bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apparent down-regulation of rat brain μ and κ-opioid binding sites labelled with [3H]cycloFOXY following chronic administration of the potent 5-hydroxytryptamine reuptake blocker, clomipramine
Authors: Benkelfat Chawki , Aulakh Charanjit S , Bykov Victor , Rice Kenner C , de Costa Brian R , Rothman Richard B 
Published: April 2011

Abstract
This study examined the effect of chronic clomipramine administration on opioid μ- and κ-binding sites. Clomipramine (5 mg kg−1 day−1) or saline was administered to rats via osmotic minipumps for 3 days or 28 days. Lysed-P2 brain membranes were prepared and preincubated for 60 min without (control membranes) or with 1 μM of the μ-selective acylating agent, 2-(4-ethoxybenzyl)-1-diethylaminoethyl-5-isothiocyanato-benzimidazole-HCl (BIT), to deplete membranes of μ-binding sites. [3H]6-Desoxy-6β-fluoronaltrexone ([3H]cycloFOXY) was used to label μ and κ-binding sites. Weighted nonlinear least squares analysis of cycloFOXY binding surfaces permitted determination of the Kd and Bmax values of μ- and κ-binding sites in control and treated rats. Subacute (3 days) administration of rats with clomipramine had no significant effect on [3H]cycloFOXY binding. Chronic (28 days) administration of clomipramine produced a small (approximately 10%) but statistically significant decrease in the Bmax. These findings are discussed in reference to other studies that have examined the effect of chronic antidepressant administration on opioid receptors, and speculate that the endogenous opioid systems may play a role in obsessive-compulsive disorder.
Sustained release of buserelin acetate, a luteinizing hormone-releasing hormone agonist, from an injectable oily preparation utilizing ethylated β-cyclodextrin
Authors: Uekama Kaneto , Arima Hidetoshi , Irie Tetsumi , Matsubara Kazutaka , Kuriki Takeo 
Published: April 2011

Abstract
The possible use of heptakis (2,6-di-O-ethyl)-β-cyclodextrin (DE-β-CyD) as a parenteral sustained-release carrier for buserelin acetate, a luteinizing hormone-releasing hormone superagonist, has been examined. The in-vitro release of buserelin from the oily suspension was significantly retarded by the complexation with DE-β-CyD, mainly due to the poor water solubility of the complex. A single subcutaneous injection of the suspension containing the buserelin-DE-β-CyD complex to rats provided an effective continuous plasma level of buserelin lasting for at least one month, indicating a potential therapeutic efficacy for the treatment of the endocrine-dependent diseases. These results suggest that DE-β-CyD serves as an injectable sustained-release drug carrier suitable for chronic treatment with buserelin acetate.
An Infrared Study of Tautomerism in Acetohexamide Polymorphs
Authors: Girgis Takla Pamela , Dakas Christos J 
Published: April 2011

Abstract
Infrared data determined for known polymorphic forms and some new derivatives of acetohexamide and related compounds support the view that acetohexamide polymorphs exhibit keto-enol tautomerism. They indicate that type A polymorphs exist in the enol form, probably stabilized by intramolecular bonding between an O—H and S=O group to form a six-membered ring. Type B polymorphs exist in the keto form with the urea carbonyl group intermolecularly bonded to a sulphonamide N—H. The new evidence disputes previous interpretations of the data.
Evidence for a Postsynaptic Action of Neostigmine on Muscarinic Receptors in the Anococcygeus Muscle of the Rat
Authors: Smith J A , Spriggs T L B 
Published: April 2011

Abstract
In the rat anococcygeus muscle neostigmine induces atropine-sensitive, significant leftward displacements of the log concentration-response curves to both noradrenaline and 5-hydroxytryptamine. Responses to high K+ were also potentiated by neostigmine. However, high K+ elicited only small and irregular overflows of tritium from [3H]noradrenaline pre-incubated tissues, in contrast to the large overflow elicited by field stimulation. In addition guanethidine blocked responses to field stimulation but not those to high K+. This is consistent with the dose-related tension responses to high K+ being elicited postsynaptically. These results indicate that postsynaptic muscarinic receptors are involved in the potentiation by neostigmine of rat anococcygeus muscle responses to field stimulation or exogenous agonists, possibly by an action on receptor operated ion channels. Additional support for a postsynaptic site of action comes from the failure of neostigmine to potentiate tension responses to nerve or field stimulation in the chick expansor secundariorum, a muscle which is devoid of postsynaptic muscarinic receptors.
Relaxant Actions of Khellin on Vascular Smooth Muscle
Authors: Ubeda Amalia , Villar Angel 
Published: April 2011

Abstract
To clarify the mechanism of the vasodilatory action of khellin on calcium, we have investigated its relaxant action on base line and on K+ and noradrenaline-induced contractile tensions in rat aorta smooth muscle and on spontaneous contractile activity of rat portal vein. Khellin relaxed both of these preparations with a similar potency, which suggests a non-specific inhibition of calcium flux, without any difference related to the specific calcium channels. We have also studied the capacity of khellin to interfere with the loading and release mechanisms of caffeine and noradrenaline-sensitive calcium stores in Ca-free medium. Khellin’s Ca2+ loading reduction may be related with its capacity to inhibit calcium influx. Khellin applied during Ca2+ release also caused relaxation. We propose that this drug may enhance calcium extrusion or sequestration rather than the calcium release mechanism. These actions on calcium influx and intracellular mobilization can contribute to its vasorelaxant action.
Effects of opioid agonists on urine production in neonatal rats
Authors: Jackson Helen C , Kitchen I 
Published: April 2011

Abstract
The modulatory effects of opioids on urine production in adult rats have been well-documented. We report here the first investigation of the effects of these agents on urination in neonatal rats. The κ-agonists U50,488H (1, 10 mg kg−1) and (+)-tifluadom (10 mg kg−1) produced an increase in urine output in 10-day old pups whereas the (-)-isomer of tifluadom was ineffective in this model. The diuretic effects of the highest dose of U50,488H were attenuated by a 10 but not a 1 mg kg-1 dose of the opioid antagonist naltrexone. These findings suggest that κ-agonists, as in adult animals, produce diuresis in neonates by activity at κ-opioid receptors and also confirm the stereoselective nature of the response. The increase in urination produced by U50,488H (10 mg kg−1) was also reduced by the α-adrenoceptor antagonist phentolamine (1 mg kg−1), an observation which supports the hypothesis that κ-agonists—in addition to their well-established inhibitory effects on the release of antidiuretic hormone—may increase urination via an adrenergic mechanism at the level of the adrenal medulla. The μ-opioid agonist morphine (0·1–10 mg kg−1), in contrast to its observed effects in older animals, did not produce antidiuresis in either normally-hydrated or water-loaded 10-day old rat pups. The results of this study therefore show that the stimulatory effects of κ-agonists on urine production appear to be fully-functional at 10-days but the inhibitory effects of opioids on urination lag behind in development.
Employment of magnet-susceptible microparticles for the targeting of drugs
Authors: Kharkevich D A , Alyautdin R N , Filippov V I 
Published: April 2011

Abstract
It has been demonstrated in cats that magnet-susceptible microspheres and liposomes containing neuromuscular blocking agents (dipyronium, pyrocurinum and diadonium) caused a deeper inhibition of the neuromuscular transmission in the limb placed in the magnetic field than in the control limb located beyond the field. The microparticles containing a short-acting neuromuscular blocking agent diadonium appeared to have the highest selectivity of action. The present method allows a pronounced neuromuscular block in a target area to be achieved without noticeable effect on PCO 2 of the exhaled air.
The Material Tensile Strength of Convex-faced Aspirin Tablets
Authors: Pitt K G , Newton J M , Richardson R , Stanley P 
Published: April 2011

Abstract
The material tensile strength of a range of convex-faced tablets, compacted under controlled conditions at pressures of 40 and 320 MPa from a size fraction of acetylsalicylic acid, has been assessed. The calculation of the tensile strength σt, from observed fracture loads obtained in diametral compression testing, is based on the equation derived by Pitt et al (1988), namely:
where P is the fracture load, D is the tablet diameter, t is the overall tablet thickness and W is the central cylinder thickness. The strength of a tablet of a given shape compacted at 320 MPa was between two and four times greater than that of a similar tablet compacted at 40 MPa. For the thicker tablets (W/D ≥0·2) the material tensile strength was practically independent of shape. For the thinner tablets (W/D = 0·1) the material tensile strength varied considerably with face-curvature, showing a maximum for each of the two compaction pressures at a D/R value of 0·67.
Effect of β-Casomorphins on Intestinal Propulsion in the Guinea-pig Colon
Authors: De Ponti Fabrizio , Marcoli Manuela , Lecchini Sergio , Manzo Luigi , Frigo Gian Mario , Crema Antonio 
Published: April 2011

Abstract
β-Casomorphins are a family of opioid peptides originally isolated from β-casein. In view of a possible physiological significance of these milk-derived compounds, the effects of bovine β-casomorphin-5 (β-CM-5), β-casomorphin-4 (β-CM-4) and D-Ala2-β-casomorphin-4-NH2 (D-Ala2-β-CM-4-NH2) have been investigated on the peristaltic reflex in the guinea-pig isolated colon and compared with morphine. β-CM-5 and D-Ala2-β-CM-4-NH2 each dose-dependently inhibited the velocity of propulsion of an intraluminal bolus; β-CM-4 was ineffective. IC50 values were 0·30, 5·21 and 0·29 μfor morphine, β-CM-5 and D-Ala2-β-CM-4-NH2, respectively. The potency ratios vs morphine were 0·06 and 0·96 for β-CM-5 and D-Ala2-β-CM-4-NH2, respectively. Blockade of the peristaltic reflex by β-CM-5 or D-Ala2-β-CM-4-NH2 was reversed by the opioid antagonist naloxone. D-Ala2-β-CM-4-NH2 also dose-dependently inhibited resting acetylcholine output (IC50 = 5·69 μM; potency ratio vs morphine: 0·63). In conclusion, certain β-casomorphins inhibit intestinal propulsion and cholinergic neurotransmission in the guinea-pig colon, probably by acting at opioid receptors.
The Effect of Diazepam on Ventricular Automaticity Induced by a Local Injury. Evidence of Involvement of “Peripheral Type” Benzodiazepine Receptors
Authors: Ruiz F , Hernández J , Pérez D 
Published: April 2011

Abstract
The effect of diazepam on ectopic cardiac automaticity has been examined in rats. We also investigated whether “central” or “peripheral type” benzodiazepine receptors are involved, as well as the role of calcium, on the possible effect of diazepam, by studying the interaction of this drug with either GABA, Picrotoxin, RO 15–1788, PK 11195, diltiazem or Bay K 8644. A local injury of the rat isolated right ventricle produced a sustained abnormal rhythm which was completely abolished by diazepam (30–50 μu). This effect was not modified by the presence of either GABA (100 μM) Picrotoxin (2 μM) or RO 15–1788 (5 μM.) but it was reduced by the antagonist of “peripheral type” benzodiazepine receptors PK 11195 (0·1 μu). On the other hand the calcium channel blocker diltiazem (5 μM) and the calcium channel activator Bay K 8644 (3 nM), respectively, potentiated and reduced the effect of diazepam. It is concluded that diazepam effectively reduces ectopic cardiac automaticity in the rat. The “central type” benzodiazepine receptors are not involved in this effect, but it seems to be, at least, partially mediated by “peripheral type” receptors and is a calcium-dependent phenomenon.
Effects of Trimebutine Maleate on Electrical Activities of Isolated Mammalian Cardiac Preparations
Authors: Igawa Osamu , Kotake Hiroshi , Hirai Shozo , Hisatome Ichiro , Hasegawa Junichi , Mashiba Hiroto 
Published: April 2011

Abstract
The effects of trimebutine maleate on electrical activity in guinea-pig isolated papillary muscles and rabbit sino-atrial nodes have been studied by means of a standard microelectrode method. In papillary muscles, trimebutine (above 10 μM) decreased the maximum rate of rise (V̇max) and the action potential duration at 90% repolarization (APD90), whereas the resting potential was not significantly altered. As to a decrease in V̇max, trimebutine produced a negative shift of the curve relating V̇max to the resting potential along the voltage axis. Trimebutine also depressed the slow action potentials of papillary muscles produced by 27 mM K and 0·2 mitt Ba. In spontaneously beating sino-atrial node preparations, trimebutine (above 10 μ) decreased the heart rate, V̇max and the rate of diastolic depolarization. These results indicate that trimebutine maleate possesses a depressant action on the electrical activities of the fast- and slow-response fibres of the heart mainly due to inhibitions of both fast Na+ and slow Ca2+ channels.
Continuous shear rheometry of o/w emulsions; control of evaporation in cone/plate geometry
Authors: Orafidiya Lara O 
Published: April 2011

Abstract
Volatile solvents may evaporate during cone/plate viscometry so that false rheograms develop. This surface evaporation was prevented in a cod-liver oil-in-water emulsion stabilized with zanthoxylum gum by layering a film of cod-liver oil on the exposed surface of the emulsion test sample. The oil layer effectively prevented evaporation and did not alter significantly the rheological behaviour of the test material.
The effects of dipyridamole and indomethacin on methotrexate cytotoxicity in LoVo human colon cancer cells
Authors: Gaffen J D , Chambers E A , Bennett A 
Published: April 2011

Abstract
Dipyridamole and indomethacin were studied for their effects in the in-vitro response of LoVo colon cancer cells to methotrexate (MTX) using a dye elution method. Dipyridamole 0·5–5 μg mL−1 or indomethacin 1 μg mL−1 alone had little or no effect on cell growth. The tumour cells were refractory to even high concentrations of MTX (2·5–10 μg mL−1) alone or with indomethacin 1 μg mL−1. In contrast, dipyridamole 0·5–5 μg mL−1 sensitized the cells to MTX 5 μg mL−1 (their growth was reduced by 25 to 69%), possibly by inhibiting thymidine salvage.
2-[125I]Iodomelatonin binding sites in hamster and chick exhibit differential sensitivity to prazosin
Authors: Pickering D S , Niles L P 
Published: April 2011

Abstract
Binding of 2-[125I]Iodomelatonin to putative receptors for melatonin has been well documented in chicken and hamster tissues. Differences in the potency of N-acetyl-5-hydroxytryptamine in these tissues suggested distinct central and peripheral binding sites. Prazosin was found to be much more potent (Ki = 6–5 nm) in hamster hypothalamus than in chick retina (Ki = 740 nm). N-acetyl-5-HT also was more potent in hamster hypothalamus (Ki = 14 nm) than in chick retina (Ki = 1050 nm). A comparison of hamster hypothalamus to chick forebrain revealed a similar difference in potency for prazosin. In light of these findings, the dissimilarity between the potencies of N-acetyl-5-HT and prazosin in hamster and chick would appear to be due to a species difference as the central and peripheral sites seem alike within either species.
A study of β-adrenoceptors in rat lung parenchymal strip
Authors: Candenas Maria L , Anselmi Elsa 
Published: April 2011

Abstract
The aim of the present study was to characterize the β-adrenoceptor population in rat lung strip. For this purpose, Schild plots were obtained for the β-adrenoceptor antagonists atenolol (β1-selective), butoxamine (β2-selective) and propranolol (nonselective), using three different agonists: isoprenaline (non-selective), salbutamol (β2-selective) and noradrenaline (β11-selective). The slopes of these Schild plots were close to the theoretical value of unity, and pA2 values determined with isoprenaline, salbutamol and noradrenaline as agonists were: for propranolol, 7·86 ± 0·22, 7·72 ± 0·15 and 7·89 ± 0·23; for atenolol, 5·19 ± 0·05, 5·33 ± 0·07 and 5·47 ± 0·22 and for butoxamine, 6·31 ± 0·11, 6·34 ± 0·03 and 5·99 ± 0·23, respectively. These data suggest that pharmacological responses of rat isolated lung strip to β-adrenoceptor agents are mediated by a homogeneous population of β2-adrenoceptors, although the presence of a minor population of β1-adrenoceptors undetected by the agonists used cannot be excluded.
Interaction of Nefopam and Orphenadrine with the Cytochrome P-450 and the Glutathione System in Rat Liver
Authors: Leurs R , Donnell D , Timmerman H , Bast A 
Published: April 2011

Abstract
Nefopam, a cyclic analogue of orphenadrine, exhibits a type I (substrate) and a type II (ligand) interaction with ferri-cytochrome P-450 in control and phenobarbitone induced rat hepatic microsomes respectively. In-vitro metabolism of nefopam in phenobarbitone-induced microsomes leads to the production of a reactive metabolite which complexes with cytochrome P-450. In contrast to the known complexation of orphenadrine, complexation by nefopam can be inhibited by glutathione (GSH, 0·1-1·0 mm). However, in-vivo administration of nefopam to rats does not diminish the GSH content of liver cytosol nor increase oxidized glutathione levels nor alter the activities of GSH transferase and GSH peroxidase. In-vivo administration does not lead to cytochrome P-450 induction nor cytochrome P-450 complexation as has been shown for orphenadrine. Finally, nefopam inhibits the NADPH dependent endogenous H2O2 production in both control and phenobarbitone-induced microsomes.
Specific Age-dependence in Capacity-limited Uptake of Propranolol by Isolated Rat Lung
Authors: Iwamoto Kikuo , Watanabe Jun , Yonekawa Hina 
Published: April 2011

Abstract
To investigate the effect of age on the pulmonary uptake of propranolol, minced tissue (0·4 g) of lungs isolated from 3- to 104-week-old rats was incubated with the drug (1 to 500 ng μL−1) prepared in oxygenated, pH 7·4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BS A for 60 min at 37°C. In any age-group the metabolism of propranolol was not significant (i.e. less than 0·6% of any initial load) under the present in-vitro conditions. The extent of uptake after the incubation with 2·5 μ mL−1 of the drug was largest in the 7 weeks (i.e. 82% of the initial load) and relatively small in the 3(64%), 24(61 %), 52(51%) and 104(48%) week old rats. Similar, specific age-dependence was observed in the tissue-to-medium concentration ratio of the drug. In any age-group, the initial uptake rate obtained in the first 5 min of the incubation was found to be a combination of apparently linear transport and saturable (capacity-limited) processes. There was a marked, specific age-dependence in the capacity-limited uptake rate. Although Km′ value was almost equivalent in any age-group (i.e. 24·4 to 25·4 μg mL1), Vmax exhibited a specific age-dependence by yielding the highest value in 7 weeks (0·726 ± 0·101 mg g−1 min−1) and relatively low values in 3 (0·501 ±0·082 mg g−1 min−1), 52 (0·410 ± 0·088 mg−1 g−1 min1) and 104 (0·397 ± 0·074 mg g−1 min−1) weeks.
Pharmacokinetics of 8-phenyltheophylline in the rat
Authors: Wormald A , Bowmer C J , Yates M S , Collis M G 
Published: April 2011

Abstract
The pharmacokinetics of the adenosine antagonist 8-phenyltheophylline (8-PT) have been investigated in the rat. After intravenous administration to male rats with normal renal function, 8-PT was rapidly cleared from plasma with a t 1/2 of about 14 min. Its apparent volume of distribution was some 76 mL/100 g and plasma clearance was 3·5 mL min−1 g. Injection via the carotid artery did not alter the kinetics of 8-PT, but when given through the porta) vein a first-pass effect was observed. Moreover, 8-PT could not be detected in plasma following intraperitoneal injection. The kinetics of 8-PT were not altered in male rats with acute renal failure and no difference was noted between male and female animals with respect to the kinetics of 8-PT following intravenous injection. It is concluded that the pharmacokinetic properties of 8-PT are likely to complicate its use in-vivo.
Rapid production of ulcerative disease of the colon in newly-weaned guinea-pigs by degraded carrageenan
Authors: Marcus A J , Marcus S N , Marcus R , Watt J 
Published: April 2011

Abstract
In a dose-response study, degraded carrageenan (Eucheuma spinosum) was supplied in the drinking fluid at 1,2 and 3% concentrations over two weeks to young adult guinea-pigs. Ulceration of the large bowel was produced in 100% of animals, the severity and extent of damage probably being dose-related. In a time-course study, 3% degraded carrageenan solution supplied to newly-weaned guinea-pigs produced in 100% of animals ulceration in the caecum by four days and in the ascending colon by seven days. The onset of ulceration occurred as early as the second day. This model is convenient and economic for the screening of drugs of potential therapeutic value in human ulcerative colitis.
Inhibition of Dapsone-induced Methaemoglobinaemia by Cimetidine in the Presence of Trimethoprim in the Rat
Authors: Coleman M D , Russell R M , Tingle M D , Park B K 
Published: April 2011

Abstract
Administration of dapsone in combination with trimethoprim and cimetidine to male rats resulted in a marked decrease (P &lt; 0·05) in measured methaemoglobin levels (46·2±24% Met Hb h) compared with administration of dapsone alone (124·5 ± 24·4% Met Hb h). The elimination half-life of dapsone (814 ± 351 min) was more than doubled in the presence of trimethoprim and cimetidine compared with control (355 ± 160 min, P &lt; 0·05). However, there were no significant differences in AUC and clearance when dapsone was administered in combination with trimethoprim and cimetidine compared with dapsone alone. Co-administration of trimethoprim with dapsone in the absence of cimetidine did not affect either methaemoglobin formation, AUCs, half-lives, or clearance values of dapsone compared with control. There was a threefold increase in the AUC of trimethoprim (6296 ± 2249 μg min mL−1) in the presence of dapsone compared with trimethoprim alone (2122 ± 552 μg min mL−1). There was also a corresponding decrease in the clearance of trimethoprim in the presence of dapsone compared with control (19·1±6·9 vs 60·8 ± 21·0 mL min−1). However, there was no change in the elimination half-life of trimethoprim between the two experimental groups (273 ± 120 vs 292 ± 54 min). The AUC of trimethoprim increased more than threefold in the presence of cimetidine (7100 ± 1501 μg min mL−1) compared with trimethoprim alone (2122 ± 552 μg min mL−1). There was also a corresponding reduction in the clearance of trimethoprim in the presence of cimetidine (61·2 ± 21·2 vs 17·8 ± 9·3 mL min−1) compared with control. However, there was no significant change in the elimination half-life of trimethoprim after the administration of cimetidine (273 ± 136 vs 215 ± 109 min). Administration of either trimethoprim or cimetidine alone did not cause methaemoglobin levels to exceed control values. The administration of trimethoprim with dapsone and cimetidine resulted in a significant increase in AUC (2122 ± 552 vs 5744 ± 3289 μg min mL−1), a fall in clearance (17·8 ± 9·3 vs 60·8 ± 21 mL min−1), but no change in half-life (252 ± 134 vs 273 ± 136 h) of trimethoprim. The co-administration of cimetidine significantly reduced dapsone-mediated methaemoglobin formation in the presence of trimethoprim, whilst the AUC of trimethoprim was significantly increased in the presence of both cimetidine and dapsone.