bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of acute reserpine administration on the sensitivity of the isolated pacemaker from rat heart to isoprenaline and noradrenaline
Authors: Spadari Regina C , Lamas José Luiz T , De Moraes Sergio 
Published: April 2011

Abstract
The effects of reserpine on the sensitivity of the isolated pacemaker from rat heart to the chronotropic effect of isoprenaline and noradrenaline were studied. A single large dose of reserpine (2&#x006d;̇5 mg kg−1) administered to rats 24 h before killing induces supersensitivity of the isolated pacemaker to isoprenaline, leaving unaltered the responsiveness of the pacemaker to noradrenaline. Reserpine at the dose of 1&#x006d;̇0 mg kg−1 did not alter the sensitivity of the pacemaker to the catecholamines. Only the larger dose of reserpine raised the corticosterone plasma level. It is possible that a corticosterone-mediated inhibition of the extraneuronal uptake process is responsible for the supersensitivity to isoprenaline. Large doses of reserpine should not be used in experiments aimed to study cardiac sensitivity to isoprenaline or extraneuronal uptake and metabolism of the catecholamine.
Identification of two metabolites of the cholinesterase reactivator HI-6 isolated from rat urine
Authors: Ligtenstein David A , Wils Eric R J , Kossen Simon P , Hulst Albert G 
Published: April 2011

Abstract
Two metabolites, isolated from the urine of rats given the cholinesterase reactivator HI-6 intravenously, still contained quaternary nitrogen atoms and therefore could not be extracted from aqueous solutions by organic solvents. Both metabolites were isolated by preparative high performance liquid chromatography and were identified using mass spectrometry, gas chromatography, infrared spectrometry, ultraviolet spectrometry and proton nuclear magnetic resonance spectrometry. The structures were confirmed by in-vitro preparation of the compounds. Both metabolites contained 2-pyridone moieties. One had an intact pyridinium-aldoxime moiety, and therefore could still be therapeutically active. The excretion of unchanged HI-6 together with the two identified metabolites does not provide for a 100% mass balance, indicating that in the rat, other, as yet unidentified, metabolites must be formed.
Central dopamine receptors and their role in digoxin-induced cardiotoxicity in the dog
Authors: Plunkett L M , Tackett R L 
Published: April 2011

Abstract
The role of the dopaminergic system in digoxin-induced cardiotoxicity has been examined. Specific dopaminergic agonists and antagonists were administered into the ventriculo-cisternal system of pentobarbitone-anaesthetized dogs before systemic administration of digoxin. Pretreatment with apomorphine, a specific dopamine agonist, did not significantly alter the arrhythmogenic or lethal doses of digoxin. However, the digoxin-induced increase in CSF noradrenaline was decreased significantly in apomorphine-pretreated animals. Pretreatment with pimozide, a specific dopamine antagonist, significantly decreased the arrhythmogenic dose of digoxin but did not alter the lethal dose. As with apomorphine, pimozide-pretreated animals accumulated significantly less noradrenaline in CSF compared with control dogs. These results suggest that dopamine receptors are not directly related to the cardiotoxic actions of digoxin. However, dopaminergic receptors may influence the balance of central catecholaminergic systems that influence the peripheral cardiovascular system.
Experimental pharmacological study of moroxybrate, a hypolipidaemic, antithrombotic, antiatheromatous agent
Authors: Moreau Pierre , Jacotot Bernard , Tillement Jean-Paul 
Published: April 2011

Abstract
Moroxybrate, a drug obtained by the reaction of clofibric acid with moroxydine, a biguanide with practically no effect on carbohydrate metabolism, has been examined for its effects on blood lipids, fibrinogen, in-vitro platelet aggregation, and also on experimental atherosclerotic lesions obtained by feeding the rabbits a diet containing 1% cholesterol. At the same dose, moroxybrate has an effect at least equal to those of clofibrate and moroxydine alone, on the lipidic parameters and haemostasis in rat and rabbit. The combination of these actions together with an effect on the prevention of experimental atherosclerosis lesions in the rabbit suggests moroxybrate should be examined for its effects in ischaemic cardiovascular disease.
The effect of polycarbophil on the gastric emptying of pellets
Authors: Khosla R , Davis S S 
Published: April 2011

Abstract
The influence of the putative bioadhesive, polycarbophil, on the gastric emptying of a pellet formulation, has been investigated in three fasted subjects. The pellets were radiolabelled with technetium-99m. Gastric emptying was measured using the technique of gamma scintigraphy. The pellets emptied from the stomach rapidly and in an exponential manner. Polycarbophil did not retard the gastric emptying of the pellets.
The Accumulation Mechanism of Cationic Mitomycin C-dextran Conjugates in the Liver: In-vivo Cellular Localization and In-vitro Interaction with Hepatocytes
Authors: Nakane Sachi , Matsumoto Satoshi , Takakura Yoshinobu , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
To elucidate the mechanism of the accumulation of mitomycin C-dextran conjugate (MMC-D) in the liver, in-vivo cellular uptake and in-vitro cellular interaction of MMC-D have been studied. Localization of cationic and anionic MMC-D (MMC-Dcat. and MMC-Dan.) in different liver cell types following i.v. administration was examined in rats and the significant contribution of parenchymal cells demonstrated. In-vitro cellular interaction was determined by measuring the drug concentration in the medium after incubation with rat isolated hepatocytes. MMC-Dcat. was highly adsorbed on the surface of hepatocytes at pH 7.2, while the interaction between MMC-Dan. and hepatocytes was negligible. The percentage association of MMC-Dcat. with hepatocytes remained almost constant during the course of incubation and no significant difference was observed between the incubation at 4 and 37 °C. The adsorption phenomenon was shown to conform to Langmuir’s adsorption isotherm. The amount of MMC-Dcat. associated with hepatocytes increased as the molecular weight of the dextran chain increased. These results showed that MMC-Dcat. was adsorbed on the surface of hepatocytes by an electrostatic force and this binding was responsible for its remarkable accumulation in the liver in-vivo. Thus some physicochemical properties of the MMC-D conjugates are thought to play an important role in the disposition characteristics of the conjugates.
Formation and Release of [3H] Acetylcholine in the Rat Urinary Bladder Strip
Authors: D'Agostino G , Chiari M C , Grana E 
Published: April 2011

Abstract
The relationship between different frequencies of loading stimulation and [3H]acetylcholine (ACh) formation and release from nerve terminals has been investigated in extratrigonal strips of the urinary bladder of the rat. An increase in frequency (0.2, 0.4 and 0.8 Hz) for the 30 min incubations with [3H]choline produced an enhancement of storage of [3H]ACh from 19.5 to 34% of total tritium content in the tissue. Higher frequencies (1.6 and 3.2 Hz) failed to increase storage further on. The [3H]choline content did not vary significantly. Electrical field stimulation at 2 Hz (360 shocks) produced a release of tritium. The evoked outflow was higher when the strip was loaded at 0.8 Hz than at the other frequencies tested. Both [3H]ACh and [3H]choline were measured in the perfusate of strips preloaded at 0.8 Hz. Most of the induced outflow was found to be [3H]ACh, as in previous experiments carried out using 0.2 Hz as a loading frequency. The findings suggest that in the rat urinary bladder strip loading at 0.8 Hz is suitable for increasing the formation and the resulting release of [3H]ACh during electrical stimulation.
Interaction of the Anticonvulsants, Denzimol and Nafimidone, with Liver Cytochrome P450 in the Rat
Authors: Salmona M , Conti I , Testa R , Fracasso C , Caccia S 
Published: April 2011

Abstract
The presence of an imidazole moiety in the chemical structure of denzimol and nafimidone suggested that these new anticonvulsants might interfere with cytochrome P450-mediated mixed function monooxygenase activities. We therefore investigated their ability to bind reversibly to rat liver cytochrome P450. Both drugs displayed a type II spectra. The Ks values of binding were 6.66 and 7.00 mM, respectively, for denzimol and nafimidone. In other in-vitro studies the IC50 of the inhibition caused by denzimol and nafimidone was determined on carbamazepine (CBZ) epoxidation and diazepam C3-hydroxylation and N1-dealkylation. The IC50 values for CBZ epoxidation were 4.46 × 10−7 and 2.95 × 10−7 M, respectively, in the presence of denzimol and nafimidone. The IC50 values for diazepam C3-hydroxylation were 1.44 × 10−6 and 1.00 × 10−6 M, respectively, and those for N1-dealkylation 6.66 × 10−7 and 5.95 × 10−7 M. The inhibition of CBZ metabolism was also investigated ex-vivo and in-vivo after single oral doses (15 and/or 60 mg kg−1) of denzimol or nafimidone. Inhibition of CBZ-10,11-epoxidation by the two drugs was time- and dose-dependent. Further studies in-vivo showed that denzimol and nafimidone prolong pentobarbitone sleeping times indicating that both drugs bind to rat liver microsomes and are potent inhibitors in the rat of mixed function monooxygense activities both in-vitro and in-vivo.
Retention of Soman in Rats, Guinea-pigs and Marmosets: Species-dependent Effects of the Soman Simulator, Pinacolyl Dimethylphosphinate (PDP)
Authors: van Helden H P M , van der Wiel H J , Wolthuis O L 
Published: April 2011

Abstract
Whether the temporary retention of intact soman in the rat and its subsequent delivery from tissues into the circulation of the blood is also demonstrable in guinea-pigs and marmosets has been investigated as was whether the soman simulator PDP (pinacolyl dimethylphosphinate) prevented this retention. Electric eel AChE, intravenously injected 1.5 h after an intravenous soman intoxication into anaesthetized, atropinized and artificially ventilated guinea-pigs (150 μg kg−1 soman), marmoset monkeys (100 μg kg−1 soman) and rats (330 and 172.5 μg kg−1 soman) lost its activity faster than enzyme injected in non-intoxicated animals. Electric eel AChE incubated in the presence of pectoralis or diaphragm muscle isolated from soman-intoxicated rats, guinea-pigs and marmosets 0.5 or 1.5 h after the intoxication, was progressively inhibited, indicating that those muscles still delivered soman into the incubation medium. In rats, PDP (6.4 mg kg−1 i.v.) pretreatment was effective in preventing inhibition of intravenously injected electric eel AChE 1.5 h after intoxication with a high dose of soman (330 μg kg−1). But after intoxication with a low dose (172.5 μg kg−1), PDP pretreatment was ineffective in this action, however, it did lead to less soman delivery from muscle tissue isolated 30 min following the 172.5 μg kg−1 soman intoxication, suggesting that there was less soman in the tissue. In PDP (6.4 mg kg−1 i.v.)-pretreated marmosets (100 μg kg−1 soman) and guinea-pigs (150 μg kg−1 soman), to the contrary, the trend was for the injected AChE to be more inhibited, whereas only slightly less soman was delivered from isolated muscle tissue. It is suggested that after PDP treatment to rats the elimination of soman from the blood circulation is faster than in marmosets and guinea-pigs.
Enantiomer resolution of nefopam hydrochloride, a novel analgesic: a study by liquid chromatography and circular dichroism spectroscopy
Authors: Isaksson Roland , Sandström Jan , Eliaz Michal , Israely Zehorith , Agranat Israel 
Published: April 2011

Abstract
Nefopam, a potent analgesic, has been completely resolved into enantiomers on a preparative scale by low-pressure liquid chromatography on swollen, microcrystalline triacetylcellulose. The enantiomerically pure hydrochlorides were prepared from the base, and the circular dichroism spectra of the free base and the hydrochloride are reported.
Stereoselectivity of κ-opiate receptor ligands in inhibiting the binding of [3H][3-MeHis2]thyrotrophin releasing hormone to brain membranes
Authors: Bhargava Hemendra N , Das Sumantra , Gulati Anil 
Published: April 2011

Abstract
The effect of (±)-, (−)- and (+)-isomers of several ligands for κ-opiate receptors on the binding of [3H][3-MeHis2]-thyrotrophin releasing hormone ([3H]MeTRH) to rat brain membranes has been determined. [3H]MeTRH bound to rat brain membranes at a single high affinity site with maximal binding capacity (Bmax) of 48 ± 2 fmol(mg protein)−1, and an apparent dissociation constant, Kd of 4.6 ± 0.2 nM. At a concentration of 2 nM, the specific binding of [3H]MeTRH was 12.3 ± 0.6 fmol(mg protein)−1. The isomers of ketocyclazocine, tifluadom (1-methyl-2-(3-thienylcarbonyl) aminomethyl-5-(2-fluorophenyl) H-2,3-dihydro-1,4-benzodiazepine), and α-5,9-diethyl-2′-hydroxy-2-(3-furylmethyl)-6,7-benzomorphan [MR 2266 (−), MR 2267 (+)] were used for interaction studies. The (−)-isomer of each of the above drugs was more potent than the (+)-form in inhibiting the binding of [3H]MeTRH to brain membranes, whereas the (±)-forms had activity intermediate between (−)- and (+)-forms. The order of activity of κ-ligands was tifluadom &gt; MR 2266 &gt; ketocyclazocine. It is concluded that κ-opiate drugs inhibit the binding of [3H]MeTRH to brain membranes in a stereoselective manner with tifluadom being the most potent drug.
Structure-activity relationship of hylambatin and its fragments as studied in the guinea-pig ileum
Authors: Inoue A , Fukuyasu T , Nakata Y , Yajima H , Nomizu M , Inagaki Y , Asano K , Segawa T 
Published: April 2011

Abstract
Hylambatin (Hyl), a dodecapeptide isolated from the skin of the African frog, Hylambates maculatus, belongs to the family of tachykinin or physalaemin-like peptides. Hylambatin and its 12 fragments were tested in the guinea-pig ileum preparation for contractile activities. All fragments except 3 had contractile activities. The C-terminal fragment as short as the octapeptide sequence was at least as active as the parent molecules. The heptapeptide fragment (Hyl6-12) and the hexapeptide fragment (Hyl7-12) were less active and the C-terminal pentapeptide fragment (Hyl8-12) and the N-terminal hexapeptide fragment (Hyl1-6) were much less active. The N-terminal pentapeptide fragment (Hyl1-5) and the N-terminal fragment from which the N-terminal Asp or Asp-Pro residues were removed (Hyl2-6, Hyl3-6), were inactive at doses used.
The discrimination between human, porcine and bovine insulin with 1H NMR spectroscopy
Authors: Funke Carel W , Mellema Jan-Remt , Salemink Paul , Wagenaars Gerard N 
Published: April 2011

Abstract
The 1H- and 1H-1H correlation (COSY) NMR spectra of human, porcine and bovine insulin have been recorded. The 1.1–1.5 ppm regions of these spectra show the methyl signals of the alanine and threonine residues. The number of alanines and threonines differs for the three insulins and thus allows an easy discrimination with NMR.
Antidiarrhoeal activity of bisnordihydrotoxiferine isolated from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae)
Authors: Melo Margareth de F F , Thomas G , Mukherjee R 
Published: April 2011

Abstract
Bisnordihydrotoxiferine, a dimeric tertiary indole alkaloid obtained from the root bark of Strychnos trinervis (Vell.) Mart. (Loganiaceae), inhibited normal defaecation and castor oil, arachidonic acid, and magnesium sulphate-induced diarrhoea on intraperitoneal administration in mice. The effect may be related to the ability of the compound to decrease normal and castor oil-stimulated gastric emptying, small intestinal transit and water and electrolyte accumulation, and inhibition of normal colonic transit. As prostaglandins are involved in gastrointestinal functions, inhibition of their synthesis is likely to contribute to the anticathartic activity, which has never been reported before for an indole alkaloid.
Interaction of Memantine with Cholecystokinin Receptors in Mouse Brain
Authors: Verspohl E J , Koch R , Schatton W 
Published: April 2011

Abstract
The effect of memantine on CCK receptors in mouse brain has been investigated using particles of dissected cortex and striatum. Total binding of radio-labelled CCK33 was one-half maximal within 10 min of incubation and reached a maximum after 30 to 60 min when either cortex or striatum was used. Non-specific binding (presence of 100 μM unlabelled CCK8) was 50 to 80% of total binding at steady state conditions. CCK8 inhibited specific binding of radiolabeled CCK33 in a dose-dependent manner; the IC50 (half-maximal inhibitory concentration) was in the range 3 to 4 nM. Memantine increased CCK binding in a concentration-dependent manner, though at high concentrations. The EC50 (half-maximal effective concentration) of this effect was &lt; 100 μM. The memantine effect is not due to an inhibition of labelled CCK degradation in the medium. The effect of memantine on CCK binding is unique for brain since it was not observed in pancreatic acinar membranes. These data, therefore, suggest a modulatory effect of memantine on CCK receptors in mouse brain (cortex and striatum) particles.
Agonist profile of ergometrine (ergonovine) on a population of postsynaptic α-adrenoceptors
Authors: Gibson A , Carvajal A 
Published: April 2011

Abstract
Ergometrine (0.02–5 μM) produced concentration-related contractions of the mouse anococcygeus muscle, which were unaffected by cocaine (2 μM) or by pretreatment of mice with 6-hydroxydopamine. Contractions were reduced by α-adrenoceptor antagonists; the rank order of potency was prazosin &gt; phentolamine &gt; yohimbine. With phenoxybenzamine as antagonist, the estimated dissociation constant (KD) for ergometrine was 0.41 μM. It is concluded that ergometrine causes direct activation of postsynaptic α1-adrenoceptors, and it is suggested that it acts on the same subtype of the receptor as imidazoline agonists.
Action of mefloquine on toad isolated rectus abdominis muscle
Authors: Lee H S , Go M L 
Published: April 2011

Abstract
The effects of mefloquine and quinine on acetylcholine-induced contractures of the toad rectus abdominis muscle have been investigated. Both drugs depressed acetylcholine-induced contractures in a dose-related and non-competitive manner. A partial reversal of the block was observed in the presence of 4-aminopyridine(10, 50 μM) and increased Ca2+ content (1.25 ×) of the Ringer solution. In both cases, the mefloquine-induced blockade was more readily reversed than that induced by quinine. Mefloquine and quinine at concentrations greater than 100 and 500 μM, respectively, also elicited a direct contractile response on the muscle. Quantitative differences in their contractile activity have been attributed to the greater lipid solubility and tissue binding affinity of mefloquine.
A selective inhibitor of cAMP-specific phosphodiesterase, Ro 20–1724, has no effect on the quantal release of acetylcholine from the mouse phrenic nerve
Authors: Chiou L C , Chang C C 
Published: April 2011

Abstract
The indirect twitch response of the mouse isolated phrenic nerve-diaphragm preparation, partially paralysed by tubocurarine, was restored only by about 10% by Ro 20–1724 at 2 to 280 μM. The solvent vehicle, dimethylsulphoxide, also showed the same effect to a similar extent. Intracellular recordings with glass microelectrodes revealed that Ro 20–1724 (40 μM) affected neither the resting membrane potential, the amplitude and frequency of miniature endplate potentials nor the amplitude of nerve-impulse evoked endplate potentials recorded in curarized preparations. The result indicates that Ro 20–1724 at a concentration four times the IC50 of phosphodiesterase inhibition has no effect on the quantal release of acetylcholine from a mammalian motor nerve and suggests that cAMP has no modulatory effect on the transmitter release.
N-Methylation of nicotine enantiomers by human liver cytosol
Authors: Crooks Peter A , Godin C Steven 
Published: April 2011

Abstract
Incubation of human liver cytosol with either R-(+)-[3H-N′CH3]nicotine or S-(−)-[3H-N′CH3]nicotine results in the formation of the corresponding N-methyl quaternary ammonium metabolite. A substrate stereoselectivity was observed in that the turnover number for the methylation of the S-(−)-isomer was 0.25 pmol mg 1 protein h−1, whereas that for the R-(+)-isomer was 2.11. The latter substrate exhibited an apparent Km value of 20.1 μM. Nicotine N-methylation appears to be species-dependent, since rat liver homogenates contained no ‘nicotine N-methyl-transferase’ activity, whereas with guinea-pig liver homogenates, a substrate specificity for only R-(+)-nicotine was observed.
Measurement of 5-Hydroxytryptamine Turnover Rate in Rat Cerebral Arteries
Authors: Soto Juan C , Marco Emilio J 
Published: April 2011

Abstract
Two methods for assessing 5-hydroxytryptamine (5-HT) turnover rate have been tested in the cerebral vessels of the rat. The pretreatment of the animals with benserazide 45 min before death brought about an increase in the levels of 5-hydroxytryptophan (5-HTP). When the MAO inhibitor pargyline was injected and the animals killed at different times, there was an exponential decrease in the concentration of 5-hydroxyindole acetic acid (5-HIAA) with time, whereas the increase in 5-hydroxytryptamine was linear only during the first 30 min, thereafter reaching a plateau. This pattern was similar to that obtained in the caudate nucleus after MAO blockade. In the hippocampus, pargyline induced a lineal accumulation of 5-HT throughout the experiment as well as an exponential decay of the 5-HIAA concentration. These results indicate that the turnover rate of 5-HT can be appraised in the rat cerebral arteries either after the rate of disappearance of 5-HIAA or from the accumulation rate of 5-HTP.
Paroxetine, a Selective 5-Hydroxytryptamine Uptake Inhibitor with Antidepressant Properties, Lacks Amphetamine-like Stimulus Properties in an Operant Drug Discrimination Bioassay in Rodents
Authors: Goudie A J , Dubicki W , Leathley M 
Published: April 2011

Abstract
To evaluate whether the novel antidepressant paroxetine has any possible amphetamine-like actions, rats were trained to discriminate (+)-amphetamine sulphate in a standard two lever operant drug discrimination (DD) procedure using a fixed ratio 10 schedule of food reinforcement with a quantal, lever selection, index of the amphetamine stimulus. The ‘training’ dose of amphetamine was 1 mg kg−1, i.p. Rats trained with this dose of amphetamine (n = 15) learned the drug discrimination rapidly over 30 training sessions and discriminative performance in these animals was subsequently maintained at a high level of accuracy (90% correct) over a prolonged time. In tests in these trained animals, amphetamine itself and the antidepressant agents nomifensine and tranylcypromine all produced clear, unequivocal dose-related generalization to amphetamine with ED50s of 0.2, 0.5 and 1.6 mg kg−1 respectively (as determined by probit analyses). In tests with paroxetine hydrochloride it was established that, over the dose range 0.3 to 10 mg kg−1, no evidence was seen of generalization to the amphetamine stimulus. These data confirm earlier studies which suggested that some antidepressants may possess abuse potential because of their ability to induce amphetamine-like internal states. In contrast, paroxetine is devoid of such properties.