bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of seizures elicited by the benzodiazepine Ro 5–3663—a comparison with picrotoxin
Authors: File Sandra E 
Published: April 2011

Abstract
Ro 5–3663 is a convulsant 1,4-benzodiazepine that does not act at the benzodiazepine, but at the picrotoxin, site. To characterize the behavioural actions of Ro 5–3663, a comparison was made between its effects and those of picrotoxin, when combined with several compounds that act at the GABA-benzodiazepine receptor complex. The quinolines, PK 8165, PK 9084 and CGS 8216 caused myoclonic jerks when combined with subconvulsant doses of Ro 5–3663 or picrotoxin; in combination with picrotoxin they also caused full tonic-clonic convulsions. Ro 15–1788 (1, 10mg kg−1) caused myoclonic jerks when it was given 10 min before, or at the same time as, subconvulsant doses of either compound. Diazepam (2, 4 mg kg1) was anticonvulsant against both compounds. However, Ro 15–1788 (10,20 mg kg−1, 20 min before), PK 8165 (80 mg kg−1) and PK 9084 (60mgkg−1) were effective only against the convulsions induced by Ro 5–3663. It is not possible to determine whether these differences between Ro 5–3663 and picrotoxin are quantitative or qualitative.
Adenosine mechanisms are not affected by antidepressant concentrations of desipramine
Authors: Jonzon Bror , Fredholm Bertil B 
Published: April 2011

Abstract
We have evaluated the proposal that adenosine may mediate some of the effects of tricyclic antidepressant therapy. In-vitro desipramine (DMI) (1–10 μm) did not affect adenosine or 2-chloroadenosine-induced inhibition of lipolysis or the adenosine stimulated formation of cyclic (c)AMP in the hippocampal slice. However, very high concentrations of desipramine (0·2–0·5 mm) as well as some detergents potentiated the stimulatory effect of adenosine on cAMP formation. The ATP, ADP and AMP contents in slices were unaffected as was the electrically evoked release of purines. Long-term treatment in-vivo with antidepressants in clinically relevant doses did not alter the sensitivity of adenosine receptor mediated cAMP formation in-vitro while the β-adrenoceptor-mediated formation was depressed by desipramine or imipramine treatment but not by zimelidine or fluoxetine treatment. It is concluded that actions on central adenosine mechanisms are unlikely to play any important role in the therapeutic effects of tricyclic antidepressants.
The development of a relative hyperthermia during continuous clonidine infusion in the rat
Authors: Maccarrone C , Lewis S J , Jarrott B 
Published: April 2011

Abstract
In rats the continuous infusion of clonidine (10 μg kg−1 h−1) produces a relative hyperthermia of approximately 0·6 °C during the light phases but not the dark phases of a 10 day infusion period. It appears that the relative hyperthermia results from a clonidine infusion-induced attenuation of the fall in body temperature which normally occurs at the onset of the light phases.
The opacity of tablet film coatings
Authors: Rowe R C 
Published: April 2011

Abstract
The opacity of tablet film coatings containing a variety of pigments and fillers has been assessed using a contrast ratio defined as the ratio of the measured reflectance of the incident light when the film is placed on a black substrate to the measured reflectance of the incident light when the film is placed on a white substrate. Films pigmented with calcium carbonate, calcium sulphate or talc had very low contrast ratios and only the inclusion of titanium dioxide imparted opacity. Films pigmented with the coloured lake pigments had contrast ratios dependent on both the parent dye and the dye concentration with the contrast ratios decreasing blue &gt; red &gt; orange &gt; yellow. Films pigmented with the synthetic iron oxides all had very high contrast ratios. The results are consistent with the known theories of light scattering and absorption and illustrate the potential of this accurate, rapid and simple technique in the optimization of film formulations during product development.
Passive inhalation of cannabis smoke
Authors: Law B , Mason P A , Moffat A C , King L J , Marks V 
Published: April 2011

Abstract
Six volunteers each smoked simultaneously, in a small unventilated room (volume 27 950 litre), a cannabis cigarette containing 17·1 mg Δ9-tetrahydrocannabinol (THC). A further four subjects – passive inhalers – remained in the room during smoking and afterwards for a total of 3 h. Blood and urine samples were taken from all ten subjects and analysed by radioimmunoassay for THC metabolites. The blood samples from the passive subjects taken up to 3 h after the start of exposure to cannabis smoke showed a complete absence of cannabinoids. In contrast, their urine samples taken up to 6 h after exposure showed significant concentrations of cannabinoid metabolites (≤6·8 ng ml−1). These data, taken with the results of other workers, show passive inhalation of cannabis smoke to be possible. These results have important implications for forensic toxicologists who are frequently called upon to interpret cannabinoid levels in body fluids.
Sulfinpyrazone increases the number of β-adrenoceptors on intact human lymphocytes
Authors: De Blasi Antonio , Costantini Carlo 
Published: April 2011

Abstract
Sulfinpyrazone increased the number of β-adrenoceptors (+17–40%) on intact human lymphocytes at concentrations ranging from 10−5 to 2 times 10−4 m. It affected the Bmax (187 ± 6 and 142 ± 5 fmol mg−1 protein respectively with and without sulfinpyrazone, P &lt; 0·001) but did not influence KD (4·4 ± 0·3 and 4·6 ± 0·7 nm with and without the drug). This effect was observed on either washed or unwashed lymphocyte membrane preparations. These findings have several pharmacological and therapeutic implications.
Kinetics and distribution of the β-adrenergic agonist salbutamol in rat brain
Authors: Caccia S , Fong M H 
Published: April 2011

Abstract
The kinetics of the β-adrenergic agonist salbutamol and its distribution in the central nervous system were examined in rats by high-performance liquid chromatography with electrochemical detection. After 10 mg kg−1 i.v. salbutamol, the decline in drug plasma concentrations was biphasic and salbutamol was cleare every rapidly with a β-half-life of about 37 min. Salbutamol rapidly penetrated the ‘blood-brain barrier’ and reached brain concentrations amounting to about 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands) the drug achieved concentrations more than 100 times those in whole brain. The results support the hypothesis that stimulation of central β-adrenergic sites is responsible for salbutamol’s pharmacological and biochemical effects.
The putative 5-HT1 receptor agonist, RU 24969, inhibits the efflux of 5-hydroxytryptamine from rat frontal cortex slices by stimulation of the 5-HT autoreceptor
Authors: Middlemiss Derek N 
Published: April 2011

Abstract
The putative central 5-HT receptor agonist, 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole succinate (RU 24969), was found to be a potent inhibitor of the continuous K+ evoked efflux of [3H]5-HT from superfused rat frontal cortex slices (pD2 7.45). The effects of RU 24969 were attenuated by the putative 5-HT autoreceptor antagonists, methiothepin, quipazine and (-)-propranolol but not by the α2-adrenoceptor antagonist, idazoxan. It is concluded that RU 24969 inhibits K+ evoked efflux of [3H]5-HT from rat frontal cortex slices by stimulation of the 5-HT autoreceptor. Moreover, since RU 24969 potently displaced ligand binding to the 5-HT1 and 5-HT1B recognition sites but was only weakly active at the 5-HT2 receptor, the results lend support to the claim for a pharmacological resemblance between the 5-HT autoreceptor and the 5-HT1 recognition site and in particular the low affinity 5-HT1B subtype.
Comparative potencies of calcium channel antagonists and antischizophrenic drugs on central and peripheral calcium channel binding sites
Authors: Quirion Rémi , Lafaille F , Nair N P V 
Published: April 2011

Abstract
Dihydropyridines are potent agents on [3H]nitrendipine binding sites in heart and brain membranes. Like the phenylalkylamines, they are slightly more active on heart than on brain [3H]nitrendipine binding sites. On the other hand, the diphenylalkylamines, the diphenylpiperazines and the antischizophrenic drugs of the diphenylbutylpiperidine type are more potent on brain [3H]nitrendipine binding sites. The findings suggest tissue heterogeneity of [3H]nitrendipine binding sites and the possible development of diphenylbutylpiperidine-diphenylbutylpiperazine analogues that could selectively act on brain calcium channel antagonist binding sites.
Influence of serum protein binding on hepatic clearance of S-disopyramide in the rabbit
Authors: Huang Jin-Ding , Øie Svein 
Published: April 2011

Abstract
The effect of changing the protein binding of S-disopyramide, a compound that is highly extracted by the liver on its hepatic clearance in rabbits is described. Using indocyanine green clearance as a means of measuring hepatic blood flow, qualitative changes were observed which are in agreement with the results predicted by both the ‘parallel tube’ and the ‘well-stirred’ models. However, neither model alone could explain the quantitative changes. Suggestions are put forward to explain these results.
Possible mechanisms of inhibitory action of protamine on contractile activity of rat aorta
Authors: Uruno Tsutomu , Matsumoto Ryuji , Okushita Keiko , Sunagane Nobuyoshi , Kubota Kazuhiko 
Published: April 2011

Abstract
Experiments were performed to determine possible mechanisms of inhibitory action of protamine chloride on noradrenaline (10 μM)-, KCl (40 mM)-, BaCl2 (1 mM)- and CaCl2 (10 mM)-induced contractions in rat aorta. Protamine, La3+ and gallopamil (D600), inhibited the K+-induced contractions more effectively than the noradrenaline-induced responses on the basis of the concentrations giving 40% inhibition. Lanthanum (1–5 mM) reduced tissue Ca content in both normal and Ca2+-depleted Tris-buffered solutions and produced an increase in 45Ca efflux from the aortic strip into the Ca2+-depleted Tris solution. Protamine (1–5 mg ml−1) reduced tissue Ca content in normal Tris solution, but to a lesser extent than La3+ in the Ca2+-depleted solution. Furthermore, protamine (2 mg ml−1) produced no increase in 45Ca efflux from aorta. These results suggest that protamine chloride may preferentially inhibit the Ca2+ influx stimulated by K+ depolarization and that its inhibitory action on rat aorta may be due to non-specific displacement of the superficially located bound Ca2+ of the cell membrane, which can also be readily removed by treatment with Ca2+-depleted solution.
Cardiorespiratory depression and haemolysis due to thioridazine overdose in the rat
Authors: Langemeijer J J M , De Wildt D J , De Groot G , Sangster B 
Published: April 2011

Abstract
The cardiovascular and respiratory effects of an intravenous overdose of thioridazine (125 mg kg−1 h−1) were examined in either spontaneously breathing or artificially ventilated urethane-anaesthetized rats. In both groups Po2, heart rate and mean arterial pressure decreased and atrioventricular and intraventricular conduction time, as well as QT time, increased similarly. Pco2 and pH did not differ significantly except in spontaneously breathing rats where a severe acidosis occurred at the end of the experiments. Haemolysis was suspected. The same dose was administered intravenously to artificially ventilated rats. Plasma concentrations of the drug and its main metabolites, haematocrit and free plasma Hb were determined in separate groups. A severe haemolysis was observed. Thioridazine administered in the same doses intragastrically, intraduodenally or intraperitoneally resulted in lower plasma values than after intravenous administration and there was no haemolysis. Much higher oral doses produced haemolysis at 36 h, at which time plasma concentrations were not higher than those recorded after administration via the other non-intravenous routes. It is probable that the observed changes in cardiovascular and respiratory parameters are partly the result of haemolysis following thioridazine administration.
Effect of 6-hydroxydopamine on the metabolism of endogenous octopamines and catecholamines
Authors: Ibrahim Kamal E , Williams Clyde M 
Published: April 2011

Abstract
The daily excretion in rat urine of o-(OHMA) (0.2), m-(MHMA) (0.9), p-(PHMA) hydroxymandelic acid (78), vanillylmandelic acid (VMA) (3.5) and homovanillic acid (30 μg day−1), terminal metabolites of the isomeric octopamines and catecholamines, has been determined by gas chromatography-mass spectrometry. Chemical sympathectomy with 6-hydroxydopamine (i.p.) caused the daily output of each acid (except OHMA) to drop by 50% and that of PHMA was restored to normal the most rapidly after cessation of treatment. These results indicate that m-and p-(but not o-) octopamine coexist with catecholamines in sympathetic nerve terminals, are subject to the same compensatory biosynthetic mechanism following chemical sympathectomy and that p-octopamine has the highest turnover rate of these biogenic amines in the rat.
The nasal absorption of sodium cromoglycate in the albino rat
Authors: Fisher A N , Brown K , Davis S S , PARR G D , Smith D A 
Published: April 2011

Abstract
The intranasal absorption of sodium cromoglycate has been investigated in the adult male COBS/Wistar rat. Sodium cromoglycate (1 mg kg−1) was instilled into the nasal cavities and for comparison animals were also similarly dosed intravenously or sublingually. Serial samples of blood or bile were collected. After intravenous administration, the area under the plasma concentration curve (AUC0-∞) was 32 μg min ml−1 corresponding to a plasma clearance of 13 ml min−1 and an elimination rate constant of 0.049 min−1. Plasma concentrations of radioactivity after intranasal administration rose to a mean peak of 0.3 μg ml−1 approximately 20 min after dosing and fell to 0.03 μg ml−1 at 3 h. The AUC0-3 was 19 μg min ml−1 corresponding to an absorption of 60% over 3 h. The absorption rate constant (ka) was 0.059 min−1. The total amount of sodium cromoglycate excreted in bile after intravenous administration was 56%. The amount of compound excreted in the bile was 30% after intranasal administration corresponding to an absorption of 53%. Plasma and bile data therefore show good agreement. Total excretion in the bile over 3h after sub-lingual administration was 3%, demonstrating that this route made no significant contribution to the intranasal results. The absorption of sodium cromoglycate is independent of variations in the technique including changes in the orientation of the rat or blocking of the nasopalatine. The techniques used minimized other competing nasal clearance processes such as mucociliary clearance.
Inhibition of mouse epidermal 12-lipoxygenase by 2,3,4-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-l,4-benzoquinone (AA861)
Authors: Nakadate Teruo , Yamamoto Satoshi , Aizu Eriko , Kato Ryuichi 
Published: April 2011

Abstract
2,3,5-Trimethyl-6-(12-hydroxy-5, 10-dodecadiynyl)-1.4-benzoquinone (AA861) strongly inhibited epidermal lipoxygenase activity which was determined by the formation of [14 C]12-hydroxy-5,8,10,14-eicosatetraenoic acid by incubating [l4 C]arachidonic acid with cytosol fraction of epidermal homogenate of ***CD-1 mice. AA861 failed to inhibit epidermal cyclooxygenase activity. The present results indicate that AA861 is a potent inhibitor of 12-lipoxygenase in mouse epidermis (IC50 1.9 μM).
Effect of dopaminergic drugs on striatal acetylcholine concentration
Authors: Sethy Vimala H , Wenger Dora 
Published: April 2011

Abstract
Striatal acetylcholine concentration was determined after administration of varying doses of apomorphine, (+)-PPP and (-)-PPP to rats. (+)-PPP at 3 and 10 mg kg−1 is a dopamine agonist, whereas (-)-PPP at 0.3 and 3 mg kg−1 is a dopamine antagonist in the striatum.
Effects of interacting variables on the tensile strengths and disintegration times of paracetamol tablets
Authors: Bangudu A B , Pilpel N 
Published: April 2011

Abstract
The effects of separately varying the packing fraction (P), the proportions of microcrystalline cellulose, Avicel (A) and alginic acid, disintegrant (D), on both the tensile strengths and disintegration times of paracetamol tablets are in the order P » A » D. The combined effects of these variables on both tensile strength and disintegration time are A x P » D x P &gt; A x D.
Indirect dopaminergic effects of tofisopam, a 2,3-benzodiazepine, and their inhibition by lithium
Authors: Chopin Philippe , Stenger Antoine , Couzinier Jean-Pierre , Briley Mike 
Published: April 2011

Abstract
Tofisopam, a 2,3-benzodiazepine, has been shown to have anxiolytic activity. However, in contrast to the widely used 1,4-benzodiazepines, it has no anticonvulsant, sedative or muscle relaxant effects. Tofisopam enhanced the behavioural actions of various dopaminergic drugs, both direct agonists, such as apomorphine (climbing behaviour in mice), and indirect agonists, such as (+)-amphetamine and amineptine (jumping behaviour in mice). Chronic treatment with lithium abolished the tofisopam-induced increase in the activity of these dopaminergic drugs. Thus tofisopam appears to induce acutely an increase in the sensitivity of central dopaminergic receptors which can be prevented by pretreatment with lithium.
Phenobarbitone enhances [35S]TBPS binding to extensively washed rat cortical membranes
Authors: Honoré Tage , Drejer Jørgen 
Published: April 2011

Abstract
Pentobarbitone and phenobarbitone enhance [35S]TBPS binding to extensively washed rat cortical membranes with ED50 values of 15 and 120 μM, respectively, indicative of an interaction with the chloride ionophore part of the GABA-receptor different from the TBPS binding site, but allos-terically coupled to this site.
Polymorphism in metoclopramide hydrochloride and metoclopramide
Authors: Mitchell A G 
Published: April 2011

Abstract
Metoclopramide hydrochloride (MCPHCl.H2O) and metoclopramide base (MCP) have been studied by DSC, thermomicroscopy, X-ray diffraction and infrared spectroscopy. MCPHCl.H2O does not readily lose water of crystallization either from the solid state or from the melt, but depending on the conditions, dehydration can give rise to two anhydrous polymorphs, MCPHCl/Form I (mp 187 °C) and MCPHCL/Form II (mp 155 °C). Form I crystallizes from the melt of Form II and not by a reversible solid-solid transition. The anhydrous hydrochloride therefore shows monotropic polymorphism where Form I is the stable polymorph and Form II, a metastable polymorph. Thermal analysis of MCP shows that the base exists as two enantiotropic polymorphs. The transition of the form stable at room temperature (MCP/Form I) to the form stable at high temperatures (MCP/Form II mp 147 °C) occurs extremely rapidly at 125 °C but the reverse process requires one month at room temperature ($22 °C). It is therefore possible to compare the X-ray diffraction powder patterns and infrared spectra of MCP Forms I and II.
Properties of amiodarone monolayer spread at the air–water interface
Authors: Ferreira Jeanine , Brasseur Robert , Chatelain Pierre , Ruysschaert Jean-Marie 
Published: April 2011

Abstract
Surface pressure measurements demonstrate that, over a wide range of pH, amiodarone forms a stable monolayer at the air–water interface. The area found to be occupied by an amiodarone molecule was compared with a theoretical prediction based on a conformational analysis, making it possible to assemble amphiphilic molecules. The intrinsic ionization constant of amiodarone in an aqueous environment pKi = 8.7 ± 0.5 was evaluated from surface potential measurements.
Plasma concentrations and pharmacokinetics of midazolam during anaesthesia
Authors: Crevat-Pisano P , Dragna S , Granthil C , Coassolo P , Cano J P , Francois G 
Published: April 2011

Abstract
Midazolam and 1-hydroxymidazolam plasma concentrations have been monitored and pharmacokinetic parameters of midazolam estimated during anaesthesia induced and Maintained by its repeated injection according to two protocols (3 × 0.3 mg kg−1 at 45 min intervals or an induction dose of 0.3 mg kg−1 with maintenance doses of 0.15 mg kg−1 at 30 min intervals). Minimum plasma concentrations of midazolam measured just before each injection were 258.8 ± 108.4 ng ml−1 for the first protocol and 353.1 ± 55.2 ng ml−1 for the second protocol; maximum midazolam concentrations, measured 5 min after the last administration, were 1103.1 ± 237.9 ng ml−1 and 743.0 ± 103.2 ng ml−1, respectively, suggesting that a continuous infusion of midazolam after a loading dose should be better than repeated injections at keeping the concentration close to the sedative level of 400 ng ml−1. The estimated pharmacokinetic parameters were similar to those already published, except for the β elimination half-life of midazolam (3.24 ± 0.90 h for protocol 1 and 3.34 ± 1.47 h for protocol 2) which was slightly longer than that reported for single dose studies. The comparison of plasma determinations, obtained either by gas-liquid chromatography or by a radioreceptor assay technicjue, clearly showed that 1-hydroxymidazolam, even after repeated midazolam administration, was not present at a concentration sufficient to affect the overall pharmacological activity of the parent drug.
Pharmacological characterization of the postsynaptic α-adrenoceptors in human uterine artery
Authors: Ribeiro C A Fontes , Macedo Tice A 
Published: April 2011

Abstract
Prazosin and yohimbine were used to differentiate postjunctional α-adrenoceptors in the human uterine artery in-vitro. Two postjunctional α-adrenoceptor subtypes were distinguished by the affinities of the receptor for yohimbine and prazosin. The pA2 for prazosin was 8.91 against phenylephrine with a slope not significantly different from unity (0.91), and the pA2 for yohimbine was 7.25 against naphazoline and 8.70 against clonidine, with slopes not significantly different from unity (1.11 and 1.18, respectively). Yohimbine was not very active against phenylephrine, while prazosin was very active against the mixed and selective α2-adrenoceptor agonist noradrenaline and clonidine; the intercepts of the Schild plot were 8.80 and 8.82 but with slopes significantly less than unity (0.77 and 0.67, respectively). Prazosin competitively antagonized phenylephrine at the α1-adrenoceptor, whereas yohimbine competitively antagonized naphazoline and clonidine at the α2-adrenoceptor. It is concluded that both α1- and α2-adrenoceptors are present in the human uterine artery.
Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine
Authors: Segura Jordi , Garcia Inocencio , Tarrus Emili 
Published: April 2011

Abstract
After administration of furafylline, a, 1,3,8-trisubstituted xanthine, to beagle dogs at 0.5 and 10 mg kg−1 an elimination half-life 2–10 times longer than that of theophylline was observed. The kinetics were dose-dependent but no phase I metabolites were detected. When the compound was given orally to humans at a dose of 1.3–1.9 mg kg−1 a mean β elimination half-life of 48.1 ± 10.8 h was obtained after an initial distribution phase. Evidence of non-linear kinetics for plasma levels below 0.6 μg ml−1 was also obtained. Other 1,3,8-trisubstituted xanthines, may also have a lower elimination rate than theophylline.