bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation Between Structures of Organic Cations and Their Binding Behaviours to Brush Border Membrane Isolated from Rat Small Intestine
Authors: Saitoh Hiroshi , Noujoh Akiko , Chiba Yukihiro , Iseki Ken , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
We have investigated the correlation between the molecular structures of various organic cations and their binding to rat small intestinal brush border membrane. The binding of small quaternary ammonium compounds such as tetramethylammonium and choline to brush border membrane was not sufficient to inhibit methylchlorpromazine binding. However, lauryltrimethylammonium and cetyltrimethylammonium, both quaternary amines with a long carbon chain, inhibited binding significantly. The inhibition was competitive. When the unbranched hydrocarbon chain of the quaternary amines was extended in steps from C1 (methyl) to C16 (cetyl), the inhibitory effect increased sharply with length from C7 (heptyl) to C16. These results suggest that the size of the hydrophobic part of the molecule is an important factor in binding of quaternary ammonium compounds to the brush border membrane. The structure of the hydrophilic part was another factor. In imipramine-related compounds, the order of binding was N-didesmethylimipramine (primary amine) &gt; desipramine (secondary) &gt; imipramine (tertiary) &gt; methylimipramine (quaternary). However, with the small molecular ethylamine-related compounds, binding properties did not reflect differences in the hydrophilic component. Therefore, the effect of the hydrophilic part may be secondary and may depend on the size of the hydrophobic part. We suggest that organic cations which are amphiphilic can bind to a common binding site on brush border membrane through hydrophobic and/or hydrophilic interactions.
Contribution of Passive Transport Mechanisms to the Intestinal Absorption of β-Lactam Antibiotics
Authors: Sugawara Mitsuru , Saitoh Hiroshi , Iseki Ken , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
The transport characteristics of aminopenicillins (ampicillin and amoxicillin), aminocephalosporins (cephalexin, cephradine and cefadroxil) and cefazolin have been compared with those of an actively transported substance (D-glucose) and a passively transported substance (L-glucose). Although the initial uptake of the aminocephalosporins was stimulated in the presence of an inward H+ gradient, there was no overshoot in the uptake of any of the drugs tested, even in the presence of an H+ gradient. Also, the time course and the degree of uptake of these drugs were similar to those of L-glucose, especially in the absence of an H+ gradient. These results suggest that the β-lactam antibiotics tested, like L-glucose, pass through the rat intestinal brush border membrane mainly by passive diffusion. However, the differences in absorption between these drugs, like the differences in their disappearance from a proximal loop of rat intestine, cannot be explained by a simple permeation process alone.
The Effects of (±)-, (+)- and (-)-Celiprolol and Bromoacetylalprenololmentane at the β-Adrenoceptors of Rat Isolated Cardiovascular Preparations
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
The effects of (±)-, (+)- and (-)-celiprolol and of bromoacetylalprenololmentane (BAAM, an irreversible β-adrenoceptor antagonist) on the contractile responses of the electrically driven rat right ventricle strip to isoprenaline and on the relaxant responses of the rat aorta to procaterol, have been studied. Racemic and (-)-celiprolol or BAAM treatment of the ventricle produced non-parallel rightward shifts of the isoprenaline response curves with a reduction in the maximal response. Sotalol produced parallel rightward displacements of the procaterol response curves of the aorta with no effect on the maximal relaxations. Racemic and (+)- and (-)-celiprolol or BAAM treatment of the aorta produced non-parallel rightwards shifts of the procaterol relaxant curves with a reduction in the maximal relaxation. The BAAM data was used to demonstrate that the KA (dissociation constant) for isoprenaline at β1-adrenoceptors was 1.46 × 10−7 M and for procaterol at β2-adrenoceptors was 2.34 × 10−5 M. Calculation of receptor occupancy demonstrated that to produce a maximal response of the rat right ventricle, isoprenaline had to occupy 87% of the β1-adrenoceptors. Likewise, for a maximal response of the rat aorta, procaterol had to occupy 81 % of the β2-adrenoceptors. It is suggested that the use of tissues with small β-adrenoceptor reserves has shown that (±)- and (-)-celiprolol are slowly dissociating, rather than readily reversible, β-adrenoceptor antagonists.
The effect of loperamide oxide on prostaglandin-stimulated fluid transport in rat small intestine
Authors: Hardcastle J , Hardcastle P T , Goldhill J 
Published: April 2011

Abstract
The effects of loperamide and loperamide oxide on basal and prostaglandin Erstimulated fluid transport by rat small intestine have been investigated. In contrast to loperamide, loperamide oxide, when applied intraperitoneally, failed to inhibit either basal or prostaglandin E2-stimulated fluid transport. However, intraperitoneal administration of loperamide oxide following its incubation with the contents of the intestinal lumen under aerobic conditions resulted in an effective inhibition of fluid secretion. The activating material was present in the essentially non-particulate 3000 g supernatant fraction of the luminal contents and was heat-stable.
Endothelin action on goat cerebral arteries
Authors: Vila J M , de Aguilera E Martin , Martinez M C , Rodriguez M D , Irurzun A , Lluch S 
Published: April 2011

Abstract
Cumulative application of endothelin-1 (human) markedly constricted goat isolated cerebral arteries in a concentration-dependent manner. Contractile responses were not affected by removal of endothelial cells. Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−7 M) failed to abolish responses to endothelin. The results suggest that the endothelium-independent constriction of cerebral arteries produced by endothelin cannot be explained solely by voltage-dependent calcium channels. The contractile responses are likely to be mediated by stimulation of specific receptors for this peptide.
Calcium Antagonist Properties of Cinnarizine, Trifluoperazine and Verapamil in Guinea-pig Normal and Skinned Trachealis Muscle
Authors: Cortijo J , Foster R W , Small R C , Morcillo E J 
Published: April 2011

Abstract
In guinea-pig trachealis, depolarized by a K+ -rich medium, Ca2+ (0.01–10 mM) caused concentration-related spasm. Verapamil (0.5-5 μM), cinnarizine (10–100 μM) and trifluoperazine (16–160 μM) each produced concentration-dependent antagonism of Ca2+ characterized by a rightward and downward displacement of the log concentration-effect curve for Ca2+. The rank order of potencies of these antagonists, measured as the IC75 against Ca2+ (10 mM)-induced contraction of depolarized trachea, was verapamil (5.6 μM) &gt; cinnarizine (59 μM) &gt; trifluoperazine (91 μM). In skinned trachea, verapamil in concentrations up to 100 μM did not modify the concentration-effect curve for Ca2+. In contrast, cinnarizine (59–177 μM) diminished the sensitivity and trifluoperazine (273 μM) decreased the responsiveness of the tissue to Ca2+. In skinned trachea, trifluoperazine (91 μM) produced greater inhibition of Ca2+ (10 μM)-induced contraction after 120 min than after 30 min of incubation. Verapamil (100 μM) and cinnarizine (177 μM) were devoid of inhibitory effect against the 10 μM Ca2+ standard. In skinned trachea, changes in the Ca2+ concentration-effect curve produced by cinnarizine (177 μM) were reversed after washout whilst those induced by trifluoperazine (273 μM) persisted. It is concluded that distinct differences exist between the three calcium antagonists examined. The action of verapamil is restricted to the plasmalemma. That of cinnarizine and trifluoperazine is exerted both on the plasma membrane and upon the intracellular contractile machinery.
The Effect of Malaria Infection on the Disposition of Quinine and Quinidine in the Rat Isolated Perfused Liver Preparation
Authors: Mansor S M , Ward S A , Edwards G , Hoaksey P E , Breckenridge A M 
Published: April 2011

Abstract
The effect of malaria on the disposition of quinine and quinidine was studied in livers isolated from young rats infected with merozoites of Plasmodium berghei, a rodent malaria model, and non-infected controls. Following bolus administration of quinine (1 mg) or quinidine (1 mg) to the 100 mL recycling perfusion circuit, perfusate was sampled (0–4 h) and plasma assayed for quinine and quinidine by HPLC. Higher quinine (AUC: 6470 ± 1101 vs 3822 ± 347 ng h mL−1, P &lt; 0.001) and quinidine (AUC: 6642 ± 1304 vs 4808 ± 872 ng h mL−1, P &lt; 0.05) concentrations were observed during malaria infection (MI). MI resulted in decreased quinine clearance (CL) (0.33 ± 0.08 vs 0.64 ± 0.09 mL min−1 g−1, P &lt; 0.001) and volume of distribution (Vd) (53.0 ± 13.3 vs 81.2 ± 23.7 mL g−1, P &lt; 0.05) but no significant change in elimination half-life (t1/2) (1.93 ± 0.6 vs 1.37 ± 0.25 h, P &gt; 0.05). With quinidine, however, MI resulted in decreased CL (0.38 ± 0.16 vs 0.64 ± 0.09, P &lt; 0.05) with no change in Vd and a significant increase in t1/2 (1.62 ± 0.42 vs 0.88 ± 0.22, P &lt; 0.01). In summary, the hepatic disposition of quinine and quinidine is altered in the malaria-infected rat.
JO 1784, a potent and selective ligand for rat and mouse brain σ-sites
Authors: Roman François J , Pascaud Xavier , Martin Brigitte , Vauché Daniel , Junien Jean-Louis 
Published: April 2011

Abstract
JO 1784 ((+)-cinnamyl-1-phenyl-1-N-methyl-N-cyclopropylene) is a potent ligand for (+)-[3H]SKF 10,047 (2′-hydroxy-5,9-dimethyl-2-allyl-6,7-benzomorphan) binding sites in rat brain membrane preparations with an IC50 of 39 ± 8 nM, which is comparable to that of haloperidol. The stereoisomer of JO 1784 is ten fold less potent. When administered to mice i.p. or p.o. JO 1784 displaced (+)-[3H]SKF 10,047 (5 μCi i.v.) from its sites in the brain with ID50 values of 1.2 and 3.5 mg kg−1, respectively. The high selectivity of JO 1784 for the σ-binding site was assessed by its lack of significant affinity for more than 20 other sites including those for phencyclidine.
Comparison of the inhibitory action of aminobeclamide and beclamide on socially offensive behaviour
Authors: Darmani N A , Sewell R D E , Hasan M Y , Nicholls P J 
Published: April 2011

Abstract
The inhibitory effects of aminobeclamide (N-(p-aminobenzyl)-β-chloropropionamide) on socially offensive behaviour has been studied and compared with those of the parent drug beclamide (N-benzyl-β-chloropropionamide). Following oral administration in mice which had been individually housed for a 28 day period then paired with normal group-housed opponents, aminobeclamide and beclamide both produced significant and dose-related inhibition of socially offensive behaviour. Aminobeclamide (20–150 mg kg−1 p.o.) and beclamide (50–250 mg kg−1 p.o.) gave increased offense onset latency whilst at the same time they reduced the incidence of offense encounters/animal and decreased the group percentage of animals displaying offense behaviour. It is likely that both drugs have similar monoamine modifying effects though this animal study suggests that aminobeclamide is 1.5 to 2.7 times more potent than beclamide against socially offensive behaviour.
A rapid gas-liquid chromatographic method for the determination of cotinine and nicotine in biological fluids
Authors: Feyerabend C , Russell M A H 
Published: April 2011

Abstract
A rapid method is described for the simultaneous measurement of nicotine and cotinine in biological fluids using capillary column gas-liquid chromatography. Using 100 μL sample volume the lower limit of detection for both nicotine and cotinine was 100 pg mL−1, allowing the method to be used for the measurement of these compounds in both smokers and non-smokers. The extraction time is 3 min per sample, and by using multi-pipetting and vortexing systems 250 samples can be extracted per day. The average coefficient of variation over the nicotine range 10 to 100 ng mL−1 was 3.9% and for cotinine over the range 1.0 to 1000 ng mL−1 was 2.2%. Saliva cotinine concentrations were quantitatively related to passive exposure to parental smoking in a population study of 1118 non-smoking schoolchildren.
Pre- and Post-junctional α-Adrenoceptor-mediated Responses in the Rat Gastric Fundus In-vitro
Authors: MacDonald A , Kelly J , Dettmar P W 
Published: April 2011

Abstract
The effects of α1-and α2-adrenoceptor agonists on smooth muscle tone and on cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory responses to field stimulation have been investigated in the rat gastric fundus in-vitro. None of the α-adrenoceptor agonists tested, noradrenaline, phenylephrine, cirazoline, guanoxabenz or UK-14,304 showed any contractile effects at concentrations up to 30 μM. In preparations where tone was raised by barium (0.5-2 mM), the mixed α1-and α2-adrenoceptor agonist noradrenaline (0.01–10 μM), and the selective α1-adrenoceptor agonists cirazoline (0.01–10 μM) and phenylephrine (0.01–10 μM) produced concentration-dependent relaxations which were antagonized by the α1-adrenoceptor antagonist prazosin (0.01-1.0 μM). The selective α2-adrenoceptor agonists UK-14,304 (0.03–30 μM) and guanoxabenz (0.03–30 μM), had no relaxant effects in raised tone. UK-14,304 (0.03-1.0 μM) produced a concentration-dependent inhibition of cholinergic nerve-induced responses which was antagonized by the α2-adrenoceptor antagonist idazoxan (0.03-1.0 μM) but not by prazosin (0.03-1.0 μM). Noradrenaline (0.03-1.0 μM) also produced an inhibition of cholinergic nerve-induced responses which was antagonized by idazoxan (0.03–10 μM). A small component of the noradrenaline inhibitory effects was antagonized by prazosin (10%). Cirazoline (0.03-1.0 μM) produced a small inhibition of cholinergic nerve-induced responses which was antagonized by prazosin (0.03-1.0 μM). The prazosin-sensitive components of the inhibitory effects of noradrenaline and cirazoline occurred at concentrations which also produced post-junctional relaxation. UK-14,304 (0.03-1.0 μM) also attenuated non-adrenergic, non-cholinergic (NANC) inhibitory nerve-induced responses and this effect was antagonized by idazoxan (0.03-1.0 μM). The effects of α1-adrenoceptor agonists on NANC nerve-induced responses proved difficult to assess since these agonists caused post-junctional relaxation which itself reduced the size of the inhibitory nerve-induced responses. It is concluded that α-adrenoceptor mediated responses in the rat gastric fundus in-vitro consist of post-junctional α1-adrenoceptor-mediated relaxation of the smooth muscle and pre-junctional α2-adrenoceptor-mediated inhibition of both cholinergic excitatory and non-adrenergic, non-cholinergic inhibitory nerve-induced responses.
Impairment of Endothelium-dependent Relaxation and Changes in Levels of cyclic GMP in Carotid Arteries from Stroke-prone Spontaneously Hypertensive Rats
Authors: Miyata Noriyuki , Tsuchida Katsuharu , Tanaka Makoto , Otomo Susumu 
Published: April 2011

Abstract
Endothelium-dependent relaxation of carotid arteries and changes in levels of cyclic (c)GMP between stroke-prone spontaneously hypertensive (SHRSP) and Wistar-Kyoto (WKY) rats have been compared. The concentration-response curve for acetylcholine (ACh)-induced relaxation was shifted to the right in carotid arteries from SHRSP. Relaxation responses produced by calcimycin (A 23187) and melittin, both endothelium-dependent agents, were depressed in carotid arteries from SHRSP. Relaxation responses produced by sodium nitroprusside and 8-Br-cGMP were similar to those in strips from WKY. ACh-induced production of cGMP was significantly decreased in carotid arteries from SHRSP when compared with the level for similarly treated strips from WKY. These results suggest that functional changes in endothelium, but not guanylate cyclase activity or cGMP sensitivity in the carotid arteries, may occur in hypertension. Thus, impaired endothelium-dependent relaxation in SHRSP may play an important role in hypertensive vascular diseases such as stroke.
Anti-allergic Effect of N-Acetylneuraminic Acid in Guinea-pigs
Authors: Kai Hirofumi , Murata Yoshiyuki , Ishii Takayuki , Nishijima Sachiko , Murahara Koichiro , Ogasawara Sadanori , Sugiyama Naokazu , Takahama Kazuo , Miyata Takeshi 
Published: April 2011

Abstract
The in-vivo anti-allergic effect of N-acetylneuraminic acid (NANA) in guinea-pigs passively sensitized with anti-ovalbumin rabbit serum has been studied. NANA (20 mg kg−1 i.v.) inhibited bronchial anaphylaxis and the release of histamine into bronchoalveolar lavage fluid. NANA dose-dependently inhibited heterologous passive cutaneous anaphylaxis and haemorrhaging in the passive Arthus reaction. However, it did not inhibit the release of histamine from sensitized minced lung tissue.
Cut-off Effect in Antimicrobial Activity and in Membrane Perturbation Efficiency of the Homologous Series of N,N-Dimethylalkylamine Oxides
Authors: Devínsky Ferdinand , Kopecka-Leitmanová Anna , Šeršeň František , Balgavý Pavol 
Published: April 2011

Abstract
The antimicrobial activity of the homologous series of N,N-dimethylalkylamine oxides (DMAO) was found to be quasi parabolically dependent on alkyl chain length with a maximum at n ∼ 15 and n ∼ 12 for Staphylococcus aureus and Escherichia coli, respectively. The physicochemical properties of DMAOs as characterized by critical micelle concentrations, retention times of 1-alkenes generated from DMAOs by gas-liquid chromatography, Rm values in reversed phase chromatography, and bacterial lipid/aqueous phase partition coefficients were found to correlate with the alkyl chain length. The effect of DMAOs on the structure of the model membrane prepared from isolated lipids from Escherichia coli as detected by a spin probe method was maximal for the alkyl chain length n ∼ 10–12 coinciding with the maximum in the antimicrobial activity observed with Escherichia coli. It is suggested that the cut-off in the DMAO antimicrobial activity is caused by the cut-off in the DMAO perturbing effect on the membrane structure.
Synthesis and resolution of the novel appetite suppressant 2-benzylmorpholine, a nonstimulant isomer of phenmetrazine
Authors: Brown George R , Forster Gillian , Foubister Alan J , Stribling Donald 
Published: April 2011

Abstract
The synthesis of 2-benzylmorpholine from allylbenzene together with its resolution into its (+)-and (—)-enantiomers is reported. Oral dosing of the racemate to dogs caused appetite suppression with an ED50 of 3 and 5.5 rag kg−1 at I and 2 h, respectively, after access to a meat meal. No stimulant activity was observed in dogs given oral doses of 200 mg kg−1 but the appetite suppressant effect in dogs declined during 20 days of chronic oral dosing at 10 mg kg−1. Appetite suppression activity was shown to reside in the (+)-enantiomer.
The effect of cigarette smoke on the plasma piroxicam concentrations in rats
Authors: Lermioǧlu Ferzan , Berkan Tayfun , Yasa Mukadder , Kerry Zeliha , Yalçinkaya Cengiz , özer Asli 
Published: April 2011

Abstract
The plasma concentration of unchanged piroxicam has been determined at 15, 30, 60 and 90 min after 10 mg kg−1 oral administration of the drug to rats exposed to cigarette smoke or pretreated with phenobarbitone, 3,4-benzpyrene or ethanol. Plasma piroxicam concentrations decreased in rats pretreated with phenobarbitone, 3,4-benzpyrene and ethanol and in rats 24 h after exposure to cigarette smoke.
The binding of physostigmine to human serum albumin
Authors: Whelpton Robin , Hurst Peter R 
Published: April 2011

Abstract
The binding of [3H]physostigmine to crystallized human serum albumin (HSA) has been investigated using equilibrium dialysis. The percentage bound to 1% (w/v) HSA decreased from 18 to 4% as the total concentration of physostigmine increased from 3.3 nM to 2.7 μM (0.9 to 750 ng mL−1). A single class of specific binding sites with a large affinity constant, K = 8 × 107 L mol−1, was identified. The concentration of binding sites was approximately 3 nM. The Michaelis constants for human serum cholinesterase and albumin were the same; an explanation for these results is that the drug is binding to a trace cholinesterase, in the albumin.
Plasma protein binding of disulfiram and its metabolite diethylthiocarbamic acid methyl ester
Authors: Johansson Benny 
Published: April 2011

Abstract
The human plasma protein binding of disulfiram and its metabolite, diethylthiocarbamic acid methyl ester has been studied by an ultrafiltration technique. Both compounds were bound principally to albumin (mean 96.1 and 79.5%) over the ranges 200–800 and 345–2756 nM, respectively. The average number of binding sites was approximately 1 for both substances, whereas the average association constants were 7.1 × 104 and 6.1 × 103 M−1, respectively. Log P (octanol/water) was 2.81 for disulfiram and 1.85 for diethylthiocarbamic acid methyl ester.
Influence of the method of Fluosol-DA administration on antipyrine metabolism in the rat
Authors: Shrewsbury Robert P , White Lisa G 
Published: April 2011

Abstract
Antipyrine disposition has been determined in the rat following administration of Fluosol-DA by an intravenous infusion without blood removal or a haemodilution procedure, and compared with data from sham haemodiluted rats (blood removed and returned) and control rats which only received antipyrine. Antipyrine total body and renal clearance and the formation clearance of two of its metabolites were affected differently at 48 h by the pretreatments. The haemodilution procedure enhanced, the sham haemodilution reduced, and the intravenous infusion had no effect on the phenobarbitone inducible cytochrome P450 isoenzyme activity.
Effects of Solvents and Detergents on the Contractions of Isolated Smooth Muscle Preparations
Authors: Braak Klaus , Frey Hans-Hasso 
Published: April 2011

Abstract
In testing poorly soluble substances in-vitro on isolated organs, organic solvents and solubilizers are used to increase water-solubility. To facilitate selection of appropriate substances, the effects of eleven of these chemicals have been studied in the following isolated smooth muscle preparations: guinea-pig ileum stimulated by carbachol, histamine, 5-HT or single field stimuli; rat fundus stimulated by 5-HT; and mouse vas deferens stimulated by noradrenaline or trains of field stimuli. Nine solvents (acetone, diethyleneglycol monoethylether, dimethyl sulphoxide, ethanol, glycerol, methanol, polyethylene glycol 400, 1,2-propanediol, Tetraglycol (tetrahydrofurfurylalcohol polyethyleneglycolether)) and two detergents (Triton-X 100 and Tween 80) were examined. The vas deferens proved to be most resistent, whereas rat fundus and guinea-pig ileum were more sensitive to the effects of solvent when present from 1 to 10 g L−1. Most solvents caused non-specific, concentration-dependent reversible inhibition of contractions. Dimethyl sulphoxide in high concentrations increased the contractile responses of guinea-pig ileum stimulated by 5-HT and in both experiments with electrical stimulation. Polyethylene glycol 400 augmented the response of mouse vas deferens to electrical stimulation. Overall, 1,2-propylene glycol and polyethylene glycol 400 had the least effect and can be used in a concentration of 3 g L−1, and in qualitative studies even up to 10 g L−1. Glycerol, both monohydric alcohols and dimethyl sulphoxide produced more intense effects and should not exceed concentrations of 1–3 g L−1. Stronger inhibition was caused by diethyleneglycol monoethylether, acetone and Tetraglycol, and the bath concentrations of these substances should not exceed 0.5-lg L−1. Of the detergents only Tween 80 is suitable as a solubilizer in smooth muscle preparations in-vitro, forming micelles at 10 mg L−1 a concentration tolerated by isolated organs in this study.