggested that naloxone produces non-specific potentiation, by promoting calcium influx at the post-synaptic site.
More acidic metabolites of Δ1-tetrahydrocannabinol isolated from rabbit urine
Authors: Nordqvist Marianne , Agurell Stig , Rydberg Maria , Falk Lena , Ryman Torsten 
Published: April 2011

Abstract
The in vivo metabolism of Δ1-trahydrocannabinol (Δ1-THC) was further investigated in the rabbit after i.v. administration. Nine acidic metabolites were isolated from a previously not investigated fraction of the urine and identified by gas chromatography-mass spectrometry and by proton magnetic resonance spectroscopy. The major metabolites were side-chain hydroxylated monocarboxylic acids. Three side-chain monocarboxylic acids hydroxylated in allylic positions in the isoprene moiety were also characterized. The metabolites 4″-hydroxy-Δ1-THC-7-oic acid and 7-hydroxy-4”,5″-bisnor-Δ1-THC-3”-oic acid were hitherto not identified. An earlier described dicarboxylic metabolite was present in high concentration. Further, the identity of an O-glucuronide as an in vivo urinary metabolite of Δ1-THC was here for the first time unambiguously established by m.s. and p.m.r.
An in vitro study of drug displacement interactions: warfarin-salicylate and warfarin-phenylbutazone
Authors: Aarons Leon J , Schary William L , Rowland Malcolm 
Published: April 2011

Abstract
The binding interactions between warfarin-salicylate and warfarin-phenylbutazone in the presence of 4 g percent bovine serum albumin at 37 °C were studied using equilibrium dialysis. Methods of representing and analysing drug binding interactions are discussed. Scatchard plots, double reciprocal plots and the like are shown to be of no use in representing drug displacement interactions since they display only one drug and they can be potentially misleading. It is argued that a preferable method of analysing drug displacement interaction data is in terms of a stepwise multiple equilibria model. The numerical problems associated with fitting this kind of model to the data are discussed. A three-dimensional representation of the binding surface is proposed as a superior means of visualizing drug displacement interactions.
The distribution of amylobarbitone, butobarbitone, pentobarbitone and quinalbarbitone and the hydroxylated metabolites in man
Authors: Robinson Ann E , McDowall R D 
Published: April 2011

Abstract
Fluid and tissue specimens collected from 30 subjects at autopsy have been assayed for their content of common sedative barbiturates and the corresponding hydroxylated metabolites by g.l.c. Where one barbiturate had been ingested an inverse relationship between lipid solubility of the drug and the distribution in fluids and tissues was observed. In most cases the liver, and in the remainder the spleen, contained the highest concentrations of barbiturate. Bile concentrations were often in excess of those in the corresponding liver. The metabolites of the four sedative barbiturates were usually present in lower amounts than the parent drugs in the fluids and tissues of most subjects but urine often contained much higher concentrations of metabolites—sometimes exceeding that of the parent drug in the liver. Administration of two or more barbiturates together did not appear to affect the distribution and metabolism of the individual drugs.
Effects of the non-steroidal anti-inflammatory drug benoxaprofen on leucocyte migration
Authors: Meacock S C R , Kitchen E Ann 
Published: April 2011

Abstract
Possible modes of action of the anti-inflammatory drug, benoxaprofen, have been explored. The drug caused inhibition of leucocyte migration, principally of mononuclear cells into the pleural cavity of rats undergoing carrageenan-induced pleurisy. Evidence was obtained from in vitro leucocyte migration and chemotaxis models that the drug acted directly on the mononuclear cells rather than by inhibition of chemotactic factors.
Catalytic tritiation of drugs and analysis of the tritium distribution by 3H n.m.r. spectroscopy
Authors: Elvidge J A , Jones J R , Saljoughian M 
Published: April 2011

Abstract
Propranolol, phenobartitone, diphenylhydantoin, amphetamine, imipramine and propoxyphene have been tritiated using tritiated water and platinum catalyst (from the dioxide and sodium borohydride), and the pattern of labelling has been ascertained by 3H n.m.r. spectroscopy. The results show that this exchange procedure can lead to satisfactory incorporation of tritium at ‘stable’ aromatic positions. For imipramine where incorporation of tritium was low, an alternative acid-catalysed procedure was satisfactory.
Biological effectiveness, in goldfish, of some p-substituted acetanilides alone and in the presence of poloxamers
Authors: Collett J H , Tobin Elizabeth A 
Published: April 2011

Abstract
The death times of goldfish have been measured in aqueous solutions containing different concentrations of p-substituted acetanilides alone or in the presence of poloxamers. Plots of reciprocal death time versus concentration were linear with a positive concentration intercept, the minimum effective concentration (MEC). The MEC values were directly related to the π value (hydrophobic-lipophilic constant) of the functional group on the acetanilide indicating that activity is directly related to lipophilicity. Slopes of reciprocal death time versus drug concentration were linearly related to π values but there was no direct dependence. The presence of poloxamers in aqueous acetanilide solutions reduced the goldfish death time. The effect of the poloxamers is believed to be one of rendering the goldfish membrane more permeable to drugs.
Effect of ethanol on adrenaline-stimulated glucose uptake in rat white adipose tissue
Authors: Itaya Koichi 
Published: April 2011

Abstract
The effect of ethanol on adrenaline-stimulated glucose uptake by rat white adipose tissue has been examined in vitro. Ethanol (3%) inhibited the stimulatory effect of adrenaline on glucose uptake whereas it failed to inhibit the effect of adrenaline on free fatty acid production. Addition of calcium (12·5mM) to the incubation medium restored adrenaline's effect on glucose uptake. Addition of propranolol also restored the effect of adrenaline inhibited by ethanol. Ethanol did not inhibit insulin-stimulated glucose uptake. These results suggest that ethanol modifies the coupling of the adrenoceptor to the glucose transport system in adipose tissue that is stimulated by adrenaline.
The effects of some sweetening agents and osmotic pressure on the intestinal absorption of sulfafurazole in the rat
Authors: Marvola Martti , Reinikainen Aini , Heliövaara Marja-Leena , Huikari Ansa 
Published: April 2011

Abstract
The effects of some sugars and osmotic pressure have been examined on the absorption of sulfafurazole in the rat. Statistically significant correlations were found among the hypertonic solutions between the reciprocal of osmotic pressure and AUCO-∞ or Cmax. In addition, negative correlation existed between plasma concentrations at 15 min and osmotic pressure. No significant correlations were noted among the hypotonic solutions. More attention should be paid to the osmotic pressure of formulations. The osmotic pressure of hypertonic solutions, especially, might affect absorption of drug from its dosage form.
Inter-relationships between solubilities, distribution coefficients and melting points of some substituted benzoic and phenylacetic acids
Authors: Armstrong N A , James K C , Wong C K 
Published: April 2011

Abstract
Ten 4-hydroxy and 4-alkoxy benzoic and phenylalkanoic acids have been investigated. Solubilities in aqueous buffer at pH 1·2 were determined, together with distribution coefficients between the buffer and either octanol or isopropyl myristate. When plotted against the total number of carbon atoms in the side chains, log octanol/water distribution coefficients gave two parallel straight lines, one for the substituted benzoic acids, and the other for the substituted phenylalkanoic acids. The slopes approximated to 0·5, the generally accepted value for methylene. Similar plots could be obtained with isopropyl myristate, provided the hydroxy acid results were ignored, and also when log aqueous solubilities were plotted against carbon number, although there was considerable scatter. The differences between the distribution coefficient results were explained in terms of solute-solvent interactions, and the scatter attributed to variations in the heats of fusion of the solutes. Yalkowsky's equation (1977), linking aqueous solubilities and melting points with distribution coefficients, was applied to the results, and found to be of limited predictive value.
The effects of physicochemical properties of pethidine and its basic metabolites on their buccal absorption and renal elimination
Authors: Chan Kelvin 
Published: April 2011

Abstract
The pKa values, RF values, partition coefficients between n-heptane and phosphate buffer (pH = 7·4), and buccal absorption tests of pethidine and its basic metabolites, norpethidine and pethidine N-oxide, have been determined. The amounts of these compounds recovered in the 48 h urine samples after intramuscular administration of pethidine (1·5 mg kg−1) to six healthy subjects varies with urinary pH values: the recovery from acidic urine (pH 5·0) is 15·2 to 52·0%, 6·7 to 12·9% and 0·2 to 2·3% of dose for pethidine, norpethidine and pethidine N-oxide respectively; in alkaline urine (pH 8·0) the values are 0·8 to 1·8%, 0·6 to 2·8% and 0·3 to 2·1% respectively. The physicochemical properties (pKa values, RF values, partition coefficients) and buccal absorption of pethidine, norpethidine and pethidine N-oxide are in good agreement with the pattern of their renal elimination in acidic and alkaline urine conditions. The contribution of the physicochemical properties of pethidine and its metabolites to the drug's disposition in the body and the effect of urinary pH on its metabolism should be taken into account in pharmacokinetic studies and interpretation of intersubject variation in response to pethidine.
Role of the dopaminergic system in the cataleptogenic action of bulbocapnine
Authors: Massotti M , Longo V G 
Published: April 2011

Abstract
Time courses of the behavioural and biochemical effects of a cataleptogenic dose (50mgkg−1 i.p.) of bulbocapnine have been studied in the rat. Catalepsy ensues immediately after administration of the drug and lasts 1 h. Concomitant with the onset of catalepsy there is a rise in HVA and DOPAC concentrations in whole and discrete parts of the brain (striatum, limbic system). Dopamine content does not change in whole brain but it decreases in the striatum and increases in the cortex and hippocampus. No significant effects on NA, 5-HT and 5 HIAA concentrations were observed.
Age and strain differences in the rate of development of functional tolerance to ethanol by mice
Authors: Grieve Susan J , Littleton John M 
Published: April 2011

Abstract
The time course of development of functional tolerance to ethanol was investigated in mice during the inhalation of ethanol vapour, using loss of righting reflex as the behavioural end-point. In male mice of the TO Swiss strain, weanling mice (18 days) showed no development of tolerance during continuous or repeated exposure to ethanol vapour for 6 h. Adolescent TO Swiss mice (35–40 days) showed rapid development of functional tolerance, reaching a state where 2x the original effective concentration of ethanol in blood was required to produce loss of righting reflex within 5 h. Older adult mice (150–200 days) showed some development of tolerance during continuous or repeated exposure to ethanol for 5 h but this was much less than that seen in adolescent mice. When adolescent males of the C57BL, TO Swiss and DBA2 strains were compared, marked differences were observed. C57BL mice showed very rapid development of functional tolerance to ethanol in which more than 2 × the original effective dose was required to produce loss of righting reflex after about 3 h of ethanol exposure. TO Swiss mice showed somewhat slower development of ethanol tolerance. DBA2 mice showed little evidence of development of functional tolerance over the time course of these experiments. Evidence was also obtained that similar age and strain differences may exist with respect to tolerance to the hypothermic effects of ethanol. These results are discussed in relation to current concepts of ethanol sensitivity, tolerance and physical dependence.
Serum and peritoneal fluid concentrations of clindamycin and lincomycin in the mouse
Authors: Rosen A , Kanwar R S , Dempsey G , Brookes L G 
Published: April 2011

Abstract
Serum concentrations of drug were obtained at various times after intramuscular dosing of healthy mice with either clindamycin or lincomycin hydrochlorides. Washings from the peritoneal cavity were taken at the same time as the serum samples. Changes in drug concentration in the peritoneal fluid with time mimic those for the serum, but concentrations in peritoneal fluid are much greater than the corresponding serum concentrations. The total volume of peritoneal fluid was estimated to be 0·05 ml.
Selective influences of age and thyroid hormones on Type A monoamine oxidase of the rat heart
Authors: Lyles G A , Callingham B A 
Published: April 2011

Abstract
The specific activity of rat heart MAO, towards both tyramine and benzylamine as substrates, was found to increase with the age of the animal, and also after administration of (−)-thyroxine to young male rats. Conversely, enzyme activity was decreased in animals made hypothyroid by including 2-thiouracil in their diet. However, with both age and altered thyroid status, relatively greater changes in the deamination of tyramine rather than in that of benzylamine, were obtained. Clorgyline and deprenyl, used as inhibitors of rat heart MAO, indicated that tyramine is metabolized solely by MAO-A, whereas benzylamine is a substrate for both MAO-A and -B, and also a clorgyline- and deprenyl-resistant enzymic activity. The proportional contribution of MAO-A, -B and the clorgyline-resistant enzyme towards the total benzylamine deamination in the rat heart was found to vary with the age and with altered thyroid status of the animal in such a way that selective changes in the activity of MAO-A appear to be largely responsible for the overall changes in the specific activity of rat heart MAO which occur in response to these developmental factors.
Inhibitory effect of 5-hydroxytryptamine on lipogenesis in rat adipose tissues
Authors: Itaya Koichi 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) inhibited the incorporation of 14C from 14C-labelIed glucose, pyruvate, citrate and acetate into fatty acids but it did not inhibit the conversion of 14C from citrate and acetate into CO2, and the citrate conversion into glyceride-glycerol in epididymal and mesenteric adipose tissue from 24h-fasted rats. 5-HT stimulated the formation of lactate from glucose and pyruvate, and increased the ratio of lactate produced/pyruvate taken up. This ratio was similar to the NADH:NAD ratio. These results indicate that 5-HT inhibits fatty acid synthesis in rat white adipose tissue by mechanisms similar to those of the catecholamines.
The effect of low- and high-humidity ageing on the hardness, disintegration time and dissolution rate of dibasic calcium phosphate-based tablets
Authors: Chowhan Z T 
Published: April 2011

Abstract
The effect of low- and high-humidity ageing on hardness, disintegration time and dissolution rate of dibasic calcium phosphate dihydrate-based tablets prepared at different initial moisture concentrations was studied. Hardness increased while disintegration and dissolution rate decreased on ageing in low humidity. The dissolution rate of tablets containing higher initial moisture was slower than the tablets containing lower initial moisture. On ageing in high humidity, hardness, disintegration and dissolution rates decreased at all initial moistures. The results suggest that the effects of moisture and humidity should be thoroughly investigated for dibasic calcium phosphate dihydrate-based tablets in order to ensure stability and bioavailability of the drug.
Sympathomimetic effects of exo- and endo- isomers of 2-aminobenzonorbornene in vitro and in vivo
Authors: Burn P , Crooks P A , Ratcliffe B L , Rees J M H 
Published: April 2011

Abstract
A stereospecific synthesis of endo-2-aminobenzornorbornene is described. Its sympathomimetic activities and those of its N-methyl derivative were compared with the equivalent exo- isomers using the isolated rat anococcygeus muscle and the anaesthetized rat blood pressure preparations. On the anococcygeus muscle preparation the endo- and exo-isomers of the primary amines had similar indirectly acting sympathomimetic activities. In contrast the exo-N-methyl derivative was a far more potent sympathometic in vitro than the endo-N methyl isomer. In the anaesthetized rat the exo- and endo-isomers of 2-aminobenzonorbornene and their N-methyl derivatives all had similar pressor activities, though the successive injections of the two exo-derivatives suggested an additional α-adrenoceptor blocking activity. The actions of these rigid sympathomimetics are compared with those of the flexible amphetamine structure.
Facilitatory effect of nicotine on adrenergic neuroeffector transmission in the isolated ear artery of the rabbit
Authors: Sarantos-Laska Catherine , McCulloch Marian W , Rand Michael J 
Published: April 2011

Abstract
The effects of nicotine were studied on perfusion pressure and vasoconstrictor responses to sympathetic nerve stimulation in the isolated ear artery of the rabbit. Infusions of nicotine (50 μM) produced a transient increase in perfusion pressure and potentiated responses to nerve stimulation; these effects of nicotine were unaffected by atropine (0–3 μM) and abolished or significantly reduced respectively by hexamethonium (300 μM) or mecamylamine (1 μM). In experiments with ear arteries previously labelled with [3 H] noradrenaline an infusion of nicotine (50 μM) produced a transient increase in tritium efflux and the potentiation of responses to nerve stimulation in the presence of nicotine was accompanied by a statistically significant increase in stimulation-induced tritium efflux; these effects of nicotine were abolished by hexamethonium (300 μM) or mecamylamine (1 μM).
Mechanism of mesaconitine-induced contractile response in guinea-pig ileum
Authors: Sato Hiroshi , Ito Tomoko , Ohizumi Yasushi , Hikino Hiroshi 
Published: April 2011

Abstract
Mesaconitine (MA) caused contractions of the guinea-pig isolated ileum in a dose-dependent manner (10−8 −10−5 g ml−1), slightly potentiated the contractile response to acetylcholine (ACh) and histamine and enhanced responses to electrical stimulation. Repeated application of MA (10−5 g ml−1) produced tachyphylaxis. Atropine blocked contractions to MA (3 times 10−7 g ml−1), but only partially those to MA (10−5 g ml−1). Morphine, strychnine and hemicholinium-3, but not hexamethonium, also inhibited MA-induced contractions. Contractions produced by both doses of MA were abolished by cocaine, tetrodotoxin, or noradrenaline, or by previous cooling of the ileum. The atropine-resistant contractions produced by MA (10−5 g ml−1) were blocked by indomethacin. MA (3 times 10−7 −10−5 g ml−1) elicited a dose-dependent release of ACh from the isolated ileum which was blocked by treatment with tetrodotoxin or cocaine, or exclusion of calcium ions from the bath. It is concluded that the contractions induced by lower doses of MA are brought about by the release of ACh from the postganglionic cholinergic nerve and that the contractions by higher doses could also be mediated by release of prostaglandins from the ileum.
The influence of molecular size and pH on the macrocationic inhibition of pepsin by polylysine
Authors: Anderson W , Harthill J E , Rahmatalla R 
Published: April 2011

Abstract
Polylysines of 7–371 lysine residues inhibited pepsin over the pH range 3·6-5·0 in a system using azocoll as substrate. Tetralysine was inactive. An almost 1: 1 molar ratio with pepsin gave maximum inhibition for a polylysine containing 59 lysine residues but increase in polylysine molecular size beyond this size was not accompanied by increase in activity on a weight basis although the polylysine: pepsin molar ratio for maximum inhibition decreased and inhibition mechanism varied. Polylysines of 59 and 158 lysine residues which were intermediate in the series were non-competitive inhibitors, whilst polylysines of greater and smaller molecular size were competitive inhibitors, although only the smallest inhibitory polylysine, containing 7 lysine residues, was a pure competitive inhibitor. Polylysine inhibition of pepsin was found to be strongest at pH 5·0 and the pH dependence appeared to be associated with the relative concentrations of the enzyme and inhibitors in ionized form. For each polylysine it was possible to detect a polylysine: pepsin concentration ratio for which inhibition was pH-independent over the range 3·6-5·0.