bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid chromatographic retention of β-adrenoceptor antagonists: an index of lipid solubility
Authors: Arendt Rainer M , Greenblatt David J 
Published: April 2011

Abstract
The in-vitro lipophilicity of nine β-adrenoceptor antagonists was evaluated based on retention on a reverse-phase C−18 high-pressure liquid chromatographic (hplc) system at physiologic pH. Propranolol was by far the most lipophilic drug, while atenolol and sotolol were the least. Hplc retention was highly correlated (r = 0·92) with octanol: buffer partition coefficient. Thus hplc retention is a rapid and replicable approach to the determination of in-vitro lipophilicity that does not require radioactive drug.
The effect of week-long infusion of propranolol, via an osmotic minipump, on blood pressure, heart rate and vascular responses in spontaneously hypertensive rats
Authors: Sun Ching-Long J , Thompson Teresa J , Hanig Joseph P 
Published: April 2011

Abstract
Propranolol was infused in SHR subcutaneously for 7 days at two concentrations (either 3·75 or 7·5 mg kg−1 day) via a minipump. Mean blood pressure and heart rate measured under pentobarbitone anaesthesia on day 7 after implantation showed a significant dose-dependent decrease in both propranolol-treated groups. In the low-dose propranolol-treated rats, there was no change in contractile responses to phenylephrine over controls. In rats receiving the higher dose of propranolol there was a significant increase in the response to phenylephrine. There was no change in the relaxation response of any of the groups to isoprenaline. The results indicate that propranolol, while lowering blood pressure and heart rate, is also modifying the α-receptor response of the vascular wall in the spontaneously hypertensive rat.
5−Hydroxytryptamine desensitization fails to modify GABA-induced inhibitory responses in the guinea-pig colon
Authors: Onori L , Saltarelli P , Marcoli M , Lecchini S , Frigo G M , Tonini M 
Published: April 2011

Abstract
In segments of guinea-pig colon, treated with 1 μm hyoscine, a 5−HT desensitization procedure that decreased the potency of 5−HT 41−fold in relaxing the longitudinal musculature, failed to modify the non-adrenergic GABA-induced inhibitory responses, suggesting that the action of GABA in this preparation is not 5−HT-mediated. These results are at variance with those obtained in the guinea-pig ileum where 5−HT seems to play a role in GABA-induced cholinergic contractions.
Monoamine oxidase inhibition by the tremorogenic drug–-LON 954
Authors: Mitra C , Ganguly D K , Guha S R 
Published: April 2011

Abstract
N-Carbamovl−2−(2,6−dichlorophenyl)acetamidine HCl (LON 954), a tremorogenic drug, inhibited MAO activity in various tissue preparations in a reversible, competitive manner showing some degree of selectivity towards type-B MAO.
Effects of nomifensine and its metabolites on dihydropteridine reductase
Authors: Shen Rong-sen , Sheng Wen-Lu , Abell Creed W 
Published: April 2011

Abstract
Nomifensine and three of its metabolites were studied as potential inhibitors of dihydropteridine reductase. Purified enzyme preparations from human liver and the P2 fraction of rat striatal synaptosomes were used as enzyme sources. Nomifensine and its 3−hydroxyl derivative inhibit this enzyme from both sources at 1·3 to 3·5 times 10−4 m (150 values). 4−Hydroxylated nomifensines, however, non-competitively inhibited this enzyme with Ki values of 2·8 to 4·4 times 10−5 m. Dihydropteridine reductase regenerates tetrahydrobiopterin, the required cofactor for the hydroxylation of tyrosine and tryptophan, from quinonoid dihydrobiopterin. Inhibition of this enzyme could reduce the availability of the biopterin cofactor for the synthesis of dopamine and 5−hydroxytryptamine.
Nadolol binding to human serum proteins
Authors: Patel L , Johnston A , Turner P 
Published: April 2011

Abstract
Nadolol protein binding was measured in serum from 95 healthy subjects. Binding was found to range between 4 and 27%, with a mean of 14 ± 4% (s.d.). There was a small but significant correlation found between the degree of nadolol binding and the serum α-1−acid glycoprotein concentration. However it was concluded that changes in the serum protein binding of nadolol were unlikely to give rise to any untoward clinical effects.
The pharmacokinetic profile of carbidopa in dogs
Authors: Obach R , Menargues A , Vallès J M 
Published: April 2011

Abstract
A pharmacokinetic study of carbidopa in beagle dogs has been carried out after intravenous (4 mg kg−1) and oral (75 mg) administration. An open model of three compartments was the best approach for the pharmacokinetic profile of carbidopa administered intravenously. The estimated biological t1/2 was 5 h and the plasma clearance 0·0053 (litre kg−1) min−1. The oral absorption of carbidopa was almost complete and the absolute bioavailability (F) was 88%.
Preparation and evaluation of biodegradable polymeric systems for the intra-articular delivery of drugs
Authors: Ratcliffe J H , Hunneyball I M , Smith A , Wilson C G , Davis S S 
Published: April 2011

Abstract
Colloidal suspensions of four biodegradable polymers, polylactic acid (PLA), polybutylcyanoacrylate (PBCA), gelatin (PG) and albumin (PA) were prepared within the size range 1–10 μm. In-vivo biocompatibility tests with synovial tissues were carried out to assess the irritancy of the polymers following intra-articular injection into rabbit knee joints. PLA, PBCA and PG were found to cause joint inflammation whereas PA was well tolerated by the tissues. PA microspheres may provide a means of sustaining the release and reducing the rate of clearance of drugs from the knee joint.
Effects of diflunisal on fever in the rabbit and the rat
Authors: Dascombe M J 
Published: April 2011

Abstract
The antipyretic efficacy of diflunisal was assessed in rats made febrile by yeast and in rabbits made febrile by bacterial endotoxin. Diflunisal was a more potent antipyretic than aspirin in rats, reducing a maximum fever in doses not producing overt toxic effects. In contrast, submaximal fever in rabbits was not reduced by diflunisal. Fatal hyperthermia of rapid onset was observed in rats and rabbits receiving high doses of diflunisal after administration of microbial pyrogen but not in control animals. These data indicate the toxicity of diflunisal may be potentiated by the presence of pyrogens. It is concluded that the apparent antipyretic efficacy of a drug can depend on the species-pyrogen combination used to screen for antipyresis.
Triethylphosphine gold: Cellular uptake and disposition after single and repeated oral doses in rats
Authors: Sharma R P , Smillie J , Laverty R 
Published: April 2011

Abstract
The tissue and subcellular pharmacokinetics of gold following single and repeated oral doses of triethylphospine gold (auranofin) has been studied in rats. After a single dose, the tissue and subcellular gold levels were 5–10 times lower than those reached with injectable gold compounds. In the liver tissues, gold concentrations peaked within 24 h followed by a biphasic clearance, with an initial rapid phase (t1/2 32 h) and a slow terminal phase (t1/2 11 days). Renal gold concentrations continued to increase for 3 to 5 days and then decreased exponentially with a first order t1/2 of about 7 days. Intracellularly, between 60–80% of hepatic and 50–70% of renal gold was present in the cytosol. In rats given repeated doses of auranofin, the hepatic and renal gold concentrations were 3–5 times higher than those measured after a single dose. The proportion of cellular gold present in the cytosol was markedly lower, with 43% in the liver and 30% in kidney tissues. In both the liver and kidney, gold concentrations were dose-dependent, whereas in the gastrointestinal tissues the increases as a function of dose were minimal.
Effect of formulation on the bioavailability of retinol, d-α-tocopherol and riboflavine
Authors: Bateman N E , Uccellini D A 
Published: April 2011

Abstract
Formulation factors influencing vitamin bioavailability have been investigated, with vitamins A, E and B2, formulated in a new liquid vehicle (Aqua-Biosorb) and encapsulated into soft gelatin capsules, being compared with commercial formulations. There was an enhanced vitamin bioavailability from the new vehicle which appeared to be related to the surfactant system employed and the absence of vegetable oil in the formulation.
Covalent binding of antibodies to liposomes using a novel lipid derivative
Authors: Goundalkar Ashok , Ghose Tarun , Mezei Michael 
Published: April 2011

Abstract
N-[3−(2−Pyridyldithio) propionyl] stearylamine (PDP-SA) was synthesized from a reaction between stearylamine and the heterobifunctional reagent N-succinimidyl−3−(2−pyridyldithio) propionate. Use of this PDP-SA to covalently couple antibodies to liposomes was investigated. The binding efficiency was found to be 24–32%. The antibodies bound to liposomes were shown to retain the specific antibody activity. This new procedure of coupling antibodies to lipsosomes could be an efficient means to deliver drugs to selected target organs, especially in cancer chemotherapy.
Is the hypothermic effect of α-methyldopa mediated by opioid peptides?
Authors: Sitsen J M A , Nijkamp F P 
Published: April 2011

Abstract
At an ambient temperature of 21 °C α-methyldopa (25–200 mg kg−1) induces a dose-dependent decrease in body temperature in rats. A relationship between adrenergic and opioid neuronal systems has been reported. Therefore, in this study the hypothesis that α-methyldopa produces hypothermia through release of endogenous opioid peptides has been investigated using the opiate antagonist naltrexone. The hypothermic effect of α-methyldopa is potentiated by naltrexone pointing to antagonism of an hyperthermic acting opioid system. However, at an ambient temperature of 6 °C, pretreatment with naltrexone did not significantly alter the hypothermic effect of α-methyldopa. Although the hypothesis proved not to be correct, it is concluded that depending on ambient temperature opioid peptides are involved in the determination of the ultimate effect of α-methyldopa on body temperature in rats.
Dopamine receptor binding sites in the rat superior colliculus
Authors: Chivers J K , Hall M D , Kelly E , Jenner P , Marsden C D 
Published: April 2011

Abstract
Following intravenous administration of [3H]spiperone or [3H]N,n-propylnorapomorphine (NPA) to rats, radioactivity derived from the ligands accumulated in the striatum and superior colliculus when compared with cerebellar levels. The accumulation of [3H]spiperone in both areas was prevented by intraperitoneal administration of (+)-butaclamol, haloperidol and sulpiride but not by (-)-butaclamol, cinanserin, propranolol or prazosin. The accumulation of [3H]NPA was prevented by administration of (+)-butaclamol, haloperidol and apomorphine but not by (-)-butaclamol. In in-vitro experiments, membrane preparations from the superior colliculus showed a small number of specific binding sites for both [3H]spiperone and [3H]NPA. The dissociation constant (KD) for [3H]NPA was not different from that for striatal preparations but that for [3H]spiperone was 10−fold higher. We conclude that dopamine receptors may be present within the superior colliculus.
Effect of morphine on the tissue cyclic AMP and cyclic GMP content in two strains of mice
Authors: Muraki T , Uzumaki H , Kato R 
Published: April 2011

Abstract
The effect of morphine on the cyclic (c) AMP and cyclic (c) GMP concentrations in several organs, and its reversal by naloxone have been investigated in C57BL and DBA strains of mice. Morphine increased the cAMP contents in lungs and muscle, and the cGMP contents in lungs, intestine, heart, liver and muscle in a naloxone-reversible way in C57BL mice only. This is consistent with our previous observation that morphine increased plasma cyclic nucleotide levels in C57BL mice, whereas such an increase was marginal in the DBA strain. These results show that there is a strain difference in the effect of morphine on tissue cyclic nucleotide contents and the possible origin of the plasma cyclic nucleotides which are increased by morphine.
The action and interaction of β-phenethylamines and imidazolines on prejunctional α2-adrenoceptors of guinea-pig ileum in the presence of the non-competitive antagonist benextramine
Authors: Mottram D R , Thakar Y 
Published: April 2011

Abstract
The effects of benextramine, a selective non-competitive, irreversible antagonist of α-adrenoceptors, against α2-adrenoceptor agonists has been investigated in isolated field-stimualted guinea-pig ileum. Benextramine was equipotent against the imidazoline, clonidine and the thiazoloazepine B-HT920, however, higher concentrations of benextramine were required for an equivalent non-competitive antagonism of the β-phenethylamine, α-methylnoradrenaline. Using benextramine to differentially block the agonist effects of clonidine but not α-methylnoradrenaline it was shown that clonidine can competitively antagonize the effects of α-methylnoradrenaline. From these and previous results on the differential effects of imidazoline-like and β-phenethylamine-like drugs on α2-adrenoceptors, it is proposed that two distinct populations of these receptors exist.
Differential effects of 5-hydroxytryptaminergic antagonists upon apomorphine- and lergotrile-induced hypothermia and stereotyped behaviour in rats
Authors: Wade Rolin L , Quock Raymond M , Malone Marvin H 
Published: April 2011

Abstract
The dopaminergic stimulants apomorphine and lergotrile both evoked hypothermia and stereotyped behaviour in rats. These drug effects were sensitive to antagonism by haloperidol, a dopaminergic receptor blocker. In rats pretreated with 5-hydroxytryptaminergic receptor blockers, cinanserin reduced apomorphine-induced hypothermia but cyproheptadine did not. Both cinanserin and cyproheptadine significantly potentiated lergotrile-induced hypothermia. Similarly, the stereotypic effects of apomorphine were partly reduced by cyproheptadine, although higher doses of cyproheptadine did potentiate lergotrile-induced stereotyped behaviour. These findings of different influences of 5-HT antagonists upon the effects of apomorphine and lergotrile indicate that these two dopaminergic stimulants may not work in identical manner to produce outwardly similar drug effects.
An homogeneous population of β1-adrenoceptors subserves inhibitory responses in guinea-pig ileal preparations
Authors: Mian M Aqleem , Malta Errol , Raper Colin 
Published: April 2011

Abstract
In transmurally stimulated guinea-pig ileal preparations, the pA2 values obtained with the selective β1- and β2-adrenoceptor antagonists atenolol and ICI 118,551 were independent of the β-adrenoceptor agonist used ((-)-isoprenaline or fenoterol) and were similar to values reported in isolated cardiac tissue. On the basis of these results, the relaxant responses to β-adrenoceptor agonists in guinea-pig ileal preparations appear to be mediated by an homogeneous population of β1-adrenoceptors.
Central and peripheral inhibition of gastrointestinal transit in rats: narcotics differ substantially by acting at either or both levels
Authors: Peracchia Francesca , Bianchi Giancarlo , Fiocchi Roberto , Petrillo Paola , Tavani Alessandra , Manara Luciano 
Published: April 2011

Abstract
The roles of local intestinal and centrally mediated opiate-specific mechanisms underlying gastrointestinal transit inhibiton by five typical narcotic analgesics were assessed by the rat charcoal meal test. The doses (mg kg−1 s.c.) reducing the progression of charcoal to 50% of drug-free controls in 5 min (ID50) were approximately 1 for morphine and methadone, 0·5 and 40 for diamorphine and pethidine (all given 25 min before charcoal) and 0·001 for etorphine (10 min before charcoal). The delay in test meal travel caused by these ID50 doses was completely prevented by i.p. naloxone. Intracerebroventricular (i.c.v.) naloxone fully antagonized pethidine and etorphine but had no effect on morphine. Morphine, but either pethidine nor etorphine, was antagonized by i.p. N-methyl naloxone (a peripheral antagonist). Diamorphine and methadone were partially antagonized by i.c.v. naloxone or i.p. N-methyl naloxone.
Human angiotensin I competes with two non-thiol converting enzyme inhibitors (CGS 13934 & MK-422) to inhibit the angiotensin-converting enzyme activity of human plasma
Authors: Chen Dong-Sheng , Nussberger Jürg , Brunner Hans R , Waeber Bernard 
Published: April 2011

Abstract
A simple in-vitro enzyme system has been used to demonstrate that human angiotensin I interacts competitively with the two non-thiol converting enzyme inhibitors CGS 13934 and MK-422 to inhibit the hydrolysis of a synthetic substrate by human plasma ACE.
The effect of therapeutic agents on cartilage degradation in-vivo
Authors: Sedgwick A D , Moore A R , Sin Y M , Al-Duaij A Y , Landon B , Willoughby D A 
Published: April 2011

Abstract
Implantation of minced autologous cartilage into inflamed air pouches in mice allows the study of therapeutic agents on both the inflammatory process and cartilage degradation. Non-steroidal anti-inflammatory agents were found to reduce cell accumulation in response to carrageenan, but were unable to prevent proteoglycan loss from cartilage. In contrast. d-penicillamine had no effect on the inflammatory process but significantly reduced proteoglycan loss. Our findings suggest that the autologous cartilage transplantation model in the mouse may be useful for studying novel anti-arthritic agents.
A possible cytochrome P-450-mediated N-oxidation of diethylcarbamazine
Authors: Joseph C A , Dixon P A F 
Published: April 2011

Abstract
There was a marked sex difference in the N-oxidation of diethylcarbamazine (DEC) in the rat. In 72 h, 41 and 20% of the administered DEC was excreted in urine as the N-oxide in male and female rats respectively. Safrole, metyrapone and ethanol inhibited this N-oxide formation in male rats by 71, 37 and 44% whereas in female rats the values were 20, 25 and 0% respectively. Phenobarbitone and anthracene enhanced N-oxide formation in male rats by 17 and 20% and in female rats by 50 and 90% respectively, but the amount of the N-oxide formed was more in the males. The result suggests a possible involvement of a sub-population of cytochrome P-450 isozyme (which is more in male rats) in the N-oxidation of DEC.
The effect of in-vivo dispersion and gastric emptying on glibenclamide absorption from a novel, rapidly dissolving capsule formulation
Authors: Ganley J A , Mcewen J , Calvert R T , Barker M C J 
Published: April 2011

Abstract
The in-vivo dispersion and gastric emptying of a novel glibenclamide dose form have been investigated using γ-scintigraphy and related to the absorption of glibenclamide determined by measuring glibenclamide plasma concentrations. Its absorption is determined by the rate of emptying of the dose form from the stomach with the lag time between dosing and the start of gastric emptying (and hence absorption of the dose) largely dependent on the in-vivo disintegration time. The presence of food in the stomach has a marked effect on in-vivo disintegration/dispersion of the dose form and hence on the lag time between dosing and the start of absorption.
Anti-inflammatory action of drugs that raise adenosine-3′,5′-cyclic monophosphate and putrescine levels in-vivo
Authors: Hidir S Mohd , Lewis D A 
Published: April 2011

Abstract
Isoprenaline and salbutamol, two β-adrenoceptor agonist drugs, and 3-isobutyl-methyl xanthine and thioacetamide have been shown to be anti-inflammatory. Their mode of action is probably due to an increase in the levels of the three endogenous substances adenosine-3′,5′-cyclic monophosphate and putrescine and spermidine in-vivo.
Effect of central prostaglandins on carrageenan-induced pedal oedema in rats
Authors: Bhattacharya S K , Das Neeta 
Published: April 2011

Abstract
The possible modulatory effect of central prostaglandins (PGs) on carrageenan-induced pedal inflammation, was investigated in rats. Intracerebroventricularly (i.c.v.) administered arachidonic acid, the PG precursor, produced a statistically insignificant increase in the inflammatory response, though PG synthesis inhibitors, administered by the same route, markedly attenuated the oedema. Centrally administered PGE2 had a significant proinflammatory effect, whereas PGF2α exerted an antiinflammatory action. The results indicate that central PGs may modulate peripheral inflammation and that, at least partly, the anti-inflammatory activity of PG synthesis-inhibiting non-steroidal anti-inflammatory agents may involve central PGs, as has been proposed for their analgesic effect.
Scatchard plots with a positive slope: dependence upon ligand concentration
Authors: Clegg L Stephen , Lindup W Edward 
Published: April 2011

Abstract
The inverse dependence of binding constants (nK) upon albumin concentration for 2-(4′-hydroxybenzeneazo) benzoic acid (HABA) has been investigated with bovine and human albumin by equilibrium dialysis. Data obtained by the use of a range of concentrations of either bovine or human albumin, together with a single ligand concentration, gave positive Scatchard plots indicative of binding constants inversely dependent upon protein concentration. The slope of each plot was influenced by the particular ligand concentration used and an increase in the ligand concentration in the case of both bovine and human albumin resulted in a decrease in the slope of the positive Scatchard plot. Higher concentrations of ligand produced a transformation from a positive to a negative plot with both bovine and human albumin.
Evidence for a pharmacokinetic interaction between ibuprofen and meptazinol in the mouse
Authors: Stephens R J 
Published: April 2011

Abstract
Of a variety of non-steroidal anti-inflammatory drugs administered concurrently with meptazinol (p.o.), only ibuprofen potentiated the antinociceptive response (mouse, hot-plate test) to the opioid. In addition, the brain tritium concentration of mice given [3H]meptazinol (p.o. or i.v.) was significantly raised by the oral administration of ibuprofen. It is argued that the interaction between these drugs is pharmacokinetic in nature, due probably to an action of ibuprofen on the biotransformation of meptazinol.
Inhibition of semicarbazide-sensitive amine oxidase by monoamine oxidase B inhibitors from the oxazolidinone series
Authors: Dostert P , Guffroy C , Benedetti M Strolin , Boucher T 
Published: April 2011

Abstract
The purpose of the present work was to study the semicarbazide-sensitive amine oxidase (SSAO) inhibitory properties of MD 240931 and MD 240928 (the two enantiomers of MD 780236) as well as those of the corresponding primary amines, MD220662 and MD220661, in rat heart and aorta. MD 240928 and MD 240931 are rather weak SSAO inhibitors, MD 240931 being more potent than MD 240928. Of the four compounds studied, the most potent inhibitor of SSAO is MD 220662, its IC50 value ranging from 2·10−6 to 6·10−6m. The SSAO inhibitory potency of this compound does not change significantly with the time of preincubation in both the absence and presence of clorgyline (10−4m). MD 220661 is also an inhibitor of SSAO; however, its SSAO inhibitory potency, which without preincubation is comparable to that of MD 220662, does decrease with the time of preincubation to the same extent in both the absence and presence of clorgyline (10−4 m). These results suggest that MD 220661 is not only an inhibitor of SSAO, but is also a substrate of the enzyme.