bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of chronic bisacodyl treatment on the effect of acute bisacodyl on water and electrolyte transport in the rat colon
Authors: Beubler E 
Published: April 2011

Abstract
Excessive or unnecessary taking of laxatives leads to a vicious circle with perpetuation of laxative abuse and increase of laxative dosage, accompanied by severe clinically evident disturbances. It was investigated in rats whether chronic administration of bisacodyl reduces the effects of acute bisacodyl administration on net water and electrolyte flux in the rat colon transport in-vivo. After chronic pretreatment with bisacodyl had been given for 21 days (3 mg and 10 mg kg−1 day−1), net water and sodium absorption was found to be decreased whereas potassium secretion was increased. After 21 days of pretreatment, the effect of acute bisacodyl (10 μg ml−1 intraluminal) on net water and sodium transport was reduced whereas the effect on potassium secretion remained unchanged. Serum and erythrocyte levels of sodium and potassium remained unchanged in chronically pretreated rats. Serum aldosterone levels were enhanced two fold. It is concluded that under the experimental conditions described, chronically administered bisacodyl leads to elevated serum aldosterone which counteracts the effect of bisacodyl on net water and sodium transport but acts synergistically with bisacodyl on the effect on potassium loss.
Cocaine-like action of diphenhydramine in cat cerebral arteries
Authors: Balfagón Gloria , Marco Emilio J 
Published: April 2011

Abstract
Diphenhydramine (5.3 times 10−7 M) significantly reduced the tritium efflux evoked by 10 −7 M tyramine from cat cerebral arteries preloaded with [3 H]noradrenaline but not that brought about by 50 mM KCl. These results indicate the ability of diphenhydramine to block the amine neuronal uptake.
Cardiac reactivity in rats with acute renal failure
Authors: Yates M S , Critchley M A , Askey Elizabeth A , Bowmer C J 
Published: April 2011

Abstract
Cardiac reactivity has been determined in rats with acute renal failure (ARF) induced by either bilateral nephrectomy or intramuscular glycerol injection. Rats with bilateral nephrectomy showed reduced chronotropic responses to cervical sympathetic stimulation but no appreciable alteration in the chronotropic responses to vagal stimulation. By contrast, we have previously noted that rats with glycerol-induced ARF show diminished chronotropic responses to stimulation of both nerves. The negative chronotropic and inotropic responses to carbachol in isolated atria from both nephrectomized and glycerol-injected rats were not significantly different from their respective controls. In both models of ARF the atrial positive chronotropic responses to isoprenaline were significantly decreased whilst positive inotropic responses were not significantly different from controls. The results indicate that the cause of the reduced chronotropic response to vagal stimulation observed in glycerol-injected rats is of presynaptic origin whilst the reduced chronotropic response to cervical sympathetic stimulation noted in both models of ARF may be due to an impaired postsynaptic response.
Characterization of [3 H]zetidoline binding to rat striatal membranes
Authors: Barone Domenico , Assandri Alessandro , Galliani Giulio , GläSser Alfredo , Tarzia Giorgio 
Published: April 2011

Abstract
The binding of [3 H]zetidoline, a novel neuroleptic agent, to rat brain striatal membranes was investigated in-vitro. The optimal binding conditions for [3 H]zetidoline differed from those for [3 H]spiperone in pH, temperature and time. [3 H]Zetidoline has high affinity for striatal dopamine receptors. Its binding is saturable, stereo-specific, has a low non-specific component and is reversible and tissue specific. The Scatchard analysis gave a biphasic curve, indicating that [3 H]zetidoline interacts with more than one population of receptor sites (B'max = 67 fmol mg−1 protein, K'd = 0.11 nM; B”max = 500 fmol mg−1 protein, K'd = 2.49 nM). Kinetic analysis of rates of association and dissociation yielded a Kd value in agreement with that measured at equilibrium. Inhibition studies indicated that only dopamine and dopaminergic agents are able to displace [3 H]zetidoline from its binding sites, and in a different rank order from that for displacement of [3 H]spiperone. (-)-Sulpiride was especially effective in inhibiting [3 H]zetidoline specific binding. Furthermore, like that of [3 H]benzamides, [3 H]zetidoline binding appears to be highly Na+ -dependent and Li+ only partially substitutes Na+.
Evidence for the involvement of endogenous substance P in the motor effects of capsaicin on the rat urinary bladder
Authors: Maggi Carlo Alberto , Santicioli Paolo , Meli Alberto 
Published: April 2011

Abstract
[pro4, trp7,9, Leu11]SP-(4−11), a substance P(SP) antagonist, selectively antagonized contractions produced by either capsaicin or SP on the rat isolated urinary bladder. These experiments provide direct evidence indicating that the motor effects of capsaicin on rat urinary bladder are attributable, at least in part, to the release of endogenous SP.
Effect of verapamil and diltiazem on isolated gastro-oesophageal sphincter of the rat
Authors: Morales-Olivas Francisco J , Cortijo Julio , Esplugues Juan Vicente , Rubio Elena , Esplugues Juan 
Published: April 2011

Abstract
The effect of verapamil and diltiazem on the contraction induced by agonists on the rat lower oesophageal sphincter in-vitro has been studied. Both calcium entry blockers inhibited the contractile response to acetylcholine, carbachol and KCl. The potency of the inhibitory action was diltiazem &gt; verapamil. The results give substance to the use of calcium entry blockers in the treatment of oesophageal spasm.
Influence of surfactant-treated starch on the disintegration and dissolution of sulphadiazine tablets
Authors: Nasipuri R N , Omotosho J A 
Published: April 2011

Abstract
The effects of treating cassava starch with sodium lauryl sulphate and Polysorbate 80 and the method of incorporating the treated and plain starch as disintegrant on the physical properties of sulphadiazine tablets were investigated. Disintegration and dissolution rates were faster with starch in which surfactant was incorporated in dry state than with starch treated with solution of surfactant. A direct correlation was observed between the Hardness-Friability Index and T90 values. Polysorbate 80-treated starch exhibited a better dissolution profile than SLS-treated starch.
Metronidazole-induced myocardial depression: chemical and pharmacological studies on the role of calcium in-vitro
Authors: Essien E E , Femi-Onadeko B , Ojewole J A O 
Published: April 2011

Abstract
The interaction of metronidazole with calcium to form a water-soluble complex has been studied by titration with ethylenediaminetetraacetate (EDTA), direct current and pulse polarographic reduction steps of the nitro-group at pH 5 and 7, and by ultraviolet absorption. Stoichiometric calculations, X-ray powder diffraction pattern of the synthesized metronidazole-calcium complex, and molecular ion peak at m/z 381 in the mass spectrum of this product, showed that a 2: 1 complex is formed. The interaction of metronidazole with calcium on myocardial contractile performance of guinea-pig electrically-driven isolated left atria in physiological solution was also examined. Metronidazole induced a sustained, concentration-dependent depression of the tension that was reversed by changing the bathing fluid to physiological solution, and/or by adding excess calcium ion. The drug-induced negative inotropic response was antagonized competitively by increasing calcium ion in the bath, whereas noradrenaline antagonized metronidazole-induced negative inotropic responses non-competitively. Addition of the metronidazole-calcium complex to the bath did not affect normal myocardial contractile performance. The results show that metronidazole produces a direct negative inotropic effect on isolated atrial muscles by interfering with Ca2+, and by preventing Ca2+ function in the events leading to contractile activity of atrial muscles.
Reflectance measurements on gels and emulsions containing cetrimide and cetostearyl alcohol–-a preliminary investigation
Authors: Rowe R C , Patel H K 
Published: April 2011

Abstract
Various light scattering properties–-the reflectivity, contrast ratio and scattering index of a series of gels and emulsions containing cetrimide, cetostearyl alcohol, water and liquid paraffin have been examined using reflectance measurements made at 560 nm using a four-filter, tristimulus colorimeter. The scattering properties of both systems were dependent on the total interfacial surface area of either the dispersed unreacted cetostearyl alcohol and/or the dispersed droplets of liquid paraffin, and hence increased with increasing concentration of both ingredients. For the emulsion containing liquid paraffin, the scattering properties increased linearly with the concentration of liquid paraffin but with the ternary gel system the scattering properties were not directly related to cetostearyl alcohol concentration. This was confirmed by microscopy as due to the changes in the size of the dispersed unreacted cetostearyl alcohol. The results illustrate the potential of this simple, reproducible non-destructive technique in the study of the structure of such systems.
Changes in the disposition of promethazine during multiple dosing in the rabbit
Authors: Taylor G , Houston J B 
Published: April 2011

Abstract
During a multiple dosing regimen, the area under the promethazine blood concentration-time profile progressively decreased indicating auto-induction of metabolism. The increase in promethazine clearance (mean 35%) was not reflected in changes in either elimination half-life or minimum blood concentrations during the dosing interval. This was attributed to a deep compartment in the disposition of promethazine in the rabbit. The changes in promethazine clearance were accompanied by proportionally larger changes in the clearance of the monodesmethylpromethazine metabolite. The effect of promethazine pretreatment on the clearance of antipyrine was also studied and was found to be significantly increased by a mean of 17% following pretreatment with promethazine. However, the changes in the clearance of antipyrine did not highly correlate with those of promethazine and monodesmethylpromethazine. This may indicate that promethazine induces metabolic systems in the rabbit for which antipyrine is not a good substrate.
Effects of acute and chronic treatment on the pro-and anti-convulsant actions of CL 218, 872, PK 8165 and PK 9084, putative ligands for the benzodiazepine receptor
Authors: File Sandra E , Wilks Lucy 
Published: April 2011

Abstract
CL 218, 872 is a triazolopyridazine that acts at the benzodiazepine binding site. At low doses (0.5−7.5 mg kg−1) it is proconvulsant when combined with subconvulsant doses of picrotoxin but not when combined with pentetrazol (leptazol, pentylenetetrazol). At high doses (20−60 mg kg−1) CL 218, 872 counteracted seizures caused by pentetrazol but not those caused by picrotoxin. There was tolerance to the proconvulsant effects after five days of treatment and to the anticonvulsant effects after 15–20 days. Two phenylquinolines, PK 8165 and PK 9084, that also act at the GABA-benzodiazepine receptor complex have proconvulsant actions in combination with picrotoxin. Significant tolerance to these effects had not developed even after 20 days of treatment. It is concluded that three different sites on the GABA-benzodiazepine complex mediate the pro- and anti-convulsant actions of CL 218,872 and the proconvulsant actions of PK 8165 and PK 9084.
Comparison of (β-adrenoceptor populations in cat and guinea-pig left atria
Authors: Molenaar Peter , Mcpherson Grant A , Malta Errol , Raper Colin 
Published: April 2011

Abstract
The subtypes of β-adrenoceptor present in left atrial preparations from the guinea-pig and cat have been assessed using both responses obtained in organ bath experiments and radioligand binding studies. From the positive inotropic responses to procaterol, the pKB values for practolol using a variety of agonists, and from displacement of [125 I]cyanopindolol from left atrial membrane homogenates by the selective β1 and β2-adrenoceptor antagonists L643, 717-01J10 and ICI 118, 551, it was concluded that guinea-pig left atria possess only β1-adrenoceptors, whilst cat left atria possess both β1- and β2-adrenoceptor subtypes.
Cardiovascular effects in the Sprague-Dawley rat of 8−hydroxy−2(di- N-propylamino) tetralin, a selective 5−hydroxytryptamine receptor agonist
Authors: Gradin K , Pettersson A , Hjorth S , Hedner T , Arvidsson L E , Persson B 
Published: April 2011

Abstract
The intravenous administration of 8−hydroxy−2(di-N-propylamino) tetralin, a selective 5−HT receptor agonist, caused a biphasic blood pressure response and bradycardia in Sprague-Dawley rats. The initial pressor response involved peripheral α1-adrenoceptors since it was present in pithed rats and was antagonized by prazosin. Though the intracerebroventricular route of administration was not more effective the hypotension and bradycardia were probably of central origin. The bradycardia was prevented by pretreatment with atropine and propranolol suggesting an involvement of vagal as well as sympathetic activity. These results support the view that central 5−HT receptor activation reduces the blood pressure and heart rate.
The absorption of β-adrenoceptor antagonists in rat in-situ small intestine; the effect of lipophilicity
Authors: Taylor David C , Pownall Rowena , Burke Wendy 
Published: April 2011

Abstract
The absorption of β-adrenoceptor antagonists in rat in-situ small intestine; the effect of lipophilicity
Intestinal absorption characteristics of eleven β-adrenoceptor antagonists were measured by monitoring their disappearance from in-situ intestinal loops in the anaesthetized rat. All have basic pKa values of around 9.5 (with the exception of sotalol) but show a wide range of lipophilic character (octanol-water log P values from −0.79 to 3.65). The results show two types of absorption behaviour, indicating different mechanisms for ‘hydrophilic’ and ‘lipophilic’ β-adrenoceptor antagonists. The four most hydrophilic molecules (sotalol, atenolol, nadolol and practolol) show virtually identical absorption rate constants. Absorption is slow and relative rates in jejunum (mean pH 6.5) and ileum (mean pH 7.3) are not consistent with pH-partition (jejunum &gt; ileum). The more lipophilic members of the series (pindolol, timolol, metoprolol, oxprenolol, alprenolol and propranolol) are all absorbed much more rapidly. Absorption rate constant rises rapidly with log P and the expected pH effects are seen (ileum &gt; jejunum). Acebutolol shows anomalously slow absorption for its log P value.
Fat contents of meals and bioavailability of griseofulvin in man
Authors: Ogunbona F A , Smith I F , Olawoye O S 
Published: April 2011

Abstract
The bioavailability of griseofulvin was followed in twelve healthy volunteers by measuring the urinary excretion of the major metabolite 6-demethylgriseolfulvin, after each volunteer had ingested one 500 mg griseofulvin tablet under (1) fasting conditions, (2) immediately after a typical low-fat and (3) high-fat Nigerian meals. An increase of about 70 and 120% absorption occurred with the ingestion of the low-fat and high-fat meals respectively compared to the fasting state (P &lt; 0.01). The maximum excretion rates of the free metabolite (Vmax.) were also significantly increased (P &lt; 0.01) following consumption of low and high fat meals. Our results thus suggest that the higher the fat content of the meals the higher the enhancement of the bioavailability of griseofulvin in man.
Protein binding of disopyramide–-displacement by mono -N-dealkyldisopyramide and variation with source of α-1-acid glycoprotein
Authors: Haughey David B , Steinberg Irving , Lee Min Hwa 
Published: April 2011

Abstract
The binding of disopyramide to human serum proteins and human α-l-acid glycoprotein (AAG) was determined over a wide drug concentration range. Addition of 3.7 times 10−5 mol litre−1 mono- N-dealkyldisopyramide caused a 20–100% increase in disopyramide free fraction. The disopyramide free fraction in AAG solutions prepared from various commercially available sources of α-l-acid glycoprotein varied up to 2.5 fold at corresponding disopyramide concentrations. Pronounced differences in the calculated binding constants (affinity and capacity) were observed among the commercially available AAG preparations. These findings suggest that binding studies should be performed in appropriately harvested human serum or plasma to avoid possible artifacts associated with the use of commercial preparations of α-l-acid glycoprotein for binding studies.
An allylamine derivative (MDL 72145) with potent irreversible inhibitory actions on rat aorta semicarbazide-sensitive amine oxidase
Authors: Lyles Geoffrey A , Susan Fitzpatrick C M 
Published: April 2011

Abstract
(E)-2-(3, 4-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) was found to be an extremely potent inhibitor of the semicarbazide-sensitive amine oxidase (SSAO) in rat aorta homogenates. Considerable inhibition, which was not reversed by dialysis, could be produced under appropriate in-vitro conditions at drug concentrations around 10 nM. The pseudo first order kinetics for time-dependent inhibition by MDL 72145 (10–100 nM) were found to be consistent with a bimolecular reaction between enzyme and inhibitor with a rate constant for this step of 2 times 106 min−1 M−1. A similar rate of inhibition under an oxygen atmosphere to that obtained under nitrogen was produced upon incubation of enzyme with inhibitor, suggesting that oxidation of the inhibitor to an active metabolite was not required for its activity. Incubation of homogenates for very short periods (1 min) with inhibitor (0.05-0.5 μM) and benzylamine (1–10 μM) as substrate indicated non-competitive kinetics for the early interaction of enzyme with the drug. Benzylamine (50 μM), but not pyridoxal phosphate (100 μM), was able to protect SSAO from inhibition by 10 nM MDL 72145. However, pyridoxal phosphate alone appeared to produce some irreversible inhibition of the enzyme. Dialysis against buffer containing 50 μM or 1 mM benzylamine was unable to reactivate SSAO inhibited by 10 nM MDL 72145. It is concluded that MDL 72145 irreversibly inhibits SSAO by acting at, or near, the substrate binding site, but the exact nature of the complex formed remains to be identified.
Modulation of substance P-induced bronchoconstriction by lipoxygenase metabolites
Authors: Stewart A G , Thompson D C , Fennessy M R 
Published: April 2011

Abstract
In anaesthetized, mechanically ventilated guinea-pigs, substance P induces a bronchoconstrictor response comprising increases in airway resistance and decreases in dynamic compliance. Eicosatetraynoic acid (ETYA, 20 mg kg−1 i.v.) or BW755c (20 mg kg−1 i.v.) potentiated the substance P-induced bronchoconstriction. Neither indomethacin (1 or Smgkg-' i.v.) nor aspirin (20 mg kg−1 i.v.) significantly altered the potency of substance P on bronchomotor responses. These observations are consistent with the existence of a bronchodilator lipoxygenase metabolite(s).
The mouse anococcygeus muscle as a preparation for the bioassay of oxytocin
Authors: Botting J H , Gibson A 
Published: April 2011

Abstract
Oxytocin (0.1–10 nM) caused reproducible, dose-related contractions of the male mouse anococcygeus. Desensitization was not a major problem. The muscle was shown to be a useful oxytocin bioassay preparation, having a good index of precision (0.04).
Monoamine oxidase-A selective inhibition in human hypothalamus and liver in-vitro by amiflamine and its metabolites
Authors: Tipton Keith F , O'Carroll Anne-Marie , Mccrodden John M , Fowler Christopher J 
Published: April 2011

Abstract
Amiflamine (FLA 336(+)) and its two metabolites, FLA 788(+) and FLA 668(+) were found to be competitive inhibitors of the activity of monoamine oxidase-A in homogenates of human hypothalamus and liver obtained at autopsy. KI values, determined at pH 7.2, were 1.3,0.3 and 22 μM (liver) and 0.8, 0.2 and 14 μM (hypothalamus) for amiflamine, FLA 788(+) and FLA 668(+), respectively. Monoamine oxidase-B activity was only weakly inhibited by the compounds.
Dopamine receptor agonistic activities of R- and S-enantiomers of 4-hydroxy-2-di-n-propylaminoindan in cat hearts
Authors: Ilhan Mustafa , Flynn Jan R , Long John P , Bhatnagar R K , Cannon Joseph G 
Published: April 2011

Abstract
In-vitro and in-vivo studies were used to evaluate the presynaptic dopamine receptor stimulating activities of R-and S-enantiomers of 4-hydroxy-2-di-n-propylaminoindan in cat hearts. Bioassay results show that the R-enantiomer is 100 times more potent than the S-enantiomer in both in-vitro and in-vivo preparations.
Disposition of HI-6 oxime in rats after intravenous and intramuscular administration
Authors: Simons K J , Briggs C J 
Published: April 2011

Abstract
The pharmacokinetics of HI-6, a cholinesterase-reactivating oxime, were studied in rats, following intravenous or intramuscular administration. A two-compartment model was used to analyse the intravenous data and a one-compartment open model with first-order absorption was used for intramuscular data. Drug concentration had no influence on rate and extent of absorption of intramuscular injections, and bioavailability was 100%. Peak plasma concentrations of HI-6 occurred 15 min after intramuscular injection. No significant differences were found between mean values for half-life, plasma clearance, volume of distribution and area under the plasma concentration versus time curve for the two intramuscular doses and the intravenous dose used. Mean HI-6 plasma concentrations were 140.5 ± 4.2 μg ml−1 3 min after 20 mg ml−1 i.v., with a mean elimination half-life of 65.2 ± 21 min. Plasma clearance rate was 3.95 ± 0.93 ml min−1 kg and the apparent volume of distribution was 0.38 ± 0.17 litre kg−1. The oxime is rapidly distributed in and eliminated by rats when administered intravenously or intramuscularly.
Cocaine potentiates the responses to methacholine and noradrenaline in the rat vas deferens
Authors: Bradley Lynn , Doggrell Sheila A , Edmonds Sarah C 
Published: April 2011

Abstract
The ability of cocaine (10 μM) to potentiate the contractile responses of the epididymal half of the rat vas deferens to methacholine was reversed by prazosin. Prazosin also partially reversed the ability of cocaine to increase the spontaneous overflow of 3 H following loading of the tissue with [3 H]noradrenaline. We suggest that cocaine potentiated the responses to methacholine by stimulating, directly or indirectly, α1-adrenoceptors.
The interaction of Cimetidine with various antihypertensive agents in the spontaneously hypertensive rat
Authors: Dadkar N K , Aroskar V A , Gupte R D , Dohadwalla A N 
Published: April 2011

Abstract
The H2-receptor antagonist Cimetidine (250 μg) administered intracerebroventricularly (i.e.v.) 15 and 30 min before Clonidine (25 μg kg−1 i.v.), significantly antagonized clonidine-induced hypotension in anaesthetized spontaneously hypertensive rats. The hypertensive response of Cimetidine was correlated with the inhibition of clonidine-induced hypotension. In addition, Cimetidine (250 μg i.e.v.) counteracted the hypotensive effects of pentolinium (5.0 mg kg−1 i.v.), guanethidine (5.0 mg kg−1 i.v.) and minoxidil (1.0 mg kg−1 i.v.) These data do not support previous suggestions that the hypotensive action of Clonidine is caused by stimulation of the H2-receptor, but suggest that central administration of Cimetidine causes peripheral vasoconstriction and this may offer resistance to the hypotensive action of different antihypertensive agents.