bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of 5-hydroxytryptaminergic autoreceptors in the rat hypothalamus
Authors: COX BARRY , ENNIS CHRISTINE 
Published: April 2011

Abstract
5-hydroxytryptamine (5-HT) (3 × 10−9 to 10−6 M) produced a concentration-related inhibition of potassium-evoked tritium release from slices of rat hypothalamus preloaded with [3H]-5-HT. The response to 5-HT was unaffected by the presence of yohimbine (10−6 M), pimozide (10−7 M), domperidone (10−7 M) or tetrodotoxin (10−7 M), indicating that the response was not mediated via α1- or α2-adrenoceptors or dopamine receptors and that the receptors that were involved were located directly on the 5-HT nerve terminal. The 5-HT antagonist metergoline (10−8 to 3 × 10−7 M) produced a parallel rightward shift in the concentration-effect curve to 5-HT with no reduction in the size of the maximum response. The pA10 value for metergoline was 6.82 and the slope of the Arunlakshana-Schild plot was not significantly different from 1.0 indicating that it was a competitive antagonist. Methiothepin produced a similar effect to metergoline whilst cyproheptadine and methysergide were less potent as antagonists of 5-HT and were not competitive. Cinanserin was inactive. Thus we have characterized the 5-HT autoreceptor in the rat hypothalamus using a classical pharmacological approach and found that it has more in common with the autoreceptor which we have previously identified in the raphe nuclei of the rat than it has with the 5-HT receptor located on dopamine neuroterminals in the striatum.
Effects of solvent medium on solubility. A linear free energy relationship treatment
Authors: MANZO RUBEN H 
Published: April 2011

Abstract
Linear relationships exist between the logarithms of the solubility equilibria of structurally closely related compounds, as they vary with changes in solvent or solvent composition in water and water-like solvents, trie slope Py of these linear free energy relationships quantitatively accounts for the direction and intensity of the relative solubility variations due to medium effects. Results obtained by applying the concept to series of both p-hydroxy- and p-aminobenzoic esters, and α-aminoacids, are presented. These results are explained by a simple model in terms of solute-solvent interactions.
Particulate contamination of sterile syringes and needles
Authors: TAYLOR S A 
Published: April 2011

Abstract
Commercially available sterile needles and syringes have been examined for particulate contamination using the Hiac light blockage technique. The number of particles delivered was small compared with the total number permitted for large volume parenterals. Where syringes are used in particle counting techniques, the contribution of particles should be taken into account.
Analgesia and increases in limbic and cortical MOPEG-SO4 produced by periaqueductal gray injections of morphine
Authors: REIGLE THOMAS G , WILHOIT CANDIDA S , MOORE MELISSA J 
Published: April 2011

Abstract
Analgesia and changes in limbic and cortical concentrations of the major brain noradrenaline metabolite, 3-methoxy-4-hydroxy-phenylethylene glycol sulphate (MOPEG-SO4), were investigated in rats following the bilateral injection of morphine into the periaqueductal gray (PAG). Morphine, at a dose of 5 μg per bilateral site, produced a significant antinociceptive effect within 15 min of injection. This effect, as measured by the tail flick analgesic test, remained constant at a level of approximately 75% of the maximum for 60 min. Significant increases in limbic and cortical MOPEG-SO4 were also observed 15, 30 and 60 min after the 5 μg bilateral PAG injection of morphine. However, MOPEG-SO4 concentrations exhibited a sharp peak in both brain areas at 30 min. Analgesia and the regional increases in MOPEG-SO4 were antagonized by the prior systemic injection of naloxone (1 mg kg−1, i.p.). Thus, analgesia and increases in noradrenaline metabolism in two brain regions appear to be mediated by the specific activation of opiate receptors in the PAG. Although these findings indicate that brain noradrenergic systems may be involved in the mediation of morphine analgesia, the lack of a strict temporal relationship between antinociceptive action and increases in MOPEG-SO4, suggests that analgesia cannot be totally attributed to changes in brain noradrenergic transmission.
Pharmacological isolation of a single β-adrenoceptor subtype makes Schild plots which have slopes of 1 possible for selective β-adrenoceptor antagonists in carbachol-contracted guinea-pig trachea
Authors: TAYLOR SAMUEL E 
Published: April 2011

Abstract
The effects of selective β-adrenoceptor agonists and antagonists on isometric relaxation of carbachol-contracted, guinea-pig isolated trachea were studied. An attempt was made to pharmacologically isolate the β1- and β2-adrenoceptors by use of appropriate selective agonists and antagonists. The slopes of the Schild plots for butoxamine vs noradrenaline and terbutaline as well as for practolol vs terbutaline did not differ significantly from 1, the predicted value for a competitive antagonist acting at a single receptor type. These data differ from a previous report suggesting that slopes of less than 1 are characteristic for selective β-adrenoceptor antagonists in carbachol-contracted guinea-pig trachea. They support the hypothesis that the low slopes in this preparation are due to interaction of the agonist with both β1 and β2-adrenoceptors rather than the state of contraction of the trachea.
Contractile actions of lysophosphatidic acids with a chemically-defined fatty acyl group on longitudinal muscle from guinea-pig ileum
Authors: TOKUMURA A , FUKUZAWA K , TSUKATANI H 
Published: April 2011

Abstract
Various lysophosphatidic acids caused phasic contractions of longitudinal muscle from guinea-pig ileum, followed by rhythmical contractions of lower magnitude. Polyunsaturated lysophosphatidic acids were more potent than saturated lysophosphatidic acids. Among the lysophosphatidic acids tested, linolenoyl-lysophosphatidic acid was the most active, but its activity was about 3–5 times less than that of prostaglandin F2α. Contractile responses to various lysophosphatidic acids, were partially suppressed by tetrodotoxin, atropine and chlorpheniramine. In addition, lysophosphatidic acid-induced contractions were considerably reduced by pretreatment of the muscle with indomethacin.
Effect of nabumetone (BRL 14777), a new anti-inflammatory drug, on human platelet reactivity ex vivo: comparison with naproxen
Authors: NUNN BARBARA , CHAMBERLAIN P D 
Published: April 2011

Abstract
The effect of nabumetone (BRL 14777) on human platelet reactivity ex vivo was compared with that of naproxen at equitherapeutic doses in the same six subjects. Nabumetone had only a weak and equivocal effect on collagen-induced and second phase aggregation in response to adenosine diphosphate and adrenaline. After nabumetone, platelets fully aggregated in response to sodium arachidonate, though approximately twice as much was needed as on control occasions. Sodium arachidonate was unable to elicit a full aggregation response after naproxen. These results suggest that nabumetone may cause less interference with haemostasis than other non-steroidal anti-inflammatory drugs.
Physicochemical and in-vitro biological studies on the possible association between theophylline and ethylenediamine in solution
Authors: Cotgreave Ian A , Caldwell John 
Published: April 2011

Abstract
The possible association in solution between the components of aminophylline, theophylline and ethylenediamine, has been studied using physicochemical and biochemical techniques. Addition of ethylenediamine to solutions of theophylline caused characteristic changes in its u.v. and 13C-n.m.r. spectra, which were due solely to the pH change, and not to any molecular association between the molecules in solution. Both compounds crossed the erythrocyte membrane extensively from plasma or 0˙9% NaCl and had no influence on each other’s behaviour. Theophylline partitioned approximately equally between octanol and pH 7˙4 phosphate buffer, while ethylenediamine remained in the aqueous phase. Again, neither compound affected the properties of the other. Theophylline was reversibly bound to plasma protein, the extent of which was dependent upon the temperature used for equilibrium dialysis. However, ethylenediamine was not bound to plasma protein, and did not alter the binding of theophylline. These data show that the components of aminophylline behave independently in solution, and suggest that there is no association between theophylline and ethylenediamine in biological systems.
The purported dopamine agonist DPI inhibits [3H]noradrenaline release from rat cortical slices but not [3H]dopamine and [14C]acetylcholine release from rat striatal slices in-vitro
Authors: van Oene J C , Sminia P , Mulder A H , Horn A S 
Published: April 2011

Abstract
The effects of the purported dopamine (DA) receptor agonist (3,4-dihydroxyphenylimino)-2-imidazolidine (DPI) upon the in-vitro K+-induced release of [3H]DA and [14C]acetylcholine from rat neostriatal slices, and of [3H]noradrenaline from rat neocortical slices have been investigated and compared with those of the DA receptor agonist TL-99 and the α-adrenoceptor agonist clonidine, respectively. The rapid decomposition of the catechol compounds DPI and TL-99 in the Krebs-Ringer bicarbonate superfusion medium was shown to be inhibited by both the chelating agent EDTA and the reducing agent ascorbic acid. The results suggest that in-vitro DPI is unable to stimulate striatal DA receptors, whereas it is effective in stimulating cortical α2-adrenoceptors (EC50 = 61 nm). It is concluded that DPI should be considered as a mixed α1/α2-adrenoceptor agonist and that the designation of DPI as a DA receptor agonist should be abandoned.
Rheological and sedimentation studies on Instant Clearjel and Primojel suspensions
Authors: Sabra K , Deasy P B 
Published: April 2011

Abstract
The suitability of Instant Clearjel and Primojel for use as extemporaneous suspending agents has been investigated by continuous shear and creep analysis using a specially constructed air turbine viscometer. Aqueous dispersions of both of the modified starches exhibited non-Newtonian, pseudoplastic flow with little thixotropy and some irreversible shear breakdown. Apparent viscosities, determined from the apices of flow curves obtained at constant maximum shear rate, decreased progressively with increase in temperature over the range 10–50 °C. An Arrhenius plot gave a low apparent activation energy of flow for Primojel. The two modified starches showed a marked rise in apparent viscosity with rise in pH from 3 to 11 of the dispersion medium. Only Instant Clearjel dispersions exhibited a linear viscoelastic region in creep testing, studies which confirmed that this system behaved as a viscoelastic liquid. Sedimentation studies on 10% w/v sulphadimidine suspensions containing varying concentrations of either suspending agent indicated that 3% w/v Primojel could form permanent suspensions even after 6 months storage at room temperature. The significance of these results in relation to the usefulness of these starch derivatives as suspending agents is discussed.
Effects of the vasodilator endralazine given with the antihypertensive agent guanfacine on heart rate and blood pressure of spontaneously hypertensive rats and normotensive dogs
Authors: Salzmann R , Pally W Gerber Ch , Scholtysik G 
Published: April 2011

Abstract
Endralazine (BQ 22–708, Miretilan) and guanfacine (BS 100–141, Estulic) were tested alone and in combination for their effects on blood pressure and heart rate in conscious spontaneously hypertensive rats and conscious normotensive dogs. During combined administration of endralazine and guanfacine to spontaneously hypertensive rats, guanfacine 1 mg kg−1 i.v. blocked the tachycardia caused by endralazine, 1 mg kg−1 i.v. After oral administration, the tachycardia induced by 0·5 and 1 mg kg−1 of endralazine was inhibited dose-dependently by 0·05, 0·1 and 0·5 mg kg−1 of guanfacine. The antihypertensive efficacy of endralazine was either unchanged or increased by guanfacine at 0·05-1 mg kg−1. In normotensive conscious dogs, 0·2 mg kg−1 i.v. of guanfacine antagonised the tachycardia elicited by 0·3 mg kg−1 i.v. of endralazine. The elimination of the endralazine-induced reflex tachycardia by guanfacine suggests that the combination of both drugs could be useful in antihypertensive therapy.
Temperature dependence of ethanol lethality in mice
Authors: Malcolm Richard D , Alkana Ronald L 
Published: April 2011

Abstract
The present study provides systematic evidence indicating a direct relationship between environmental temperature, rectal temperature and ethanol lethality. Male, C57 BL/6J mice, previously housed at room temperature (23 ± 1 °C), were injected intraperitoneally with 4·8 to 9·2 g kg−1 ethanol and then exposed for 24 h to ambient temperatures that did not appreciably exceed the thermally neutral range for sober mice (20 to 35 °C). There was a direct relationship between temperature and ethanol lethality at 8 and 24 h after injection. The 8 h LD50 increased by 64%, from 5·3 to 8·7 g kg−1, as environmental temperature decreased from 35 to 20 °C. The 24 h LD50 increased by 51%, from 5·3 to 8·0 g kg−1, across this temperature range. Each 5 °C reduction in ambient temperature induced a significant decrease in the rectal temperature of ethanol-injected mice. Mean rectal temperature ranged from 2·2 °C above baseline at an ambient temperature of 35 to 15 °C below baseline in the 20 °C environment. Ethanol induced a significant dose-related hypothermia in mice exposed to the 20, 25 and 30 °C environments but did not produce hypothermia in animals kept in the 35 °C environment. These findings indicate that the potency of potentially lethal ethanol doses varies with body temperature in accordance with partition and membrane expansion-fluidization theories of anaesthesia.
Absorption and excretion of isosorbide dinitrate and isosorbide-2-mononitrate in dogs
Authors: Cayen Mitchell N , Hicks David , Karounis Joanne , Dvornik Dushan 
Published: April 2011

Abstract
In a crossover design, four male dogs were given orally or i.v. [14C]isosorbide dinitrate (ISDN) or [14C]isosorbide-2-mononitrate (2-ISMN) at a dose of 1 mg kg−1 (70–80 μCi). Virtually all of the oral dose was absorbed and all of the radioactivity was excreted in the urine. The profile of serum radioactivity was similar after all drug administrations. ISDN was rapidly denitrated, giving rise to isosorbide-5-mononitrate (5-ISMN) as a major metabolite, and 2-ISMN as a minor metabolite. The apparent elimination half-life from serum of 2-ISMN and 5-ISMN was 2–3 h. More than 50% of the serum radioactivity after [14C]2-ISMN was due to unchanged drug. The apparent volume of distribution of 2-ISMN averaged 8·3 litres. The results show that, in contrast to ISDN, administration of 2-ISMN resulted in relatively high unchanged drug levels in the serum; the disposition of radioactivity after [14C]ISMN was however similar to that after [14C]ISDN. The findings support the concept that the concentrations of ISDN, 2-ISMN and 5-ISMN in the blood are inversely related to the rates of denitration, and that the vascular activity of the nitrates of isosorbide relates to the rates of their dinitration.
An evaluation of the properties of enteric coating polymers: measurement of glass transition temperature
Authors: Porter S C , Ridgway K 
Published: April 2011

Abstract
When submitted to X-ray crystallography, two enteric coating polymers, cellulose acetate phthalate and polyvinyl acetate phthalate, were found to be essentially amorphous in structure. Values for the glass transition temperature, Tg, of each polymer have been obtained using both a surface microindentation technique and differential scanning calorimetry. The effect on this parameter of an increasing concentration of a plasticizer, diethyl phthalate, has also been determined. Measured values for Tg have been compared with predicted values obtained using a suitable mixture-rule model: the surface microindentation technique values were closer to the predicted.
The influence of pH of dissolution fluid and particle size of drug on the in-vitro release of drug from hard gelatin capsules
Authors: Muhammad N A H , Newton J M 
Published: April 2011

Abstract
The influence of pH of the dissolution fluid on the in-vitro release of acetylsalicylic acid from hard gelatin capsules has been studied for a series of particle size fractions of the drug. Generally, the time required for 50% of the drug content of the capsule to appear in solution during a dissolution test, T50, increased as the pH increased from 1·2 to 2·0; thereafter the value of T50 decreased as the pH increased from 3 to 7. These changes were found to be related to the apparent solubility of the drug. The extent of the changes was found to be further dependent on the particle size of the drug. For capsules filled with particle size fractions of 2·5 and 5·5 μm median diameter, the changes were small. Larger changes were observed with particles of median diameters of 45,100, 220 and 330 μm while the largest changes (greater than two-fold) were obtained with particles of median diameter 130 and 430 μm. The type of kinetics that could be used to express the release rates was found to be particle size-dependent. For particles of 45 μm and larger, the release rate followed an apparent zero order process while an apparent first order process represented the release for the two smallest particle size fractions.
Enthalpies of solution of a series of m-alkoxy phenols in water, n-octanol and water-n-octanol mutually saturated: derivation of the thermodynamic parameters for solute transfer between these solvents
Authors: Beezer Anthony E , Hunter William H , Storey David E 
Published: April 2011

Abstract
Enthalpies of solution in both water and n-octanol have been determined for a series of phenols, in a microcalorimeter modified for titration. The thermodynamic data for solution in n-octanol and in water, as well as for transfer between the two, have been calculated from the free energies of transfer, based upon partition coefficients, and the free energies of solution, based upon solubility data. The results are discussed in terms of solute-solvent interactions in both phases and are used to assess, critically, the use of n-octanol as lipid-like solvent in QSAR studies.
Comparative plasma pharmacokinetics of theophylline and ethylenediamine after the administration of aminophylline to man
Authors: Cotgreave Ian A , Caldwell John 
Published: April 2011

Abstract
Plasma concentrations of theophylline and ethylenediamine have been examined after the oral and intravenous administration of aminophylline to three healthy male volunteers who received on separate occasions 250 mg aminophylline i.v. or 300 mg aminophylline by mouth. Blood samples were taken at regular intervals and the plasma levels of theophylline and ethylenediamine were assayed by h.p.l.c. After i.v. injection, plasma concentrations of theophylline were described by a two-compartment open model, with t1/2α 6 min, Vc 191 ml kg−1, t1/2β 6·0 h and Vp 217 ml kg−1. The plasma concentrations of ethylenediamine also exhibited a biphasic decline, the parameters of the two-compartment open model being t1/2α 7 min, Vc 214 ml kg−1, t1/2β 32 min and Vp 133 ml kg−1 (all values given are means of three subjects). The ratio of theophylline/ethylenediamine in plasma rose rapidly from the initial value of 6·2 (the ratio of the two compounds in aminophylline) over the first 10 min post injection to 47 at 120 min. After this time, ethylenediamine was not measurable in plasma, although theophylline was present for at least 6 h after dosing. Upon oral administration of aminophylline, plasma concentrations of theophylline rose to a peak value of 7·4 μg ml−1 at 1 h, falling thereafter with a t1/2 of 8·0 h. Ethylenediamine, by contrast, could only be detected over the first 2 h after dosing, in amounts below 0·4 μg ml−1. Comparison of oral and i.v. data showed the bioavailability of ethylenediamine was approximately 34% in comparison with a value of 88% for theophylline. These data indicate that the two components of aminophylline are handled independently by the body and that there is no molecular association between theophylline and ethylenediamine in biological media.
The effects of salicylate on enzymes of vitamin K metabolism
Authors: Hildebrandt E F , Suttie J W 
Published: April 2011

Abstract
The mechanism of salicylate-induced hypoprothrombinaemia has been investigated in the rat. Salicylate administration produced an increase in the percentage of the total liver vitamin that was present as vitamin K 2,3-epoxide, but the addition of salicylate did not influence vitamin K epoxide reductase activity in-vitro. Neither did it influence vitamin K-dependent carboxylase or vitamin K epoxidase activity. Both cytosolic and microsomal DT-diaphorase activities were, however, inhibited about 50% by 75 μM sodium salicylate. Salicylate inhibition was also observed when vitamin K quinone and NADH or dithiothreitol were used to support carboxylation. To achieve 50% inhibition required 0·5 mM salicylate with NADH as a reductant and 4 mM salicylate when dithiothreitol was the reductant. These results suggest that the main effect of salicylate on vitamin K metabolism is to inhibit quinone reductases and may be useful in explaining the inhibition of the biosynthesis of vitamin K-dependent clotting factors that occurs in salicylate-induced hypothrombinaemia. These data also demonstrate that the percentage of total liver vitamin present as vitamin K epoxide can be increased by agents that do not have a direct effect on the vitamin K epoxide reductase in-vitro.
The efficacy of bispyridinium derivatives in the treatment of organophosphonate poisoning in the guinea-pig
Authors: Inns Robert H , Leadbeater Levence 
Published: April 2011

Abstract
The efficacy of a number of bispyridinium compounds, including both oxime and non-oxime derivatives, has been determined against poisoning by sarin, soman, tabun and VX in guinea-pigs receiving various supporting treatments. In conjunction with atropine therapy only, the oximes were effective against sarin and VX poisoning and of them only the 4-substituted oximes were beneficial against tabun poisoning. None of the compounds was effective against poisoning by soman. When the supporting drug treatment consisted of pyridostigmine pretreatment and therapy with atropine and diazepam (this treatment itself gave considerable protection against organophosphate poisoning) both the non-oxime and oxime derivatives increased the protection against all four agents although obidoxime and TMB-4 were not beneficial against soman poisoning. The results are discussed in relation to published studies in which these compounds have been found to be beneficial against soman poisoning in atropine-treated rats and mice. It is suggested that the guinea-pig is a better model for predicting the efficacy of treatments for organophosphate poisoning in primate species.
Neurotropic effects of the optical isomers of the selective adenosine cyclic 3′,5′-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo
Authors: Wachtel Helmut 
Published: April 2011

Abstract
The efficacy of the selective adenosine cyclic 3′,5′-monophosphate (cAMP) phosphodiesterase (PDE) inhibitor (±)-rolipram and its optical isomers (0·006 to 25 mg kg−1) in inducing characteristic behavioural changes like hypothermia, hypoactivity, forepaw shaking, grooming and head twitches in rats has been examined. (+)-Rolipram was found some 15 times less potent than the racemate suggesting a stereoselective interaction with a rat brain cAMP phosphodiesterase isoenzyme. Following their intracerebral administration, the stereoisomers also demonstrated their unusual potency ratio. These findings suggested that (+)-rolipram is a less potent neurotropic PDE inhibitor in-vivo than its (-)-enantiomer.