bluuebunny/crossref_metadata_2025_split huggingface dataset:
The identification and analysis of mexiletine and its metabolic products in man
Authors: Beckett A H , Chidomere E C 
Published: April 2011

Abstract
Sensitive and specific gas-liquid chromatographic methods were developed for the analysis of mexiletine and its metabolites in urine of man. The identity of the g.l.c. peaks was established by mass-spectrometry. The hydroxylamine (Va) was qualitatively identified and determined quantitatively after conversion to the more stable oxime (Vb). Selective extraction procedures, t.l.c. and derivatization with hexamethyldisilazane (HMDS) and trifluoroacetic anhydride (TFA) were used in the qualitative identification of the major metabolites (VI-IX), particularly in distinguishing the basic products VI and VII from their corresponding alcoholic products VIII and IX. The limit of detection of the g.l.c. method was 6 to 12 ng ml-1 for compounds I-IV, and 40 to 50 ng ml-1 for compounds Vb-IX.
The effect of temperature on the tensile strength and disintegration of paracetamol and oxytetracycline tablets
Authors: Pilpel N , Esezobo S 
Published: April 2011

Abstract
The tensile strengths and disintegration times of paracetamol and oxytetracycline tablets at room temperature are higher when they have been prepared at high temperatures, e.g. 85°, than at room temperature or below, e.g. —20°. The activation energies of the two materials, 3 and 1 k cal mol−1 (13 and 4 kJmol−1) respectively, were derived from plots of log tensile strength and log disintegration time versus the reciprocal of the absolute temperature. The results have been explained in terms of sintering theory and the formation of welded bonds between particles.
The release of plasticizer from polyvinyl chloride haemodialysis tubing
Authors: Fayz S , Herbert R , Martin A M 
Published: April 2011

Abstract
The extent of migration of plasticizer from haemodialysis lines into saline and plasma has been examined and a number of different types of tubing have been compared. A model system designed to simulate in vivo haemodialysis was evolved. The method uses a continuous cyclohexane extraction in order to mimic uptake of plasticizer by body tissues. Although not an ideal system, the results obtained are indicative of the extent to which the plasticizers are leached.
Biochemical differentiation of amphetamine vs methylphenidate and nomifensine in rats
Authors: Braestrup C 
Published: April 2011

Abstract
Amphetamine-like stimulants were divided into two groups, one in which the stereotyped behaviour was not antagonized by reserpine [(+)-amphetamine, (-)-amphetamine, methamphetamine, phenmetrazine and phenethylamine] and another group in which the behavioural effects were blocked by reserpine (methylphenidate, nomifensine, pipradrol and amfonelic acid (NCA; Win 25978)). Both groups increased homovanillic acid (HVA) in whole brain 2 h after administration. The ‘methylphenidate group’ also increased brain 3,4-dihydroxy-phenylacetic acid (DOPAC) in naive rats; whereas the ‘(+)-amphetamine group’ decreased DOPAC in naive rats, as well as in reserpinized rats, α-methyl-p-tyrosine-treated rats, and after acute hemisection. The reserpine antagonism of the ‘methylphenidate group’-induced stereotyped behaviour was partially reversed by type A monoamine oxidase inhibition. The ‘(+)-amphetamine group’-induced stereotyped behaviour was not blocked by short time pretreatment with α-methyltyrosine, only by longer pretreatment intervals. The mechanisms by which the two groups are differentiated biochemically is discussed with special attention to possible intra-neuronal inhibition of dopamine oxidation by the ‘(+)-amphetamine group’.
Neurochemical correlates of ethanol withdrawal: alterations in serotoninergic function
Authors: Tabakoff Boris , Hoffman Paula , Moses Frances 
Published: April 2011

Abstract
Cessation of chronic ethanol administration, and elimination of ethanol from the body, results in a withdrawal syndrome in mice characterized by behavioural symptoms and hypothermia. During withdrawal, the accumulation rate of [14C] 5-hydroxytryptamine (5-HT) from [14C]tryptophan, was significantly lower in the brainstem of the ethanol-withdrawn animals than in controls. A similar pattern was seen in forebrain. When the rate of 5-HT accumulation was determined using pargyline, no differences occurred between control and ethanol-treated animals. The endogenous concentrations of tryptophan in plasma, and tryptophan, 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in brain were the same in ethanol-treated and control animals. It is suggested that the changes in accumulation of 14C-5-HT and 14C-5-HIAA in ethanol-withdrawn animals reflected alterations in electrical activity of serotoninergic neurons during withdrawal.
Neutral in vivo metabolites of cannabinol isolated from rat faeces
Authors: Yisak Wolde-Ab , Marianne  , Widman  , Lindgren Jan-Erik , Agurell Stig 
Published: April 2011

Abstract
The in vivo transformation of cannabinol (CBN) in the rat has been studied. Unchanged CBN and nine neutral mono-oxygenated and dioxygenated CBN metabolites have been identified. In the mono-oxygenated series the metabolites occurred in decreasing order of prominence as follows: 7-hydroxy-CBN, 4“-hydroxy-CBN, 1”-hydroxy-CBN, 2“-hydroxy-CBN, 3”-hydroxy-CBN, 5“-hydroxy-CBN and CBN-7-al. In the dihydroxylated metabolite series only 1”,7-dihydroxy-CBN and 4“,7-dihydroxy-CBN were found with the former as the more prominent metabolite.
Influence of pyridylisatogen tosylate on contractions produced by ATP and by purinergic stimulation in the terminal ileum of the guinea-pig
Authors: KaẐIĆ T , MilosavljeviĆ D 
Published: April 2011

Abstract
2-2′Pyridylisatogen tosylate (PIT), which antagonizes the inhibitory action of ATP in the taenia caeci, did not antagonize the excitatory effects of exogenous ATP and of purinergic stimulation of the terminal guinea-pig ileum. PIT (0·5–2·5 μm) potentiated the ATP-induced contractions and also the contractions produced by potassium chloride, though the potentiation could not be related to the dose in every experiment. The responses to noradrenaline, adrenaline and histamine were slightly inhibited. PIT also potentiated the contractions produced by electrical stimulation of intramural purinergic nerves when either an alternate or uniform stimulation pattern was used. The present results in which the preparation is contracted by ATP are opposite to those obtained with PIT on the taenia caeci, which is relaxed by ATP. This raises a question of duality or plurality of receptors for ATP.
A sex difference in the interaction between promethazine and morphine in the mouse
Authors: Shater H A O , Pleuvry Barbara J 
Published: April 2011

Abstract
The effects of promethazine on the antinociceptive and respiratory actions of morphine have been examined in the mouse. Moderate doses of promethazine (5 and 10 mg kg−1) potentiated morphine's action in male mice but inhibited it in female mice. Gonadectomy abolished the interaction between promethazine and morphine in both sexes, although the intensity and duration of morphine's activity was greatly enhanced in these mice. Replacement of oestradiol in ovariectomized mice restored morphine's activity to intact female control values. However, interactions between promethazine and morphine required progesterone, as well as oestradiol, replacement to obtain results approaching those obtained in intact female mice.
The influence of adrenalectomy on monoamine oxidase and NADH cytochrome c reductase in the rat heart
Authors: Corte Laura Della , Callingham B A 
Published: April 2011

Abstract
The effect of adrenalectomy on the activities of monoamine oxidase (MAO), NADH cytochrome c reductase (NCR), succinate dehydrogenase, malate dehydrogenase, fumarase, NAD+ nucleosidase and acid phosphatase in homogenates of rat hearts was examined. Besides MAO only the NCR activity increased. However, both the total and the rotenone-insensitive NCR activities increased, with that of the rotenone-insensitive being about half of the total, which indicated that the effect of adrenalectomy was exerted on components of this enzyme localized on both the inner and outer membranes of the mitochondrion. The lack of effect on the other enzymes suggests that adrenalectomy has a relatively selective action on MAO and NCR, and does not work by a generalized increase in protein synthesis or by an effect on the FAD cofactor. The MAO increase was seen with a variety of substrates, and was due to a rise in Vmax without change in Km. The response to adrenalectomy in the summer differed from that seen in the winter. The possible reasons for these effects of adrenalectomy are discussed.
Particle slippage and rearrangement during compression of pharmaceutical powders
Authors: York P 
Published: April 2011

Abstract
Compression data from different size fractions of lactose, chloroquine diphosphate, stearic acid and calcium carbonate have been analysed using the Walker and the Heckel compression equations. Points of inflection in graphs of log applied pressure vs the reciprocal of the packing fraction at low pressures corresponded closely to figures for theoretical packing conditions for equisized spheres and are attributed to a change in the stage of compression. The degree of particle slippage and rearrangement taking place during compression has been shown to increase as the particle size of the powder decreases and to be more extensive for powders composed of non-spherical particles. In addition, three types of compression behaviour have been distinguished for the four powders studied.
A model for short term drug absorption studies; comparison of sulphadiazine tablets
Authors: Saunders L , Ahmed M , Enever R P , Natunen T 
Published: April 2011

Abstract
The four parameter equation, applicable to drug absorption kinetics over a limited time period, has been used to interpret plasma concentration, time results following oral dosage with three different formulations of sulphadiazine tablets, to each of five subjects. Assessment parameters for the formulations, the time for ten percent absorption, the time interval between 10–90% absorption and the plasma concentration with no disposition (relative availability) have been estimated. Intersubject variation obscured many of the differences between formulations. To blank off this variation, plasma concentrations at each time were averaged and then random variation corresponding to the error of the assay method was applied so as to generate a number of sets of data which including the mean concentrations was equal to the number of sets in the original measurements. Kinetic analysis of these sets indicated a number of significant differences between the formulations.
Delay of castor oil diarrhoea in rats: a new way to evaluate inhibitors of prostaglandin biosynthesis
Authors: Awouters F , Niemegeers C J E , Lenaerts F M , Janssen P A J 
Published: April 2011

Abstract
Forty-four non-steroidal anti-inflammatory compounds were tested for possible effects on castor oil-induced diarrhoea in rats. A small but significant delay of intestinal evacuations was found with all compounds. Quantitatively, the oral doses required to delay diarrhoea beyond the first hour after castor oil challenge reflected the acute anti-inflammatory potency of the tested compounds. Qualitatively, the evolution of the effective doses with increasing delay was linear for potent inhibitors of prostaglandin biosynthesis. The evolution for less potent compounds was markedly different and suggested the earlier occurrence of nonspecific drug effects. Suprofen, the most potent of the series of compounds, produced the 1 h delay at an oral dose of 1·11 mg kg−1; the ED50 increased linearly to 115 mg kg−1 for a 4 h delay. Compared with other compounds the activity pattern of suprofen was consistent with that of a very potent, short-acting inhibitor of prostaglandin biosynthesis, which maintains its specific action over a wide dose range. It is concluded that delay of castor oil-induced diarrhoea in rats allows a detailed characterization of aspirin-like compounds, and that inhibition of prostaglandin biosynthesis is insufficient to suppress the intestinal effects of the oil.
Dopamine-β-hydroxylase release following acute selective sympathetic nerve stimulation of the heart, spleen and mesentery
Authors: Algate D R , Leach G D H 
Published: April 2011

Abstract
An increase in the concentration of dopamine-β-hydroxylase (DBH) in the blood perfusates of the heart, spleen and mesentery of pithed rats was detected following selective sympathetic nerve stimulation. Furthermore, the concentration of enzyme released by each organ correlated with the stimulation frequency. The results provide further corroborative evidence that the concentration of DBH in the plasma is related to the degree of sympathetic tone. If the sampling methods described were applied to non-spinalized animals, the concentrations of DBH in organ perfusates could be used as an index of sympathetic nervous tone and thus provide a useful preparation for the study of drugs on the sympathetic nervous system.
Isolation and identification of the fluorescent degradation product of some β-lactam antibiotics
Authors: Barbhaiya R H , Brown R C , Payling D W , Turner P 
Published: April 2011

Abstract
A fluorescent degradation product of cephalexin, recently employed in the determination of this antibiotic in aqueous solution and human plasma, has been isolated and identified as 2-hydroxy-3-phenyl-6-methylpyrazine. Spectroscopically and chromatographically the product is indistinguishable from that obtained by the same method from a series of other cephalosporins and penicillins bearing an α-amino group on the side-chain, and from the pyrazine structure produced by synthesis. Two reported methods for the fluorimetric determination of ampicillin have also been found to yield the same degradation product and not the suggested diketopiperazine structure.
Fate of [14C]warfarin in guinea-pigs: effect of a concomitant single dose of salicylate
Authors: Wong L T , Solomonraj G , Thomas B H 
Published: April 2011

Abstract
When a single dose of sodium salicylate (177·8 mg kg−1, by mouth) was given with [14C] warfarin (1 mg kg−1, i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14C for 6 h. At 1 h, salicylate increased the distribution of 14C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14C in the first 5 h after salicylate and a decrease in 14C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [14C]warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin.
Rectal absorption of homatropine [14C]methylbromide in the rat
Authors: Cramer M B , Cates L A , Clarke D E 
Published: April 2011

Abstract
Homatropine[14C]methylbromide (HMB-14C) was administered to rats by intramuscular injection, oral gavage and rectal suppository. Plasma concentrations of 14C were measured over the subsequent 12 h. Peak plasma concentrations were higher and achieved more rapidly after rectal administration than by the other routes whether HMB-14C was administered in a water-soluble suppository base or in aqueous solution. Twelve h after the suppositories were inserted and retained 28% of the 14C had been excreted in the urine while 56% remained in the large intestine. Unlabelled HMB, given in rectal suppositories to anaesthetized rats, caused prompt blockade of the effects of vagal stimulation on pulse rate and of intravenous acetylcholine on blood pressure. These results confirm the rapid rectal absorption of the drug.
The determination of sulphoxide in degraded phenothiazine formulations by difference spectrophotometry
Authors: Davidson A G 
Published: April 2011

Abstract
A method is described for the assay of phenothiazine sulphoxides which may be formed in phenothiazine formulations during storage under unfavourable conditions. The assay is based upon the measurement of difference absorbance of the sulphoxide solution in 0·2 m hydrochloric acid relative to an equimolar solution reduced with zinc dust. A solvent extraction procedure avoids interference from colouring agents and coloured photolytic breakdown products of the phenothiazines. The assay is specific in the presence of intact drug, sulphone and co-formulated drugs for the formulations examined and is sensitive to 0·5% of the total phenothiazine present as sulphoxide. Many aqueous formulations stored in partially filled containers have been shown to contain up to 31·5% of the total phenothiazine as sulphoxide.
The percutaneous absorption of phenolic compounds: the mechanism of diffusion across the stratum corneum
Authors: Roberts M S , Anderson R A , Swarbrick J , Moore D E 
Published: April 2011

Abstract
The effect of temperature on the permeation of phenolic compounds from aqueous solution through excised human skin has been examined. From a thermodynamic analysis of the data, a mechanism is postulated by which these solutes penetrate through human skin. For the more polar solutes it is suggested that the main resistance to penetration is the lipid barriers in the stratum corneum. Diffusion of these substances through the stratum corneum appears to depend on the breaking of hydrogen bonds in the desolvation of the solute during this penetration process and by the overall ‘viscosity’ of the stratum corneum. With non-polar solutes, the aqueous boundary layers appear to provide an additional barrier to the penetration of phenolic compounds.
Baclofen (β-p-chlorophenyl-γ-aminobutyric acid) enhances [3H]γ-aminobutyric acid (3H-GABA) release from rat globus pallidus in vitro
Authors: Kerwin R , Pycock C 
Published: April 2011

Abstract
The rat globus pallidus has been investigated as a possible model in which to study pre-synaptic G AB A mechanisms in vitro. (±)-Baclofen (300 μM-1 mM) significantly enhanced the release of radioactivity from superfused slices of rat globus pallidus prelabelled with 3H-GABA in vitro. This releasing action was specific to the (+)-isomer of baclofen: neither the (—)-isomer nor another neuronal depressant DL-α-∞-diaminopimelic acid had any significant effect. The releasing effect of baclofen appeared unrelated to the phenethylamine moiety of its structure as neither β–phenethylamine nor dopamine evoked release of 3H-GABA from pallidal slices. Baclofen increased the efflux of radioactivity from pallidal slices prelabelled with either [3H]β-alanine or [3H]diaminobutyric acid in vitro. The use of specific glial and neuronal GABA uptake blocking compounds (β-alanine and (±)-cis-1,3-amino-cyclohexanecarboxylic acid) did not permit resolution of the elements from which baclofen was evoking [3H]GABA release. Baclofen also inhibited uptake of [3H]GABA into pallidal slices with an IC50 value of 6 × 10−4 M. The GABA-like properties of baclofen may be related to the (+)-isomer while non-specific neuronal depressant actions are an effect of the (—)-isomer. The potential of the (+)-isomer as an antipsychotic agent while (—)-baclofen remains the effective antispastic drug free from unwanted side-effects, is discussed.
Differences in responsiveness to adipokinetic agents between white epididymal and brown interscapula adipose tissue from rats
Authors: Itaya Koichi 
Published: April 2011

Abstract
Lipolytic activity was studied in brown and white adipose tissue of rats in vitro. 5-Hydroxytryptamine (5-HT), phenylephrine, noradrenaline, adrenaline and isoprenaline were used as adipokinetic agents. All stimulated lipolysis in brown adipose tissue, but 5-HT and phenylephrine did not in white adipose tissue. A β-blocking drug, propranolol, inhibited the stimulatory effect of the agents in both adipose tissues. However, an α-blocking drug, phentolamine, further increased the lipolysis induced by noradrenaline or adrenaline in brown adipose tissue and inhibited the effect of isoprenaline. In white adipose tissue, its action was to marginally decrease the effect of adrenaline and noradrenaline. Increase in the pH of the incubation medium stimulated FFA and glycerol release in brown adipose tissue, but not in the epididymal adipose tissue. This effect of pH on lipolysis was further enhanced by phentolamine and decreased by propranolol. Increase of lipolysis with pH was not seen with brown fat tissue from the reserpine-treated rats. These results show that brown adipose tissue of the rat has an α-receptor with inhibitory effects on lipolysis that is affected by α- or mixed-type adrenergic agonists, noradrenaline and adrenaline.
The effect of PGE1 on peristalsis and on perivascular nerve inhibition of peristaltic activity in guinea-pig isolated ileum
Authors: Sanger G J , Watt A J 
Published: April 2011

Abstract
The effect of PGE1 on peristalsis of guinea-pig isolated ileum was examined using a modified Trendelenburg method to evoke and record peristaltic activity. PGE1 (14 nm, 0·11 μm and 0·56 μm) increased peristaltic activity of both longitudinal and circular muscle, mainly by increasing the amplitude of contraction. Preparations of ileum subjected to a ‘minimal’ peristaltic stimulus were more sensitive to the effects of PGE, than were preparations subjected to a ‘just-maximal’ peristaltic stimulus. The inhibition of peristaltic activity caused by perivascular nerve stimulation was antagonized by 0·56 μm PGE1 but slightly increased by 14 nm PGE1.
Percutaneous absorption: theoretical description
Authors: Albery W John , Hadgraft Jonathan 
Published: April 2011

Abstract
Equations are derived to describe the percutaneous absorption of a substance through the epidermal barrier. The treatment includes interfacial barriers and allows for the depletion of the substance in the external phase. The equations are derived both for the continuous application and for pulse experiments where the drug is applied for a time, then removed, and the response occurs some time after the removal of the drug. Competition between the drug diffusing through the keratinized cells (transcellular route) and diffusing in the interstitial channels around the cells (intercellular route) is also considered.
Depletion of brain noradrenaline, but not dopamine, by intracerebral 6-hydroxydopamine potentiates convulsions induced by electroshock
Authors: Mason Stephen T , Corcoran Michael E 
Published: April 2011

Abstract
Intracerebral injection in rats of 4 μg of the catecholamine neurotoxin 6-hydroxydopamine was used to deplete forebrain noradrenaline to less than 10% of control values and separately to deplete brain dopamine to less than 15% of control. The susceptibility of these animals to electroconvulsive shock-induced convulsions was examined, and a significant potentiation of the response was seen in the rats depleted of noradrenaline but not in those depleted of dopamine. The duration of the convulsion was significantly increased as a result of loss of forebrain noradrenaline.