bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of quinidine on the tissue binding of digoxin in guinea-pigs
Authors: Okudaira Kazuho , Sawada Yasufumi , Sugiyama Yuichi , Iga Tatsuji , Hanano Managu 
Published: April 2011

Abstract
The mechanism of quinidine-induced decrease in the tissue distribution of digoxin to heart, liver and skeletal muscle has been examined in guinea-pigs. Quinidine, in the presence of adenosine-5′-triphosphate (ATP), inhibited the specific binding of digoxin in homogenates of heart, liver and muscle, while in the absence of ATP the inhibition was observed only in heart. The decrease in the tissue-to-plasma unbound concentration ratios (Kpu) of heart and muscle determined from in-vitro binding studies was comparable to that in the Kpu values observed in-vivo, while in liver it was not sufficient to account for the fall in Kpuin-vivo values. It is concluded that quinidine-induced decrease in the tissue distribution of digoxin in heart and muscle is due to inhibition of tissue binding of this drug, while that in liver could be partially attributed to the decrease in the tissue binding.
Mechanisms of the relaxations induced by 5-hydroxytryptamine on the rat isolated caecum
Authors: Uguru Mary O , Bamgbose S O A 
Published: April 2011

Abstract
The mechanism by which 5-HT produces relaxations of the rat caecum has been examined. Propranolol and cocaine markedly attenuated the relaxations whereas tetrodotoxin had no effect. Higher doses of propranolol and cocaine (&gt;10−6 M), as well as reserpinization, converted the relaxations into contractions. There was a residual relaxation resistant to propranolol, cocaine and reserpine treatment. High doses of 5-HT (&gt;10−5 M) were thus thought to relax the rat caecum indirectly, through the release of noradrenaline from the tissue by a tyramine-like action. The relaxations do not seem to be due only to the release of noradrenaline.
Antagonism of non-depolarising neuromuscular blockade by aminopyridines in cats
Authors: Riesz Miklos , Kápáti Egon , Szporny László 
Published: April 2011

Abstract
The antagonism of pipecuronium- and vecuronium-induced neuromuscular blockade by 4-aminopyridine (4AP), 3,4-diaminopyridine (3,4AP) and 3-[(dimethylamino)-carbonyl] amino-4-aminopyridine (LF14) were studied in anaesthetized cats during constant infusion of the relaxants. Aminopyridines were administered cumulatively at steady state 90% block level. The ED50 values of 4AP, 3,4AP and LF14 were 243, 106 and 254 μg kg−1 in pipecuronium, and 232, 195 and 235 μg kg−1 in vercuronium blockade. It has been assumed that in cats the anticurare effect of aminopyridines is mainly a result of K+ channel blockade on motor nerve terminals which enhances the evoked release of acetylcholine.
Relative bioavailability of trimeprazine tablets investigated in man using HPLC with electrochemical detection
Authors: Hu Oliver Y-P , Gfeller Edward , Perrin John H , Curry Stephen H 
Published: April 2011

Abstract
The stability, partition coefficient, plasma protein binding, red blood cell distribution, and whole blood concentrations of trimeprazine were investigated. Trimeprazine solution was stable for 6 months at −20 °C and 3.5 months at 40 °C. In whole blood trimeprazine was stable for 5 weeks at −20 °C., 24 h at 4 °C., 4h at 25 °C and 1 h at 37 °C. The apparent hexane-water partition coefficient varied from 1.50 (at pH 4.83) to over 100 (at pH 10.54). The fraction bound to plasmaprotein exceeded 0.9 as estimated by equilibrium dialysis with correction for volume shift. The mean plasma/red blood cell concentration ratio was 1.17 and the mean red blood cell/plasma distribution coefficient was 8.65. Six healthy adult males received single 5 mg doses of trimeprazine in a syrup (5 mg in 10 ml) and tablets with at least two weeks between doses. Blood was collected for 48 h. The mean (±s.e.m.) times for peak blood concentrations were 3.5 ± 0.22 h for the syrup and 4.5 ± 0.43 h for the tablets. There were no significant differences in Cmax values. The overall mean (±s.e.m.) terminal phase half-life was 4.78 ± 0.59 h. Mean (±s.e.m.) areas under the concentration time curves from 0 to infinity (AUC∞) were 11.0 ± 1.99 ng h−1 ml−1 and 7.67 ± 1.05 ng h−1 ml−1 for syrup and tablets, respectively. The mean relative bioavailability for the tablets was approximately 70% with respect to the syrup.
Evidence that 5-hydroxytryptamine may exert both facilitatory and inhibitory control of electrical field stimulation-evoked contractions in longitudinal muscle taken from the body of guinea-pig stomach
Authors: Gunning S J , Bradbury A J , Costall B , Naylor R J 
Published: April 2011

Abstract
Electrical field stimulation (FS) of guinea-pig stomach body longitudinal muscle strips caused frequency-related contractions mediated via cholinergic mechanisms. Metoclopramide (10−8–10−5 M), MDL 72222 (10−9–10−7 M) and 5-hydroxytryptophan (5-HTP) (3 × 10−7–2.4 × 10−4 M) enhanced these contractions in all tissues, whereas 5-hydroxytryptamine (5-HT) (3 × 10−8–3 × 10−5 M) enhanced the contractions, but only in approximately 15% of the tissues tested. FS-induced contractions were also enhanced in tissues treated in-vitro with p-chlorophenylalanine (2.5 × 10−7–2.5 × 10−5 M) or monofluoromethyldopa (6 × 10−7–10−4 M) or in tissues taken from animals having received p-chlorophenylalanine or monofluoromethyldopa. It is concluded that cholinergic-mediated contractions of stomach strips are subject to 5-HT modulation in two ways. The predominant action of endogenous 5-HT is to exert an inhibitory tone mediated via a metoclopramide and MDL 72222-sensitive 5-HT neuronal receptor. Exogenously applied 5-HT has little overt action to increase the essentially maximal inhibitory action of endogenous 5-HT, but acts on a 5-HT facilitatory receptor system to enhance contractions. Therefore, the actions of 5-HT agonists and antagonists to modify contractions in stomach strips will reflect the balance between 5-HT inhibitory and facilitatory influences, and the specificity of action of the compounds for the two 5-HT receptor systems.
The influence of oxygen tension on theophylline clearance in the rat isolated perfused liver
Authors: Miller Raymond , Oliver Isabel F 
Published: April 2011

Abstract
The effect of changes in the rate of perfusion and oxygen tension (Po2) on theophylline clearance was determined in the rat isolated perfused liver. Changes in rate of perfusion had no effect on the extraction ratio of theophylline while a decrease in the Po2 significantly increased the half life of theophylline. These results suggest that changes in Po2 whether due to disease states or oxygen administration may necessitate theophylline dosage adjustment.
Soluble asparaginase-dextran conjugates show increased circulatory persistence and lowered antigen reactivity
Authors: Wileman Thomas E , Foster Ronald L , Elliott Peter N C 
Published: April 2011

Abstract
Oxidized dextrans of increasing molecular weight were bound covalently to Erwinia carotovora asparaginase. The resulting conjugates retained 50% of their enzyme activity and showed marked resistance to proteolysis by trypsin and chymotrypsin and inactivation by asparaginase-specific antibody. When tested in-vivo, the larger molecular weight conjugates showed prolonged circulatory survival in both immune and non-immune animals and failed to elicit full type III hypersensitivity or anaphylactic reactions when injected into sensitized guinea-pigs. Rabbits could tolerate multiple doses of the asparaginase conjugate without developing an immunity to the enzyme. A conjugate showing increased circulatory half-life and lowered antigen reactivity should have therapeutic potential.
QSAR of binding of dihydropyridine-type calcium antagonists to their receptor on ileal smooth muscle preparations
Authors: Mahmoudian Massoud , Richards W Graham 
Published: April 2011

Abstract
Quantitative structure-activity analysis (Hansch analysis) is applied to elucidate the structural requirement for the binding of dihydropyridine-type calcium antagonists (DHPs) to their receptor in the guinea-pig ileal muscle preparations. It is found that various steric (B1, L), electronic (σ) and hydrophobic (π) parameters or their combinations correlate well with the potency of various DHPs to inhibit the binding of [3H]nitrendipine to the microsomal preparations of the guinea-pig ileal muscle. The potency of DHPs increases with the minimum width (B1) of substituent at ortho- or meta-positions, but decreases with the increase in the length of substituent at the meta-position. The potency of DHPs decreases with the increase in both minimum width or length of substituent at the para-position and the optimal values were found to be those for hydrogen. The hydrophobicity (π) of substituents at different positions in the 4-phenyl ring affects the potency differently, indicating that a different environment exists around each position at the binding site. From the slopes of the π variable in the regression equations, it is concluded that the receptive environment of the ortho-position of the 4-phenyl ring of DHPs is lipophilic, and for that of the para-position hydrophilic. A good correlation is also observed between the Hammett electronic parameter (σ) and biological activity of meta-substituted DHPs. It is suggested that in the binding of the substituted 4-phenyl DHPs to their receptor, both electronic and hydrophobic interactions should be considered.
Solubility of diazepam and prazepam in aqueous non-ionic surfactants
Authors: Moro Manuel E , Velazquez M Mercedes , Cachaza Juan M , Rodriguez Licesio J 
Published: April 2011

Abstract
The solubility of diazepam and prazepam in aqueous polyoxyethylen-10-dodecanol, polyoxyethylen-23-dodecanol and polyoxyethylen-20-hexadecanol, has been determined at 25.0°C. Diazepam seems to achieve a higher micellar penetration than prazepam, in spite of an expected smaller hydrophobic character. Thermodynamic interpretation of the micellar solutions is carried out using the regular solutions approach. A surfactant-independent relation between solubilities of both drugs has been derived.
Preparation of single bilayer liposomes by an electrocapillary emulsification method
Authors: Ishii F , Noro S 
Published: April 2011

Abstract
The single bilayer liposomes have been prepared by an electrocapillary emulsification technique based on interfacial fluctuation in the absence of surfactant. Electron microscopy showed the liposome to be a unilamellar vesicle with a size generally in the range 60–120 nm.
Assessment of acetylcholine release from myenteric plexus of guinea-pig colon
Authors: Trout S J 
Published: April 2011

Abstract
Due to a complex mechanical tissue response to electrical stimulation, a colonic smooth muscle-myenteric plexus (SMMP) preparation, combined with radiolabelling techniques for assessing the acetylcholine release, has been developed to investigate intrinsic cholinergic nerve activity in the guinea-pig colon. Electrical field stimulation of the preparation gave reproducible release of label which was inhibited by tetrodotoxin. Release increased proportionally with the strength of stimulus (130, 150, 195 and 250 mA), but was inversely proportional to frequency of stimulation for a fixed number of pulses, 1 Hz releasing more than 10 Hz. Electrical stimulation of the tissue during incubation with [3H]choline enhanced the release by subsequent field stimulation. Release of label increased progressively towards the distal end of the colon.
Chronic treatment with iprindole reduces immobility of rats in the behavioural ‘despair’ test by activating dopaminergic mechanisms in the brain
Authors: Berettera C , Invernizzi R , Pulvirenti L , Samanin R 
Published: April 2011

Abstract
Iprindole, 10 mg kg−1 i.p., once daily for 21 days, enhanced the metabolism of dopamine in the frontal cortex and striatum of rats with no effect in the nucleus accumbens 1 h after the last injection. Noradrenaline metabolism in the brainstem and telecephalon was also increased in these conditions. No effect on dopamine or noradrenaline metabolism was seen 24 h after the last injection. The same repeated treatment schedule with iprindole markedly reduced the immobility of rats in the behavioural ‘despair’ test 1 h after the last injection and the effect was prevented by 0.5 mg kg−1 i.p. haloperidol and 100 mg kg−1 i.p. sulpiride but not by 3 mg kg−1 s.c. prazosin or 5 mg kg−1 i.p. (±)-propranolol. The data show that enhanced metabolism of brain dopamine and noradrenaline is associated with the presence of iprindole during repeated treatment and the effect on dopamine mechanism is important in iprindole's ability to reduce rats' immobility in the behavioural ‘despair’ test.
Investigations of the solubilization kinetics of binary mixtures of non-polar oils by non-ionic surfactants
Authors: O'Rourke Brian G C , Ward Anthony J I , Carroll Brendan J 
Published: April 2011

Abstract
An investigation of the solubilization kinetics of binary mixtures of non-polar oils by a non-ionic surfactant has been made using the drop-on-fibre technique. Variables studied were the oil composition, surfactant concentration and the temperature. Rates vary linearly with the surfactant concentration for all oil compositions. The observed rate during nearly total solubilization of each oil drop was constant, implying that in these systems solubilization is non-selective. The rates increase as the lower consolute (cloud) temperature of the surfactant is approached. Activation energies of the solubilization process are shown to be independent of the oil composition for the system studied. This suggests that the important stage of the process involves dissociation of the surfactant micelles.
The activity of 25 paroxetine/femoxetine structure variants in various reactions, assumed to be important for the effect of antidepressants
Authors: Plenge Per , Mellerup Erling T , Honoré Tage , Honoré Pierre Le Fèvre 
Published: April 2011

Abstract
Structure-activity relationships for 25 structural variants around the 5-hydroxytryptamine (5-HT) uptake inhibitors paroxetine and femoxetine have been investigated. Three parameters related to the 5-HT system were investigated: (i) The inhibition of [3H]5-HT uptake into rat brain synaptosomes, (ii) the inhibition of [3H]paroxetine binding to rat neuronal membranes and (iii) the effect of the compounds on the affinity of [3H]imipramine for the human platelet membrane binding site, measured as the dissociation rate of the [3H]imipramine human platelet membrane binding site complex. A highly significant correlation was found for 5-HT uptake inhibition and inhibition of [3H]paroxetine binding for the different substances, indicating that the two parameters are closely connected. However the slope of the regression line was only 0&#x006d;̇6 and not 1&#x006d;̇0; this may indicate that [3H]paroxetine binding is necessary, but not sufficient for 5-HT uptake inhibition. No correlation was found between the inhibition of [3H]paroxetine binding and the affinity of the compounds for the [3H]imipramine binding site complex. The two binding sites are therefore probably situated on different parts of the 5-HT transport system, the [3H]paroxetine binding site being part of the 5-HT transport mechanism whereas the [3H]imipramine binding site may represent a site modulating the activity of, and affinity for, 5-HT in the 5-HT transport mechanism. Structure-activity relationships among the substances showed that stereochemical changes from (-)- to (+)-trans changed the activity towards both 5-HT uptake inhibition and [3H]paroxetine displacement for most of the (-)-/(+)-pairs. The substitution of —H with —F or —CH3 also affected the activity. The results showed that in this series of compounds, (-)-trans-4-(p-fluorophenyl)-3-(3,4-methylenedioxyphenoxymethyl)piperidine (paroxetine) is an optimal structure for influencing the chosen parameters.
Effect of triglyceride on small intestinal absorption of cefoxitin in rats
Authors: Yoshitomi Hironori , Nishihata Toshiaki , Frederick Gregory , Dillsaver Margaret , Higuchi Late Takeru 
Published: April 2011

Abstract
Coadministration of trilaurin or monolaurin with sodium cefoxitin increased its absorption from the small intestine of the rat. Its absorption from the rectum was effected to a lesser extent except when lipase was present. Lipase, a natural constituent of the small intestine fluid, may therefore be essential for the adjuvant action of trilaurin on cefoxitin absorption across the intestinal membrane. Among the triglycerides used, trilaurin and tricaprin were the most effective enhancers of cefoxitin absorption. Both the rate of degradation of triglyceride to its fatty acid component and subsequently the rate of fatty acid absorption were factors influencing the enhancing action. Maintenance of fatty acid concentration at the small intestinal absorption site was shown to be necessary to obtain a cefoxitin bioavailability of up to 70%.
The neuromuscular blocking effect of trimetaphan alone and in combination with different non-depolarizing muscle relaxants in the rat
Authors: Pollard B J , Van Der Spek A F L 
Published: April 2011

Abstract
The effect of trimetaphan alone and in combination with pancuronium, tubocurarine or metocurine (dimethyl tubocurarine) has been examined on the rat phrenic nerve diaphragm preparation. Trimetaphan alone produced neuromuscular blockade in an all-or-none fashion once a concentration of between 2&#x006d;̇39 times 10−4 and 3&#x006d;̇00 times 10−4 M had been exceeded. Concentrations of trimetaphan below this threshold produced a dose-dependent potentiation of all three non-depolarizing relaxants studied. This potentiation was equal for tubocurarine and metocurine, but less for pancuronium.
Mandibular and parotid salivary excretion of procainamide and N-acetylprocainamide after intravenous administration of procainamide to rats
Authors: Watanabe Jun , Koyama Ineko , Iwamoto Kikuo , Ozeki Shoji 
Published: April 2011

Abstract
Flow rate, protein level and pH of mandibular and parotid saliva samples in rats were almost stabilized 2h after induction of salivation with pilocarpine (9&#x006d;̇0 mg h−1 kg−1). Salivary excretion profiles of procainamide, 50 mg kg−1 i.v., and its metabolite N-acetylprocainamide (NAPA) were then investigated. Plasma and salivary procainamide levels declined bi-exponentially with time almost in parallel. Salivary procainamide levels (Y) from both types of gland were correlated with the plasma level (X) over a wide concentration range [Y = 0&#x006d;̇108X + 1&#x006d;̇96 (r = 0&#x006d;̇795) for mandibular and Y = 0&#x006d;̇917X (r = 0&#x006d;̇974) for parotid glands]. The mean saliva to plasma concentration ratio (S/P ratio) was significantly higher in parotid (0&#x006d;̇974 ± 0&#x006d;̇243) than in mandibular (0&#x006d;̇284 05119) saliva samples. Similar correlations and S/P ratios were observed for NAPA. Procainamide and NAPA mean S/P ratios for saliva from both glands were fairly consistent with the calculated value according to the pH-partition hypothesis.
Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure
Authors: Gautam P C , Vargas E , Lye M 
Published: April 2011

Abstract
The pharmacokinetics of lisinopril were determined in 6 healthy young, 6 healthy elderly and 6 elderly patients with cardiac failure. Lisinopril (5 mg day−1) was administered for 7 days. Plasma lisinopril concentration was measured at 1, 2, 4, 6, 8 and 24 h on days 1 and 7 of the study. The two elderly groups had higher serum lisinopril concentrations than the healthy young subjects (P &lt; 0&#x006d;̇05). There were no significant differences in any of the areas under the curve (AUC) for lisinopril plasma concentration (over time) between the healthy young and healthy elderly groups. The healthy young patients had AUC values on day 7 lower than elderly patients with cardiac failure (P &lt; 0&#x006d;̇01). Creatinine clearance was correlated wth lisinopril clearance (r = 0&#x006d;̇63; P = 0&#x006d;̇006) and with AUC on day 7 (r = −0&#x006d;̇67; P = 0&#x006d;̇004). Lisinopril clearance was different in the three groups (P &lt; 0&#x006d;̇05): healthy young patients had the highest and elderly patients with cardiac failure the lowest values. Thus, in the elderly a reduced renal clearance of lisinopril leads to higher and more sustained blood levels. In elderly patients with cardiac failure, renal function should be estimated before lisinopril is prescribed as a reduction in dose may be appropriate.
Influence of pH on the buccal absorption of morphine sulphate and its major metabolite, morphine-3-glucuronide
Authors: Al-Sayed-Omar O , Johnston A , Turner P 
Published: April 2011

Abstract
Buccal absorption of morphine sulphate and morphine-3-glucuronide at various buffer pH values (4 to 10) over 5 min has been investigated in seven and four normal healthy volunteers, respectively. Increasing pH caused an increase in buccal absorption of both. The maximum mean absorption was 37% at pH 10 for morphine and 19% at pH 8 for morphine-3-glucuronide.
The separation of unbound prednisolone in plasma by centrifugal ultrafiltration
Authors: Miller P F W , Wheeldon J , Brocklebank J T 
Published: April 2011

Abstract
To study variable plasma protein binding of prednisolone in children with nephrotic syndrome we have devised a simple rapid method for measuring unbound prednisolone. The plasma was initially ultrafiltered at 37°C in a 35° fixed angle head at 1500 g for 30 min then the filtrate was analysed by high pressure liquid chromatography. The effects of variable ultrafiltration conditions were studied. The method was used to compare the AUC unbound prednisolone in a nephrotic child (plasma albumin concentration 18 g L−1) with a control (plasma albumin concentration 43 g L−1); their respective AUC unbound prednisolone values were 4.02 mg h L−1 and 1.07 mg h L−1.
Effect of trimethoprim, paracetamol and cimetidine on trimetrexate metabolism by rat perfused isolated livers
Authors: Webster Lorraine K , Tong William P , McCormack John J 
Published: April 2011

Abstract
Trimetrexate (TMTX), a non-classical antifolate, is currently in clinical trial as an antineoplastic drug. In the rat perfused isolated liver, it undergoes extensive metabolism to two metabolites, M1 and M2, which are excreted primarily in the bile. The metabolites result from demethylation, and M1 is also glucuronidated. We examined the effects of three commonly used drugs on the elimination of 1 mg of TMTX by the rat perfused isolated liver (perfusate volume was 100 mL). Co-administration of either 1 or 5 mg cimetidine, a well-known inhibitor of microsomal oxidation, caused an increase in TMTX terminal elimination half-life (69 and 100% at 1 and 5 mg, respectively) and a decrease in clearance (40 and 46% at 1 and 5 mg, respectively). Paracetamol (acetaminophen) was chosen for a possible interaction with TMTX because its major metabolic pathway is glucuronidation. Five mg paracetamol resulted in no change in TMTX pharmacokinetics, but M1 concentrations were increased by 72% in bile, and M2 was not present in perfusate. The third drug tested was trimethoprim, which has some structural similarities to TMTX; however, no effects were noted on the levels of TMTX, M1 or M2 after 1 mg trimethoprim. These results indicate that TMTX elimination can be inhibited by cimetidine, probably due to competition for microsomal enzymes, and that paracetamol may alter the metabolite profiles; trimethoprim had no effect on TMTX disposition under the conditions employed.