bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interactions of muscarinic drugs with their receptors in single cells of guinea-pig taenia caecum
Authors: Takayanagi Issei , Koike Katsuo , Hiruta Tsuyoshi 
Published: April 2011

Abstract
Single cells were prepared from the guinea-pig taenia caecum and used for the study of drug-receptor interactions. The cells showed a graded response to carbachol, the dose response curve being shifted in a parallel fashion by atropine, indicating a competitive antagonism. The pA2-value of atropine was in agreement with that estimated using the intact tissue. [3H]QNB (quinuclidinyl benzilate) combined with the single cells, the Scatchard plot yielding a straight line. The dissociation constant of QNB was similar to values estimated in other membrane preparations. The apparent dissociation constants of cholinergic drugs estimated from inhibition of the specific binding of [3H]QNB (0.20 nM) to the single cells by the cholinergic drugs were also in agreement with the values in other membrane preparations. The results indicate that the single smooth muscle cells are useful for the study of drug-receptor interactions.
Accumulation of nifedipine after multiple doses
Authors: Lesko L J , Hunter J R , Burgess R C , Rodgers G P 
Published: April 2011

Abstract
The single and multiple dose pharmacokinetics of oral nifedipine capsules, 10 mg, have been examined in five patients with peripheral vasospasm. After a single dose, nifedipine was rapidly absorbed in three and slowly absorbed in two patients. Mean bioavailability parameters included a tmax of 2.9 h, a Cmax of 33.3 ng ml−1 and a AUC0–8 h of 113.3 ngh ml−1. After multiple dosing with either 10 or 20 mg every 8 h for 10 days the mean tmax at steady state was 2.1 h while the mean dose-corrected (to 10 mg) Cmax and AUC0–8 h were 51.9 ng ml−1 and 146.9 ngh ml−1, respectively. The mean elimination rate constant was 0.173 h−1 after both single and multiple doses. The mean extent of accumulation of nifedipine, defined as the ratio of AUC0–8 h (steady state)/AUC0–8 h (single dose), was 1.3; we concluded that nifedipine accumulates in the body when it is administered every 8 h. This should be taken into account when predicting steady state serum concentrations and haemodynamic effects of nifedipine from single dose kinetic data.
Non-ionic surfactant vesicles, niosomes, as a delivery system for the anti-leishmanial drug, sodium stibogluconate
Authors: Baillie A J , Coombs G H , Dolan T F , Laurie J 
Published: April 2011

Abstract
Liver and serum concentrations of antimony in the mouse have been determined after administration of sodium stibogluconate in the free, liposomal and niosomal form. High liver and low serum values were attained by the use of both vesicular formulations. Niosomal sodium stibogluconate was shown to be more active than free drug against experimental murine visceral leishmaniasis, an effect apparently dependent on maintaining high drug levels in the infected reticuloendothelial system.
Diuertic effect of L-threo-3,4-dihydroxyphenylserin, a noradrenaline precursor, in rats and mice
Authors: Katsube Junki , Kato Terufumi , Katsuyama Michiko , Maeda Yukio , Nishikawa Sumiko , Nakamura Mitsutaka 
Published: April 2011

Abstract
L-Threo-DOPS, a noradrenaline (NA) precursor, produced a dose-dependent increase in the volume of urine in mice and rats. It also increased the total output of sodium and chloride ions, but not the excretion of potassium ion. Treatment with peripheral decarboxylase inhibitors antagonized not only the diuretic action, but also the increase in the concentration of kidney NA produced by L-threo-DOPS. These results suggest that the diuretic action of L-threo-DOPS might not be due to its direct action, but largely to NA formed by its decarboxylation in the kidney.
Saliva secretion of chloroquine in man
Authors: Ogubona F A , Lawal A A , Onyeji C O 
Published: April 2011

Abstract
The presence of chloroquine in saliva from seven healthy volunteers for 21 days after a single 600 mg oral dose of the drug was established by chromatographic and spectroscopic methods. The results showed the drug to be rapidly absorbed with a tmax in saliva of 3.9 ± 1.6 h. A long elimination half-life of 7–20 days, calculated from the saliva concentration-time profile, is in agreement with values previously reported for the drug using plasma level data. In three of the volunteers from whom simultaneous blood samples were obtained, the mean Cs/Cp value was 1.20 ± 0.27. It is suggested that saliva level determination may be used in evaluating patient compliance, therapeutic drug monitoring and pharmacokinetic parameters of chloroquine.
Evidence against leukotriene-mediation of propranolol-induced airway hyperreactivity to acetylcholine
Authors: Murlas Christopher 
Published: April 2011

Abstract
In unanaesthetized guinea-pigs, propranolol treatment (0.l mg kg−1 i.v.) substantially increased reactivity to intravenous acetylcholine infusion or aerosolized histamine to a comparable degree. Neither BW755c (5 mg kg−1 i.v.), FPL 55712 (1 mg kg−1 i.v.), nor piriprost (5 mg kg−1 i.v.) pretreatment influenced propranolol's effect on muscarinic reactivity although BW755c abolished histaminic hyperreactivity. This suggests that propranolol-induced muscarinic hyperreactivity in the guinea-pig is not mediated by leukotrienes whereas histaminic hyperreactivity may be.
Tetrodotoxin inhibits directly acting stimulants of intestinal fluid secretion
Authors: Coupar Ian M 
Published: April 2011

Abstract
Intravenous injection of tetrodotoxin (20 μg kg−1) to anaesthetized rats blocks PGE1- and inhibits VIP-induced fluid secretion from the mucosa of the jejunum without affecting the physiological rates of net water and glucose absorption. It is suggested that the toxin might release an endogenous inhibitor of secretion or that it might possess direct antisecretory activity on the epithelial cells of the jejunum. It is further suggested that results where tetrodotoxin has been used to investigate secretagogue action should be treated with caution.
Clonidine reduces plasma melatonin levels
Authors: Lewy A J , Siever L J , Uhde T W , Markey S P 
Published: April 2011

Abstract
Clonidine, an α-adrenoceptor agonist, reduces human plasma melatonin levels when administered intravenously at 2–3 (μg kg−1 to sleeping volunteers. Measurement of plasma melatonin levels after administration of clonidine could be the basis for a clinical in-vivo test of α-adrenoceptors.
Cytochrome P450 metabolic intermediate complex of nefopam
Authors: Leurs R , Donnell D , Timmerman H , Bast A 
Published: April 2011

Abstract
NADPH-catalysed biotransformation of nefopam in liver microsomes obtained from phenobarbitone-pretreated rats leads to the formation of an inactive cytochrome P450 metabolic intermediate (MI) complex. This complex can be detected spectrophotometrically by an absorbance maximum at 459 nm. The extent of the in-vitro MI complexation of 33 μm nefopam, a cyclic analogue of orphenadrine, was almost equal to the extent of the in-vitro MI complexation of 33 μm tofenacine, the mono-N-demethylated metabolite of orphenadrine. The time course of the MI complexation of nefopam and studies with two of its major metabolites suggest an initial biotransformation, which has to occur before MI complexation can take place. Maximal MI complexation of nefopam occurred at approximately 25 μm, whereas the MI complexation could not be detected at 100 μm nefopam.
Effect of pre-existing inflammation on carrageenan-induced paw oedema in rats
Authors: Bhattacharya S K , Das Neeta , Rao P J R Mohan 
Published: April 2011

Abstract
Twenty-four hours after injection of carrageenan into one hind paw, injection of the same amount into the contralateral paw produced a significantly attenuated inflammatory response. However, when the second injection was given 7 days later, the inflammation induced in the contralateral paw was comparable with the initial response to carrageenan. A time-course study of carrageenan-induced inflammation in rats showed that significant oedema persisted 24 h after carrageenan administration and complete recovery was achieved in 7 days. The attenuated inflammatory response in the contralateral paw after 24 h was antagonized by bilateral adrenalectomy and chemical sympathectomy induced by 6-hydroxydopamine. Carrageenan-induced paw oedema was also significantly less in rats with subacute inflammation induced by the croton oil granuloma pouch technique. This attenuated response was antagonized by pretreatment of the rats with metyrapone, an inhibitor of adrenocorticoid synthesis, and by 6-hydroxydopamine. It is likely that the pre-existing acute or subacute inflammation attenuates the inflammatory response of carrageenan, by acting as a stressor, inducing activation of the sympatho-adrenal system.
A study of PAF-induced ocular inflammation in the rat and its inhibition by the PAF antagonist, L-652, 731
Authors: Gautheron P D , Coulbault L , Sugrue M F 
Published: April 2011

Abstract
A significant inflammatory reaction in the rat conjunctiva followed the subconjunctival injection of synthetic platelet activating factor (PAF) in doses which ranged from 10 ng to 1 μg, an inflammatory response being evaluated as the increase in both tissue weight and extravasation of Evans blue dye in the conjunctival tissue. Inflammation was still present 6 h after the injection of 0&#x006d;̇1 μg of PAF. Orally administered indomethacin or BW 755C failed to alter the response to 0&#x006d;̇1 μg of PAF. In contrast, the PAF-induced inflammation was blocked by the oral administration of the PAF receptor antagonist, L-652, 731, a dose as low as 5 mg kg−1 eliciting a significant inhibition. The topical administration of L-652, 731, (two doses of 100 μg as a 1% suspension), elicited a slight, but significant blockade of 23%. Its antagonistic action was more striking when it was co-injected subconjunctivally with 0&#x006d;̇1 μg of PAF, a dose as low as 3 μg evoking a significant blockade. The topical administration of 0&#x006d;̇1 μg of PAF did not elicit a significant inflammatory reaction and this contrasts with the results obtained after its subconjunctival injection.
Penetration of diazepam and the non-peptide CCK antagonist, L-364, 718, into rat brain
Authors: Pullen R G L , Hodgson O J 
Published: April 2011

Abstract
Interest in the actions of the peptide cholecystokinin (CCK) has led to the design and synthesis of several non-peptide CCK antagonists, the most recent being that produced by Merck Sharp & Dohme and designated L-364, 718. This can be viewed as modified D-tryptophan linked to diazepam (1-methyl-3-(2-indoloyl)amino-5-phenyl-3H-1,4-benzodiazepin-2-one) 1.
Intravenous kinetics and metabolism of [15,16-3H]naltrexonium methiodide in the rat
Authors: Misra A L , Pontani R B , Vadlamani N L 
Published: April 2011

Abstract
After a 4 mg kg−1 bolus intravenous dose of [15,16-3H]naltrexonium methiodide to the rat, brain to plasma concentration ratios of the compound were 0.031 to 0.228 between 0.25 to 6 h after injection and the t½β; in plasma and brain were 2.92 and 7.61 h, respectively. Ethyl acetate-extracted radioactivity due to metabolites in plasma decayed with t½β; 1.83 h and the ratios of plasma concentration of metabolites to quaternary compound between 0.25 and 6 h were 0.014–0.026. Only unconjugated 7,8-dihydro-14-hydroxynormorphine, naltrexone and traces of 7,8-dihydro-14-hydroxynormorphinone were the metabolites in plasma. Naltrexone (but not normetabolites) was present only in traces in brain up to 0.5 h after injection and not at later times.
Particulate contaminants of intravenous medications and infusions
Authors: Backhouse C M , Ball P R , Booth Sharon , Kelshaw Margaret A , Potter S R , Mccollum C N 
Published: April 2011

Abstract
Particulate contamination in small volume parenteral medications has been studied and compared with that found in a selection of large volume infusions. Particle counts in 39 commonly used small volume medications and 7 large volume infusions were performed by an automated light blockage method (HIAC) or by optical microscopy. Based on these results and a random survey of drug therapy of intensive care patients, it is concluded that the contribution of intravenous medications to the total particle load received by such patients is likely to be many times greater than from infusion fluids. Until firm evidence regarding the harmful systemic effects of drug particles is available and the manufacturing regulations adjusted appropriately, final in-line filtration of infusions immediately proximal to the intravenous cannula should be considered when drugs are being given intravenously.
Effects of a 5-lipoxygenase inhibitor, REV-5901, on leukotriene and histamine release from human lung tissue in-vitro
Authors: Tennant Carolyn M , Seale J Paul , Temple Diana M 
Published: April 2011

Abstract
REV-5901, α-pentyl-3-(2-quinolinylmethoxy)benzene-methanol, is an arylmethylphenyl ether derivative which inhibits 5-lipoxygenase activity of leukocytes. Its effects on the release of leukotrienes, induced by antigen and calcium ionophore, from human lung tissue in-vitro have been examined. At 1 and 10 μM it significantly inhibited the release of leukotrienes induced by both stimuli. At 10 μM it also inhibited antigen-induced histamine release. These results suggest that REV-5901 may be useful in clinical disorders such as asthma in which leukotriene release may be involved.
Effect of pyridoxine on prostaglandin synthesis in rabbit kidney medulla slices
Authors: Fujimoto Yohko , Nishioka Kazuyuki , Ohtani Noboru , Aihara Midori , Fujita Tadashi 
Published: April 2011

Abstract
Pyridoxine stimulated the generation of prostaglandin E2 in rabbit kidney medulla slices. Moreover, pyridoxine in the presence of aspirin reduced the release of linoleic acid, but enhanced the release of arachidonic acid from the medulla slices as compared with aspirin alone, indicating that the enhancement of prostaglandin E2 formation elicited by pyridoxine may be ascribed to an increased conversion of linoleic acid to arachidonic acid. These results suggest that pyridoxine can be an important modulating factor in prostaglandin synthesis by the kidney.
Differences in the promotion mechanism of the colonic absorption of antipyrine, phenol red and cefmetazole
Authors: SHIGA MASAHARU , HAYASHI MASAHIRO , HORIE TOSHIHARU , AWAZU SHOJI 
Published: April 2011

Abstract
The promotion of antipyrine, phenol red and cefmetazole absorption by sodium ethylenediaminetetraacetate (EDTA-Na) as a paracellular promoter, diethyl maleate (DEM) as a transcellular promoter, and sodium taurocholate (TC-Na), whose promotion mechanism is still unclear, has been investigated by the rat in-situ colonic loop technique. All these promoters increased AP absorption and water influx from the lumen to the blood. Ouabain treatment suppressed the increase in antipyrine absorption and water influx induced by TC-Na and EDTA-Na, but did not modify the enhancing effect of DEM. Thus, the promotion mechanism of TC-Na may be similar to that of EDTA-Na. Phenol red and cefmetazole absorption were increased by TC-Na and EDTA-Na but not by DEM. Accordingly, phenol red and cefmetazole absorption appears to be promoted via paracellular but not transcellular routes. The collection of blood for plasma samples reduced the influx of water which had been increased by TC-Na or EDTA-Na. Consequently, the enhancement in antipyrine plasma concentration by these promoters was reduced to the control level. The inhibitory mechanism for this is discussed on the basis of the blood-flow limitation of antipyrine and water absorption.
Anticholinergic activity of the dopamine receptor agonist, TL-68 (N,N-dipropyl-2-aminotetralin)
Authors: Sahin Inci , Ilhan Mustafa 
Published: April 2011

Abstract
The anticholinergic properties of a dopamine receptor agonist, a non-hydroxylated derivative of N,N-dipropylaminotetralin (TL-68), were evaluated using the guinea-pig isolated tracheal strip and rat phrenic nerve-diaphragm preparations. TL-68 competitively antagonized carbachol-induced contractions in guinea-pig trachea with a pA2 value of 5.88 ± 0.05. In the rat phrenic nerve-diaphragm preparation, TL-68 was found to be inactive in blocking nicotinic cholinergic receptors.
Influence of water deprivation on the disposition of paracetamol
Authors: Zafar N U , Niazi S , Jung D 
Published: April 2011

Abstract
The effect of acute (96 h) water deprivation on the disposition of paracetamol (acetaminophen) has been examined in male Sprague-Dawley rats. Plasma and urinary concentrations of the drug and its two major metabolites, the glucuronide and sulphate, were determined by a sensitive and specific high performance liquid chromatographic assay. Following an intravenous dose of 100 mg kg−1 of paracetamol, no significant changes were found in the elimination rate constant (k), the mean residence time (MRT), total plasma clearance (Cl) and the apparent volume of distribution at steady-state (Vss). However, rats deprived of water for 96 h excreted a larger percentage of the administered dose as the glucuronide conjugate (15.3 vs 7.9%) and a smaller percentage as unchanged paracetamol (7.3 vs 20.7%) in the urine. In addition, there was a significant two-fold increase in the partial metabolic clearance to paracetamol glucuronide. Water deprivation also led to a significant reduction in the renal clearance of paracetamol accompanied by an increase in the renal clearance of the glucuronide.
Influence of time and chloride ions on the interaction of cisplatin with human albumin in-vitro
Authors: Momburg R , Bourdeaux M , Sarrazin M , Chauvet M , Briand C 
Published: April 2011

Abstract
The interaction of cis-dichlorodiammineplatinum (II) (cisplatin) with human serum albumin (HSA), dissolved in phosphate buffer with or without sodium chloride (0&#x006d;̇1 M) has been examined at pH 7&#x006d;̇4 and μ = 0&#x006d;̇154. Equal volumes of cisplatin and HSA solutions were incubated at 37 °C for various times and filterable platinum concentrations versus time measured by flameless atomic absorption spectrophotometry. Binding kinetics differed depending on the buffer solutions used and on the time elapsing between cisplatin dissolution and outset of incubation with HSA. Experimental data were fitted to a theoretical equation used to calculate the number of nucleophilic sites per HSA molecule. Titrations of the HSA sulphydryl group content before and after incubation with a cisplatin solution were made, from which it was shown that the lone SH-group of the HSA macromolecule is involved in cisplatin binding. We also studied HSA's sensitivity towards denaturing agents when it was complexed with cisplatin. This sensitivity was decreased upon cisplatin binding. Also, the binding capacities of HSA and the HSA-Pt(II) complex to both tryptophan and warfarin were compared to determine the possible influence of cisplatin upon the binding to HSA of other drugs; this influence was negligible.
Binding of chlorpromazine, phenytoin and aspirin to the erythrocytes and lipoproteins in whole human blood
Authors: Tamura Akira , Kawase Fumito , Sato Takashi , Fujii Tatsuzo 
Published: April 2011

Abstract
The quantitative binding of 14C-labelled chlorpromazine, phenytoin or aspirin (at 10 μM) to blood cells and plasma lipoproteins in whole human blood or to the washed erythrocytes in an isotonic protein-free medium has been studied. The fractions of chlorpromazine, phenytoin and aspirin bound to the blood cells in whole blood amounted to about 40, 14 and 2% of the total amount added, and those to the lipoproteins amounted to 7, 2 and 1%, respectively. Their binding to the washed erythrocytes in protein-free medium was 95, 76 and 40%, respectively. Their octanol: water partition coefficients were 214, 170 and &lt;0&#x006d;̇1, respectively. These results suggest that the amphiphilic drugs with relatively high hydrophobicity may be bound to the blood cells, mainly to erythrocytes, to considerable extents when administered clinically, and also that their binding to plasma lipoproteins may not be negligible.
The Interaction of Dopexamine with Various Drugs and Excipients in Parenteral Solutions
Authors: Pereira-Rosario Ronald , Utamura Toshiko , Perrin J H 
Published: April 2011

Abstract
The interaction of dopexamine hydrochloride with various excipients and other drugs in parenteral solutions has been investigated by microcalorimetry. The interaction with heparin sodium, in particular, is significant. The interaction is strongest in parenterals containing glucose and is eliminated in normal saline. Divalent cations are more effective than monovalent ones in eliminating the reaction, which is apparently ionic in nature.
Biotransformation of Primary Nicotine Metabolites: Metabolism of R-(+)-[3H-N′-CH3; 14C-N-CH3] N-Methylnicotinium Acetate—The Use of Double Isotope Studies to Determine the In-vivo Stability of the N-Methyl Groups of N-Methylnicotinium Ion
Authors: Pool William F , Crooks Peter A 
Published: April 2011

Abstract
The in-vivo metabolism of R-(+)-[3H-N′-CH3; 14C-N-CH3]-N-methylnicotinium acetate (NMN) was studied in the guinea-pig to determine the in-vivo stability of the N-methyl and N′-methyl groups of this primary nicotine metabolite. The results showed that N-demethylation does not occur. However, losses of 34 and 36%, respectively, of the 3H label in the N′-CH3 group of urinary NMN and the secondary metabolite, N-methyl-N′-oxonicotinium ion (NMNO), were observed. These results suggest that biotransformation of NMN may involve either an initial N′-demethylation step to N-methylnornicotinium ion (NMNor) followed by N′-methylation back to NMN, or the formation of an N′-methylene iminium species, which may be reductively converted back to NMN.
Binding of Amitriptyline to α1-Acid Glycoprotein and its Variants
Authors: Eap C B , Cuendet C , Baumann P 
Published: April 2011

Abstract
Binding studies have been performed between amitriptyline and i) native α1-acid glycoprotein (AAG); ii) its desialylated form; iii) its two variants, S-AAG and F-AAG; and iv) a mixture of S-AAG and F-AAG. Scatchard analysis revealed the presence of two classes of binding sites on AAG. For native AAG, the first class (of high affinity) has an association constant (Ka1) of 1.5 × 106 L mol−1 and a number of binding sites per mole of protein (n1) of 0.25, while the second class (of low affinity) has a Ka2 of 3.2 × 104 L mol−1 and a n2 of 0.94. Similar data were found for desialylated AAG. S-AAG and F-AAG do not differ in their association constants measured with amitriptyline, but in their number of binding sites per mole of protein (n): S-AAG: n1 = 0.56, n2 = 0.52; F-AAG: n1 = 0.17, n2 = 0.71. These results confirm those of a previous study, in which a higher affinity of S-AAG towards various basic drugs in comparison with F-AAG has been found.
Relaxant and β2-adrenoceptor blocking activities of labetalol, dilevalol, amosulalol and KF-4317 on the rat isolated aorta
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
The KCl-contracted rat aorta is relaxed by labetalol, dilevalol, amosulalol and KF-4317. These relaxations are not reversed by ICI 118,551 at 10−6 M and, therefore, are not due to β-adrenoceptor agonism. At 10−7 M, labetalol, dilevalol, amosulalol and KF-4317 were β2-adrenoceptor antagonists as they inhibited the relaxant responses of rat aorta to procaterol.