bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Metoclopramide on the Absorption and Pharmacology of Chlorpromazine in the Rat
Authors: Imamura Y , Harada S , Okano Y , Miyata T , Otagiri M 
Published: April 2011

Abstract
The mechanism of interaction between metoclopramide (MCP) and chlorpromazine (CPZ) has been examined in rats. MCP given intraperitoneally 30 min before orally administered CPZ significantly enhanced the cataleptic and hypothermic effects of CPZ, and also initially increased its plasma and brain concentrations. However, MCP had no effect on the plasma and brain concentrations of CPZ given as an intravenous bolus, indicating that MCP interacts with CPZ during its intestinal absorption. Furthermore, co-administration of MCP (i.p.) with CPZ (p.o.) markedly accelerated gastric emptying compared with CPZ alone, and MCP (i.v.) did not alter the uptake of CPZ by the intestinal membrane. Therefore, it is concluded that MCP causes an increase in the rate of CPZ absorption, by accelerating the gastric emptying.
Different Ability of Trifluoperazine to Inhibit Agonist-induced Contraction of Lung Parenchyma Strips from Control and Sensitized Guinea-pigs
Authors: Sanz Celia , Cortijo Julio , Perpin̄á Miguel , Esplugues Juan , Morcillo Esteban J 
Published: April 2011

Abstract
There is increasing interest in the therapeutic potential of calcium antagonists in asthma. Among them the use of calmodulin antagonists deserves consideration. In the present work the effect of trifluoperazine on contractions generated by different mechanisms (CaCl2, KCl, acetylcholine, histamine and 5-hydroxytryptamine) in lung parenchyma strip isolated from control and actively sensitized guinea-pigs has been studied. Trifluoperazine produced both in unsensitized and sensitized lung strips, a concentration-dependent, right, downward displacement of the concentration-response curves to the agonists used, although the sensitization procedure resulted in a potentiation in the ability of trifluoperazine to inhibit agonist-induced contractions. The basis for this greater potency of trifluoperazine in sensitized tissues remains to be elucidated but raises attention to the future use of selective calmodulin antagonists in the management of asthma.
The permeability of grafted human transplant skin in athymic mice
Authors: Scott Robert C , Rhodes Christopher 
Published: April 2011

Abstract
Human skin has been transplanted onto athymic mice and its permeability properties assessed to see if this in-vivo model would be of benefit in predicting accurately absorption of drugs or toxic chemicals through human skin. The permeability properties of the skin alone, and grafted and athymic mouse skin were assessed by measuring in-vitro absorption of tritiated water and a permanently charged cationic penetrant, paraquat. The grafted skin and athymic mouse skin had similar permeability to the tritiated water. However, the grafted skin was less permeable to paraquat but was more permeable to it than normal human skin, indicating that although histologically, the transplanted skin appeared normal, its barrier properties were impaired. The model was not, therefore, useful for assessing human percutaneous absorption.
Transport Characteristics of Propantheline Across Rat Intestinal Brush Border Membrane
Authors: Saitoh Hiroshi , Kawai Shinji , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
The transport mechanism of propantheline, an anti-acetylcholine quaternary ammonium compound, has been studied using brush border membrane vesicles isolated from rat small intestine. The uptake of propantheline was facilitated by the transmembrane electrical potential difference (cell interior negative) induced by NaSCN, NaI or valinomycin. But this effect was a secondary action; in the initial phase of propantheline uptake (&lt; 5 min), there was no facilitating effect. When the transmembrane potential difference was induced after propantheline uptake had reached a steady state, there was an overshoot of the drug. Therefore, it is suggested that the transport of propantheline across the brush border membrane consists of at least two processes. In the first, propantheline rapidly binds to the brush border membrane, in the second it enters into epithelium driven by the negative transmembrane electrical potential difference. Cationic tertiary amines such as chlorpromazine, imipramine and promethazine markedly inhibited propantheline uptake. These results suggest that there is a common absorption process for tertiary amines and quaternary ammonium compounds.
Depolarizing Effect of Various Local Anaesthetics on the Helix aspersa Neurons: Dose-response Relationship
Authors: Cardi P , Lartigue M , Meunier J M 
Published: April 2011

Abstract
The depolarizing effect of various local anaesthetics (LA) on the membrane potential of Helix central neurons has been examined. There is a relation between depolarizing effect and concentration of LA in the bath that is linear over a range of concentrations. The slope of the curve is significantly higher for amethocaine (tetracaine) than for procaine while for dibucaine the dose-response relation is not linear. The blockade of a response to acetylcholine (ACh) is about two fold higher for dibucaine and amethocaine than for procaine. These results suggest that both amethocaine and procaine act at the ACh-site in addition to their binding with specific sites located within the ionic channel lumen; dibucaine appears to act through another mechanism.
The Anxiolytic and Anxiogenic Actions of Ethanol in a Mouse Model
Authors: Costall B , Kelly M E , Naylor R J 
Published: April 2011

Abstract
The administration to mice of ethanol in the drinking water for 7 days modified exploratory activity (rearings/line crossings) in an anxiety testing box separated into white and black sections with an interconnecting door. During ethanol intake mice exhibited reduced anxiety responding, shown as increased rearings and line crossings in the white section, to which the mice are normally averse, with corresponding decreased behaviour in the black section. When naive mice were presented with a choice between normal drinking water and drinking water containing ethanol, they consumed sufficient of the latter to secure a full anxiolytic response, making up the total volume of fluid required by also drinking the former. A 48 h withdrawal from a 14 day treatment with ethanol caused a reversed profile of exploratory behaviour, directed preferentially at the black section of the test box, and indicative of an anxiogenic response. Diazepam, tiapride or clonidine given twice daily during withdrawal from ethanol could each secure a reduction in the withdrawal anxiogenesis. It is concluded that the simple model of anxiety described in the mouse may be useful for eludicating the mechanisms involved in the anxiolytic and anxiogenic potential of ethanol and may aid the search for novel agents having potential to suppress withdrawal anxiogenesis.
Interfacial tensions and partition coefficients in water/heptane systems containing 2,6-diisopropylphenol, n-alkylphenols and cycloalkanols
Authors: Runyan A , Perrin J H , Vilallonga F A 
Published: April 2011

Abstract
The free energies of absorption, dehydration, and transfer in a heptane-water system for a set of phenolic compounds and a series of cycloalkanols have been investigated. The free energy of adsorption depends only upon the molecular surface area of the hydrophobic fraction of the molecule, whereas the free energy of dehydration is independent of this fraction.
Modulation of cyclic AMP and autoregulation of renal blood flow, analysed by the use of forskolin and 1-methyl-3-isobutylxanthine
Authors: Ogawa Nobuyuki , Ono Hiroshl 
Published: April 2011

Abstract
We have examined the effects of forskolin and 1-methyl-3-isobutylxanthine (IBMX) in relation to cyclic (c)AMP metabolism and renal blood flow autoregulation in anaesthetized dogs. Control observations usually showed excellent autoregulation of renal blood flow over the renal perfusion pressure range of 120–200 mmHg, when the perfusion pressure was changed, stepwise, between 60 and 200 mmHg. Renal blood flow was increased by the infusion of forskolin (10 μg min−1) and IBMX (100 μg min−1) at the basal perfusion pressure of 100 mmHg, and maintained an increased level while the infusion was continued. Forskolin and IBMX did not inhibit autoregulation, though they shifted the perfusion pressure range evoking autoregulation. These data indicate that vasodilators which may produce the activity through modulating the cAMP level in vascular smooth muscle do not influence the establishment of autoregulation of renal blood flow.
In-vivo studies with the opioid antagonist, 16-methylcyprenorphine
Authors: Birch Phillip J , Hayes Ann G , Sheehan Michael J , Tyers Michael B 
Published: April 2011

Abstract
The effect of the opioid antagonist, 16-methylcyprenorphine (RX8008M), on the antinociceptive action of the μ-selective agonist, morphine, and the κ-selective agonist, U50488H, has been investigated in the mouse abdominal constriction test. RX8008M produced a dose-dependent antagonism of the antinociceptive effect of morphine, but did not antagonize the response to U50488H. RX8008M should prove a useful probe for the in-vivo characterization of the receptor selectivity of opioid drugs.
A modified transmembrane migration method for evaluating the spermicidal potency of some nonoxynol compounds
Authors: Gadd A L , Curtis-Prior P B 
Published: April 2011

Abstract
The transmembrane migration technique, a simple method in-vitro for quantitatively assessing the effects of a drug on human sperm motility, has been evaluated. The original method has been modified to include a preincubation step, and the incubation time has been reduced to 90 min. In semen samples possessing sperm concentrations of &lt; 75 × 126 spermatozoa mL−1 the volume of the lower reservoir has been reduced to 1 mL. This modified method has been used to compare the spermicidal potency of the widely employed non-ionic surfactant nonoxynol-9, with nonoxynol-5 and nonoxynol-15 (containing, respectively, fewer and more ethylene oxide units per molecule). The rank order of spermicidal potency of the compounds evaluated was nonoxynol-9 = nonoxynol-5 &gt; nonoxynol-15.
Strategy to Assess the Role of (Inter)active Metabolites in Pharmacodynamic Studies In-vivo: a Model Study with Heptabarbital
Authors: Dingemanse Jasper , Thomassen David , Mentink Bert H , Danhof Meindert 
Published: April 2011

Abstract
The purpose of this investigation was to develop a universal experimental strategy by which the role of (inter)active metabolites in in-vivo pharmacodynamic studies can be examined. Heptabarbital was chosen as a model drug and several pharmacokinetic variables which may affect in-vivo concentration-pharmacological response relationships were examined. Adult female rats received an i.v. infusion of the drug at one of three different rates (0.225–1.50 mg min−1) until the animals lost their righting reflex (after 11 ± 1 to 88 ± 8 min of infusion). The serum concentration of the drug at onset of loss of righting reflex (LRR) increased slightly with increasing infusion rate. The drug concentrations in brain tissue and cerebrospinal fluid (CSF), (mean ± s.d.: 67 ± 5 mg kg−1 and 24 ± 4 mg L−1, respectively, for the lowest infusion rate) were not affected by the infusion rate. The possible contribution of (inter)active metabolites to the pharmacological response of heptabarbital was determined by administration of different i.v. bolus doses (14.1–22.5 mg) resulting in widely differing sleeping-times (7 ± 3 to 119 ± 20 min). The concentrations of heptabarbital in serum, brain tissue and CSF at offset of LRR (mean ± s.d.: 77 ± 8 mg L−1, 76 ± 7 mg kg−1 and 29 ± 5 mg L−1, respectively, for the highest dose) were not affected by the administered dose. Kinetic analysis of the relationship between dose and the duration of the pharmacological response revealed an elimination half-life of heptabarbital of 2.8 ± 0.2 h, which is in close agreement with the value determined on the basis of the plasma concentration vs time profile following administration of 22.5 mg i.v. (2.8 ± 0.4 h). In a separate investigation no statistically significant differences were observed in heptabarbital concentrations at onset of LRR during an i.v. infusion (0.563 mg min−1) and at offset of LRR following an i.v. bolus dose (22.5 mg; sleeping time: 100 ± 20 min). These results show that (a) there is a rapid equilibration between the concentrations of heptabarbital (heptabarbitone) in CSF and those at the site of action (i.e. the CSF compartment is pharmacokinetically indistinguishable from the site of action), (b) metabolites do not interfere with the pharmacological effect of heptabarbital and (c) within the time-frame of the experiments there is no development of ‘acute’ tolerance to the anaesthetic effect of heptabarbital. It is concluded that a combination of determination of the concentrations at offset of a certain pharmacological effect following administration of different drug doses, and evaluation of the dose vs duration of pharmacological response relationship, can be a powerful tool in examining the role of unknown (inter)active metabolites.
Cardiovascular Effects of Fibrinopeptide B
Authors: Moore P K , Hussaini I , Bhardwaj R 
Published: April 2011

Abstract
The effect of fibrinopeptide B (FpB) on isolated blood vessels and in the intact rat has been investigated. FpB contracted the rabbit superfused aorta preparation (EC50 = 7.5 nmol) and was some 20 times less potent than noradrenaline. Similarly, FpB (0.2–10 nmol) injected into the rat perfused kidney caused dose related, short-lived increases in perfusion pressure and potentiated the vasoconstrictor effect of injected noradrenaline. These effects were associated with increased efflux of PGE2 (but not TxB2) and were reduced but not abolished by indomethacin (10 μM). FpB injected intravenously into the urethaneanaesthetized rat exhibited vasoconstrictor activity (EC50 = 2.5 μg kg−1) but was less potent than noradrenaline (EC50 = 0.9 μg kg−1). The doses of FpB required to contract the rabbit isolated aorta and to constrict the vasculature of the rat kidney occur naturally in the bloodstream of patients with thrombotic disease. FpB released at the site of thrombus formation may play a part in regulating local blood vessel calibre.
Effect of Levonorgestrel and Ethinyloestradiol on Vasoconstriction in Rat Isolated Vasculature
Authors: Byrne K Bruce , Stanton Bryan J , Coupar Ian M , Burcher Elizabeth 
Published: April 2011

Abstract
Female Sprague-Dawley rats were injected s.c. with 0.2 μg day−1 ethinyloestradiol (EE2) or 2.0 μg day−1 levonorgestrel (NG), procedures previously shown to increase systolic blood pressure. Increases in perfusion pressure to clonidine, phenylephrine, noradrenaline (NA) and angiotensin II (AII) were observed in rat isolated tail arteries, and to NA in the isolated mesenteric vasculature from steroid and vehicle-treated rats. NG treatment for four weeks produced increases in sensitivity to phenylephrine and NA in rat tail arteries; at 6 weeks the increases in sensitivity had largely disappeared but the maximum responses to clonidine and phenylephrine were increased. No change in sensitivity to AII was observed with NG. In contrast, EE2 treatment for six weeks produced increases in sensitivity to AII, and a decrease in sensitivity and maximum response to clonidine but not to phenylephrine or NA, in tail arteries. Responses to NA in the mesenteric vasculature were increased after 6 weeks NG treatment but unaffected after 12 weeks EE2 treatment. It is concluded that NG treatment stimulates α-adrenoceptor number, affinity or receptor-linked Ca2+ events which may contribute to its previously demonstrated hypertensive effect. The increased responsiveness to AII but not the decrease in α2-adrenoceptor responsiveness may be associated with the chronic hypertension induced by EE2.
Cephaloridine resistance in Gram-negative bacteria isolated in Scotland
Authors: Reid Alison J , Simpson Iain N , Harper Paul B , Amyes Sebastian G B 
Published: April 2011

Abstract
The incidence of cephaloridine resistance (minimum inhibitory concentration, MIC &gt; 8mg L−1) in isolates from urinary tract infections was 45.1 % in Glasgow, 22.6% in Dundee and 25.9% in Edinburgh. The incidence of ampicillin resistance (MIC &gt; 8 mg L−1) was even higher:- being 45.2% in Dundee and 48.5% in Edinburgh. In Glasgow, the incidence was 71.9% which is the highest proportion of ampicillin resistance reported in the United Kingdom. The cephaloridine resistant strains were examined for β-lactamase production. Amongst these strains 50.8% produced only a chromosomal β-lactamase, whereas 47.9% produced β-lactamases which were potentially plasmid-mediated on the basis of biochemical tests. Only 1 % of the resistant strains produced no detectable β-lactamase.
Frequency-dependent autoinhibition of histamine release from rat cortical slices: a possible role for H3 receptor reserve
Authors: van der Vliet A , van der Werf I F , Bast A , Timmerman H 
Published: April 2011

Abstract
The inhibition of histamine release after depolarization of rat cerebral cortex slices by electrical stimulation and mediated by the postulated presynaptic autoreceptor (H3) depends strongly on the conditions of stimulation. Using electrically stimulated slices of the cortex a rightwards shift of the concentration-response curve of histamine (an H3 agonist) was observed on increasing the frequency of stimulation. The pA2 value of the H3 antagonist impromidine was, however, not altered at different stimulation frequencies; for a partial agonist only the maximal effect was influenced. These results indicate the existence of a receptor reserve at the H3autoreceptor.
Determination of the Critical Stress Intensity Factor (KIC) of Compacted Pharmaceutical Powders by the Double Torsion Method
Authors: Mashadi A B , Newton J M 
Published: April 2011

Abstract
The critical stress intensity factor KIC has been determined for compacts prepared at different pressures from both Avicel PH101 and sorbitol ‘Instant’, by means of a double torsion method. This method avoids the need for displacement measurement and the introduction of notch into the specimens, both of which present problems with pharmaceutical materials. Measurements of fracture loads for such specimens were reproducible. The values of KIC derived for both materials were found to increase linearly with increase in compaction pressure and linearly with decrease in specimen porosity. Extrapolation of the latter relationship to zero porosity gave values of 1.81 and 0.09 MN m−3/2 for the KIC of Avicel PH101 and sorbitol ‘Instant’, respectively.
Properties of a Semicarbazide-Sensitive Amine Oxidase in Human Umbilical Artery
Authors: Precious Elaine , Lyles Geoffrey A 
Published: April 2011

Abstract
The metabolism of some aromatic amines by amine oxidase activities in human umbilical artery homogenates has been studied. The inhibitory effects of clorgyline showed that 5-hydroxytryptamine (5-HT) and tryptamine, 1 mM, were predominantly substrates for monoamine oxidase (MAO) type A, whereas MAO-A and B were both involved in the metabolism of β-phenylethylamine (PEA), 100 μM, and tyramine, 1 mM. About 20–30% of tyramine and PEA metabolism was resistant to 1 mM clorgyline, but sensitive to inhibition by semicarbazide, 1 mM, indicating the presence of a semicarbazide-sensitive amine oxidase (SSAO). Benzylamine, 1 mM, appeared to be metabolized exclusively by SSAO with a Km (161 μM) at pH 7.8 similar to that found for SSAO in other human tissues. Tyramine and PEA were relatively poor substrates for SSAO, with very high apparent Km values of 17.6 and 13.3 mM, respectively, when determined in the presence of clorgyline, 10−3 M, added to inhibit any metabolism of those amines by MAO activities. However, kinetic studies with benzylamine indicated that clorgyline, 10−3 M, also appears to inhibit SSAO competitively such that the true Km values for tyramine and PEA may be about 60% of those apparent values given above. No evidence for the metabolism of 5-HT or tryptamine by SSAO was obtained. The aliphatic amine methylamine was recently shown to be a specific substrate for SSAO in umbilical artery homogenates. We have used benzylamine and methylamine as SSAO substrates in histochemical studies to localize SSAO in tissue sections. Both amines promoted tissue staining which occurred predominantly over the medial layers of the vessel wall, and this staining was prevented by the presence of semicarbazide, 1 mM, but not by pargyline, 1 mM, in the reaction medium. The results support the notion that smooth muscle cells are an important site of SSAO activity in human blood vessels, and reinforce the possibility that methylamine, an endogenously-occurring amine, may be a better candidate as a physiological substrate for SSAO in man, than several aromatic biogenic amines so far examined.
Effect of tiopronin on prostaglandin synthesis in rabbit kidney medulla slices
Authors: Fujita Tadashi , Fujimoto Yohko , Wada Kohichiro , Kaneko Mika , Sakuma Satoru , Iso Tadashi 
Published: April 2011

Abstract
The effect of 2-mercaptopropionylglycine (tiopronin), which is widely used for the treatment of various hepatic disorders, on the generation of medullary prostaglandins (PG) E2 and F2α has been examined. Tiopronin had a potent inhibitory effect on PG E2 formation. Simultaneously, PG F2α production was increased. In the presence of tiopronin the net increased amount of PG F2α was much smaller than the net decreased amount of PG E2 (6–20%). These results suggest that tiopronin has the potential to modulate PG E2 and F2α synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase and that this effect may represent some pharmacological action of the drug.
Antihistaminic and anticholinergic activities of mequitazine in comparison with clemizole
Authors: Martinez-Mir I , Estañ L , Rubio E , Morales-Olivas F J 
Published: April 2011

Abstract
The antihistamine and anticholinergic properties of mequitazine have been investigated and compared with those of clemizole. Both mequitazine and clemizole antagonized the effect of histamine in guinea-pig ileum competitively, the pA2 values calculated by Schild plot were 9.95 ± 0.44 for mequitazine and 10.54 ± 0.44 for clemizole. Mequitazine at 10−7 M produced a parallel shift of the dose-response curve to acetylcholine in the rat duodenum, clemizole and the lower doses of mequitazine failed to modify the effect of acetylcholine. The potency of mequitazine and clemizole as H1-histamine blockers is similar, but only mequitazine at highest concentration used showed anticholinergic activity.
A comparison of the effects of oxodipine and nifedipine on rat vas deferens
Authors: Martin Isabel , Alfaro Maria José , Tamargo Juan 
Published: April 2011

Abstract
The effects of oxodipine, a new dihydropyridine, were studied and compared with those of nifedipine in the complete vasa deferentia and in the prostatic and epididymal halves of the rat vas deferens. Oxodipine and nifedipine, 10−9–10−6M, produced a dose-dependent inhibition of the contractile responses induced by single pulse stimulation, noradrenaline (3 × 10−5M) and high-K (50 mM). The inhibitory effects of oxodipine were significantly reduced in high Ca media. From these experiments it is concluded that oxodipine, like nifedipine, produced a similar and potent inhibitory effect of the contractile responses induced in the rat vas deferens.