bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Pinacidil on the Electrophysiological Properties in Guinea-pig Papillary Muscle and Rabbit Sino-atrial Node
Authors: Hirai Shozo , Kotake Hiroshi , Kurata Yasutaka , Hisatome Ichiro , Hasegawa Junichi , Mashiba Hiroto 
Published: April 2011

Abstract
The electrophysiological effect of the antihypertensive drug pinacidil has been examined in preparations of guinea-pig papillary muscle and rabbit sino-atrial node using a standard microelectrode method. In papillary muscle preparations, pinacidil (&gt; 30 μM) shortened the action potential duration (APD), whereas it did not affect the maximum rate of rise (Vmax). Pinacidil (&gt; 1 μM) also decreased APD of slow action potentials evoked by high K+ (27 mM) solution containing 0.2 mM Ba2+. At 30 μM, the drug reduced the Vmax of slow action potentials. In the spontaneously beating sino-atrial node, pinacidil (&gt; 30 μM) shortened APD. At 100 μM, it also decreased the heart rate, Vmax, action potential amplitude and the rate of diastolic depolarization. It is concluded that pinacidil modifies the electrical activity of myocardial cells probably due to an increase in the potassium conductance although in high concentrations the compound might also reduce Ca2+ influx through the cell membrane, which would contribute to an obvious negative chronotropic action.
The effect of an antacid and food on the absorption of cimetidine and ranitidine
Authors: Desmond P V , Harman P J , Gannoulis N , Kamm M , Mashford M L 
Published: April 2011

Abstract
The effect of varying doses of a liquid antacid preparation containing magnesium hydroxide, aluminium hydroxide and simethicone on the absorption of the H2-receptor antagonists, cimetidine and ranitidine, was determined in 2 groups of 11 volunteers; one group fasted and one group fed a standardized breakfast. The antacid alone caused a significant decrease in the AUC of cimetidine (24%). Similarly, concomitant antacid caused a 59% decrease in the AUC of ranitidine. There were no effects on any of the other pharmacokinetic parameters examined. The absorption of both drugs was similar in fasted and fed volunteers, but in the fed volunteers the antacid did not produce the decrease in AUC seen in the fasted volunteers. These data suggest that H2-receptor antagonists should not be taken at the same time as antacids.
The selectivity of the opioid antagonist, naltrindole, for δ-opioid receptors
Authors: Rogers Helen , Hayes Ann G , Birch Philip J , Traynor John R , Lawrence Andrew J 
Published: April 2011

Abstract
In the mouse vas deferens, naltrindole gave pKB values of 9.7, 8.3, and 7.5 at the δ-, μ-, and K-sites and in binding assays, pIC50 values of 9.6, 7.8 and 7.2 at the same sites. The affinity of naltrindole for the δ binding site was increased in the presence of sodium ions and 5′-guanylylimidophosphate. Naltrindole is, thus, a potent opioid antagonist with marked selectivity for the δ-opioid receptor.
Suppression of ventricular arrhythmias resulting from acute coronary artery ligation in rat by imipramine
Authors: El-Mahdy Samiha A M , Alhaider A A , Mahgoub Afaf A , Bashandy Abdulwahab M 
Published: April 2011

Abstract
The potential antiarrhythmic activity of imipramine against ventricular arrhythmias induced by coronary artery ligation in rats has been investigated and compared with procainamide. Imipramide (1 and 5 mg kg−1) or procainamide (5 and 10 mg kg−1) or solvent were injected intravenously 30 min before ligation. Imipramine reduced the total number of ventricular ectopic beats as well as the incidence and duration of ventricular tachycardia and ventricular fibrillation. The drug did not significantly affect the blood pressure but reduced the heart rate. The antiarrhythmic activity of imipramine is postulated to be due to a quinidine-like effect and/or α-adrenergic blocking activity. The study confirms the potential utility of imipramine as an antiarrhythmic drug.
Some Differential Effects of 4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine Hydrochloride on Guinea-pig Atria and Ileum
Authors: Barlow R B , Shepherd M K , Veale M A 
Published: April 2011

Abstract
4-Diphenylacetoxy-N-(2-chloroethyl)-piperidine hydrochloride (I) cyclizes at neutral pH to form an aziridinium salt. The formation and breakdown of the salt depend on the temperature (in the range 25 to 37°C). In solution at 30 C., peak levels, corresponding to 60–80% conversion, are reached after around 60 min and the half-life exceeds 100 min. In the presence of 0.9% NaCl conversion was reduced to 45–60%. I blocks muscarinic receptors in guinea-pig ileum and atria irreversibly and it is possible to produce dose-ratios on ileum with 10 nM I which are about 100 times those on atria. After about 30 min exposure to solutions of I (prepared 15–20 min previously so that formation of aziridinium ions is well-established) the graph of log (dose-ratio) against time is linear and similar plots were obtained with two different agonists, carbachol and ethoxyethyltrimethylammonium. With results for the ileum, extrapolation of the line suggests that it does not start from zero (dose-ratio = 1): this is because of an initial relatively rapid reversible block. This early phase is similar to that seen on ileum with 10 nM 4DAMP methobromide, which is a competitive antagonist, so is probably caused by competitive block by the aziridinium ion, which closely resembles 4DAMP metho-salts. The subsequent irreversible phase should be caused by alkylation of the receptors. I is easy to make and should be a valuable tool for the study of muscarinic receptors.
Effect of Nipradilol on Myocardial Energy Metabolism in the Dog Ischaemic Heart
Authors: Hayase Nobumasa , Chiba Kaoru , Ichihara Kazuo , Inagaki Shun-Ichi , Abiko Yasushi 
Published: April 2011

Abstract
The effect of nipradilol, a newly developed β-adrenoceptor blocking agent with a vasodilatory action, on myocardial energy metabolism has been examined in the dog ischaemic heart, and compared with that of propranolol. Ischaemia was induced by ligating the left anterior descending coronary artery. Either saline, nipradilol (0.3 mg kg1), or propranolol (1 mg kg−1) was injected intravenously 5 min before coronary ligation. After 3 or 30 min of coronary ligation, the ischaemic region of the myocardium was removed, and the endocardial portion used to determine the levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), creatine phosphate (CrP) and lactate. Ischaemia decreased the levels of ATP and CrP, and increased the levels of ADP, AMP and lactate. Immediately after the injection of nipradilol, rapid falls in blood pressure and heart rate were observed. Pretreatment with nipradilol lessened the decreases in the levels of ATP and CrP and the increases in the levels of AMP and lactate, caused by 3 min of ischaemia, to the same extent as propranolol. However, after 30 min of ishchaemia, nipradilol had no effect on myocardial metabolism unlike propranolol. These results indicate that nipradilol can reduce ischaemic influences on myocardial metabolism as well as propranolol, but only in the early stages of ischaemia.
The sorption of isosorbide-5-mononitrate to intravenous delivery systems
Authors: De Muynck C , Colardyn F , Remon J P 
Published: April 2011

Abstract
The sorption of isosorbide-5-mononitrate, diluted in 0.9% NaCl or 10% glucose solutions, to intravenous delivery systems was investigated. Infusion bags, burettes, a syringe, infusion tubings and end-line filters were tested in static and in dynamic experiments. No clinically significant sorption was detected during those experiments. The use of PVC tubings of different hardness did not influence the results.
Role of unstirred water layer in the exsorption of quinidine
Authors: Huang Jin-Ding 
Published: April 2011

Abstract
Intestinal exsorption of salicylic acid, thiopentone, theophylline, and quinidine was measured during perfusion of the intestinal lumen with Tyrode solution. The effect of pectin or bovine serum albumin added to the perfusate on intestinal clearance (CL,) was investigated. Increasing pectin concentration from 00 to 0.5, 1.0 and 1.5% gave CL, values for quinidine of 499 ± 18, 363 ± 35, 237 ± 56, and 300 ± 28 mL h−1 kg−1, respectively. One per cent of pectin in the perfusate also decreased the CL, of thiopentone, but had no effect on the CLi of salicylic acid or theophylline. Pectin may have increased the thickness of the unstirred water layer on the mucous membrane and the resistance of drug exsorption for some drugs. When bovine serum albumin was added, drug binding in the perfusate increased, and the CLi of salicylic acid, thiopentone, and theophylline increased; the CLi of quinidine was unaltered. Co-administration of theophylline with quinidine decreased the CLi of quinidine without affecting quinidine binding in serum or in the perfusate. The CLi theophylline was not affected by quinidine. These observations are consistent with the hypothesis that the exsorption of quinidine is rate-limited by diffusion through the unstirred water layer on the mucous membrane. The CLi of quinidine is affected by the microclimate-pH in the unstirred water layer. An alternative possibility is that quinidine exsorption is mediated by a carrier-transport pathway.
Survey Variation in the THC Content of Illicitly Imported Cannabis Products—1984–1989
Authors: Pitts J E , O'Neil P J , Leggo K P 
Published: April 2011

Abstract
The tetrahydrocannabinol (THC) content of more than 180 samples of fresh illicit Cannabis products, seized by H.M. Customs and Excise on entry into Great Britain and Northern Ireland over the period 1984–1989, has been determined by gas chromatography. The average THC content of herbal cannabis remained high due to good quality cannabis from Jamaica and the USA, but that of cannabis resin was slightly lower. Resin from Morocco has changed significantly in its physical appearance. There was no fresh seizure of cannabis oil in this period.
Nanoparticle Uptake by the Rat Gastrointestinal Mucosa: Quantitation and Particle Size Dependency
Authors: Jani Praful , Halbert Gavin W , Langridge John , Florence Alexander T 
Published: April 2011

Abstract
Polystyrene microspheres in the size range 50 nm to 3 μm were fed by gavage to female Sprague Dawley rats daily for 10 days at a dose of 1.25 mg kg−1. Previous histological evidence of the uptake of these particles and their absorption across the gastrointestinal tract and passage via the mesentery lymph supply and lymph nodes to the liver and spleen was confirmed by analysis of tissues for the presence of polystyrene by gel permeation chromatography. Measurement of radioactivity of tissues following administration of 100 nm and 1 μm I125-labelled polystyrene latex particles for 8 days was corroborative although less secure because of the potential lability of the labelled particles. The extent of absorption of 50 nm particles under the conditions of these experiments was 34% and of the 100 nm particles 26% (as measured by determination of polystyrene content), of which total, about 7% (50 nm) and 4% (100 nm), was in the liver, spleen, blood and bone marrow. Particles larger than 100 nm did not reach the bone marrow, and those larger than 300 nm were absent from blood. No particles were detected in heart or lung tissue.
The measurement of internal pressure of ampoules and its application to commercial products
Authors: Tatsuhara Tohru , Tabuchi Fumie , Imai Yoko 
Published: April 2011

Abstract
This paper reports a method for determining the internal pressures of ampoules, from the head space and the change in volume on opening, as measured by displacement of water. Using this method, internal pressures of commercial ampoules were shown to be lower than atmospheric pressure. For example, the ratio of internal pressure to atmospheric pressure in a commercial ampoule of 5 mL distilled water was 0.884 at room temperature (23°C).
Effect of myrcene on nociception in mice
Authors: Rao V S N , Menezes A M S , Viana G S B 
Published: April 2011

Abstract
Myrcene, a monoterpene isolated from lemon grass oil (Cymbopogon citratus) has been investigated for antinociception in mice by a low temperature (51.5 ± 0.5°C) hot plate method and by the acetic acid-induced writhing test. Significant inhibition of nociception was seen in the tests with myrcene at doses of 10 and 20 mg kg−1 (i.p.) or at 20 and 40 mg kg−1 (s.c), respectively. The antinociceptive effect was significantly antagonized by naloxone (1 mg kg−1) or yohimbine (2 mg kg−1). The results suggest that myrcene is capable of inducing antinociception in mice, probably mediated by α2-adrenoceptor stimulated release of endogenous opioids.
Oxidative deamination of aliphatic amines by rat aorta semicarbazide-sensitive amine oxidase
Authors: Yu Peter H 
Published: April 2011

Abstract
Rat aorta semicarbazide-sensitive amine oxidase (SSAO) exhibits very high affinity in the deamination of an homologous series of aliphatic amines of 1 to 18 straight chain carbon atoms. The Km value decreases substantially as the chain length of these amines increases. The Vmax values are higher for the short chain amines. Diamines are poor substrates for SSAO or are not acted upon by the enzyme. The substrate preference for SSAO differs from that for monoamine oxidase.
The (+)-enantiomer is responsible for the antiplatelet and anti-inflammatory activity of (±)-indobufen
Authors: Cerletti Chiara , Manarini Stefano , Colombo Monica , Tavani Alessandra 
Published: April 2011

Abstract
The racemic compound indobufen and its (+)-and (—)-enantiomers have been compared for their effects on blood platelet function and rat carrageenan pleurisy. The antiplatelet properties were studied in-vitro in human platelets by measuring the inhibition of platelet aggregation and generation of serum thromboxane (Tx) B2. In-vivo, the antiplatelet and anti-inflammatory properties were studied in rats by measuring the inhibition of serum TxB2, the amount of 6-keto-PGF1α in pleural exudate and pleural exudate volume. In all tests the (+)-enantiomer was slightly more potent than the racemate, while the (—)-enantiomer was far less potent. In the same rats, treatment with the lowest doses of the compounds giving 90% inhibition of serum thromboxane B2 generation was associated with occasional macroscopic lesions of the gastric mucosa.
Comparison of Sensitization to Ambulation-increasing Effects of Cocaine and Methamphetamine after Repeated Administration in Mice
Authors: Hirabayashi Makizo , Okada Shizuka , Tadokoro Sakutaro 
Published: April 2011

Abstract
The effects of repeated (5 times) subcutaneous administration of cocaine (10, 20 or 40 mg kg−1) and methamphetamine (1, 2 or 4 mg kg−1) at 3–4 day intervals have been compared in mice placed individually into tilting activity cages. A progressive enhancement of the ambulation-increasing effect was noted for 3–4 h after each administration, indicating that sensitization occurred. This occurrence and the existence of an optimal dose producing sensitization were similar for both drugs. However, enhancement of the effect after cocaine progressed rapidly and maximum sensitization was observed earlier than after methamphetamine administration. Moreover, the higher doses of cocaine (40 mg kg−1) caused stereotypies concurrent with preconvulsive signs of short duration that were enhanced by serial administration. In contrast, methamphetamine caused a more progressive enhancement, but stereotypies with no preconvulsive signs were produced by the higher dose (4 mg kg−1). The respective, effective doses for the development of enhancement suggested that cocaine was less potent than methamphetamine in producing sensitization. Cross-sensitization occurred between both drugs. Thus, sensitization to cocaine was distinct from that to methamphetamine due to differences in its rapidity, intensity, and the presence or absence of preconvulsive changes.
Characterization of the Subtype of Presynaptic (α2-Adrenoceptors Modulating Noradrenaline Release in Cat and Bovine Cerebral Arteries
Authors: Arribas Silvia , Galvan Rosa , Ferrer Mercedes , Herguido Maria J , Marin Jesus , Balfagín Gloria 
Published: April 2011

Abstract
The possible existence of a heterogeneous population of α2-adrenoceptors (α2A and α2B, demonstrated by binding studies) in adrenergic nerve endings of cat and bovine cerebral arteries modulating noradrenaline release was investigated. Electrical field stimulation elicited an increase of tritium secretion from these vessels preincubated with (±)-[3H]noradrenaline, which was reduced by the α2-agonists, clonidine (1 μM) and B-HT 920 (0·01 and 0·1 μm), in cat cerebral arteries but only by B-HT 920 in bovine cerebral arteries. This reduction was inhibited by the antagonist of the α2B-subtype, prazosin, and the antagonists of α2A- and α2B-subtypes yohimbine and particularly rauwolscine. The effect of B-HT 920 was partially inhibited by clonidine in bovine, but not in cat cerebral arteries. In both types of arteries, prazosin, yohimbine and the α1-agonist methoxamine (all at 1 μm) failed to modify the stimulated radioactivity liberation, whereas it was increased by 1 μm rauwolscine, and by yohimbine plus prazosin in cat cerebral arteries. The basal tritium release was enhanced by rauwolscine and prazosin in cat cerebral arteries but only by the latter in bovine cerebral arteries. These results suggest: (1) the existence of presynaptic α2-adrenoceptors, mainly of the α2B-subtype, in these vessels negatively modulating noradrenaline release, their activity being greater in cat than in bovine cerebral arteries, and (2) clonidine has no agonistic but a weak antagonistic action in the latter vessels.
The blood binding of cefotiam and cyclohexanol, metabolites of the prodrug cefotiam hexetil, in-vitro
Authors: Querol-Ferrer V , Zini R , Tillement J-P 
Published: April 2011

Abstract
The binding of cefotiam and cyclohexanol to human serum, isolated proteins and erythrocytes has been studied in-vitro by equilibrium dialysis. The two molecules are 50% bound to serum proteins and the free fraction for both compounds remained constant within the therapeutic concentration range. Human serum albumin (HSA) was exclusively responsible for the cefotiam binding (48%) with a saturable process characterized by one binding site (n=1·00±0·14) with a very weak affinity (Ka=1457 ± 352 m−1). Like other cephalosporins, cefotiam showed no binding to α1-acid glycoprotein, lipoproteins or γ-globulins. Cyclohexanol is mainly bound to HSA with a weak affinity (Ka ∼ 1 800 m−1) but lipoproteins and α1-acid glycoprotein bind about 30% of bound cyclohexanol in serum. Interactions with free fatty acids (FFA) or bilirubin were studied at physiopathological concentrations. HSA-bound cefotiam was displaced by FFA (1260 μM) and bilirubin (330 μM), whereas the cyclohexanol binding was inhibited only by FFA. The cefotiam binding site seems to be close to the warfarin site (site I) whereas cyclohexanol probably shares the diazepam site (site II) on HSA. There is no mutual inhibition of binding between cefotiam and cyclohexanol at therapeutic levels. The binding of both compounds to erythrocytes is low and restricted when measured in the presence of plasma.
The negative inotropic effect of diazepam in rat right ventricular strips
Authors: Hernández Jesús 
Published: April 2011

Abstract
The effect of diazepam on cardiac contractility was investigated in electrically-driven right ventricular strips of the rat. Diazepam produced a concentration-dependent negative inotropic effect which was antagonized by either flumazenil, a benzodiazepine central-type receptor antagonist, or PK 11195, a benzodiazepine peripheral type receptor antagonist. The results suggest that the inhibitory effect of diazepam on cardiac contractility in the rat is mediated by both central and peripheral benzodiazepine receptors.
Investigations into the Pharmacodynamic Effects of Dermally Administered Microemulsions Containing β-Blockers
Authors: Kemken J , Ziegler A , Müller B W 
Published: April 2011

Abstract
Water uptake from the skin changes dermally applied near-saturated solutions of β-blockers in microemulsion-bases into supersaturated microemulsions. Due to an enhanced thermodynamic activity, high absorption rates are expected from these preparations. The pharmacodynamic effect after dermal administration of such preparations has been evaluated using rabbits as a suitable in-vivo model. The dose dependency, influence of lipophilicity and of the thermodynamic activity of the drug is described. Assessment of dermal doses which were therapeutically equivalent to i.v. doses as, for example, shown with carazolol is possible. Although not all observed pharmacodynamic effects were due to these influences but rather due to the numerous other skin-vehicle-drug interactions which could not be explained with this model, the presented in-vivo model is helpful in evaluation of β-blockers which were suitable candidates for transdermal administration.
The role of the gastric mucosal sulphydryls in the ulcer-protecting effects of sulphasalazine
Authors: Garg G P , Cho C H , Ogle C W 
Published: April 2011

Abstract
The role of gastric mucosal sulphydryls in gastric ulceration, produced by restraint at 4°C (stress) for 2 h, and in the ulcer-protecting effects of sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), have been studied in rats. Stress significantly raised the mucosal sulphydryl content, but sulphasalazine and sulphapyridine did not influence these changes; only 5-aminosalicylic acid decreased the mucosal sulphydryl concentration. These results indicate that depletion of mucosal sulphydryls does not occur in stress-induced ulceration, in contrast to what has been shown in other experimental ulcer models. The antiulcer effects of sulphasalazine or of any of its constituents may, therefore, not involve the sulphydryl mechanism.
Decrease of Gastrointestinal Mucosal Damage by Salicyluric Acid Compared with Salicylic Acid in Rabbits
Authors: Nakamura Junzo , Katayama Michihiro , Kido Mitsuhiko , Nishida Koyo , Sasaki Hitoshi 
Published: April 2011

Abstract
The gastrointestinal mucosal damage following the oral administration of salicylic acid or salicyluric acid was examined in rabbits using a scanning electron microscope. Six and 24 h after treatment with salicylic acid, morphological changes of gastric mucosa were recognized. In rabbits treated with salicyluric acid, however, severe damage in the gastric mucosa was not found after 24 h compared with the treatment with salicylic acid. Following the treatment with salicylic acid, some mucosal damage in the duodenum, jejunum and ileum was observed after 24 h. The surface character of the duodenal, jejunal, ileal, caecal and colonic mucosa were almost identical compared with the control following the treatment with salicyluric acid. It was reported that salicyluric acid is metabolized to salicylic acid by the intestinal microorganisms. From these results, it was suggested that prodrugs utilizing the metabolism of salicyluric acid to salicylic acid by intestinal microorganisms may be useful in reducing gastrointestinal mucosal damage.
Lysophosphatidic Acids Induce Contraction of Rat Isolated Colon by Two Different Mechanisms
Authors: Tokumura Akira , Yube Nobuyuki , Fujimoto Hiroaki , Tsukatani Hiroaki 
Published: April 2011

Abstract
Lysophosphatidic acids (1-linoleoyl-, 1-linolenoyl, 1-arachidonoyl- and 1-O-hexadecyl-sn-glycero-3-phosphate) induced rapid contraction of rat isolated colon which was dependent on external Ca2+, 1-linolenoyl-lysophosphatidic acid having the greatest effect. The contraction induced by 1-linolenoyl-lysophosphatidic acid was reduced considerably by nifedipine and verapamil, but not by atropine or indomethacin. Phosphatidic acids with two short-chain acyl groups induced a small, atropine-sensitive contraction at 100 μM, but phosphatidic acids with two long-chain acyl groups were inactive. These results suggest that unlike phosphatidic acids, lysophosphatidic acids act directly on extracellular sites of the plasma membrane of smooth muscle cells in rat colon, mainly through activation of voltage-sensitive Ca2+ channels.