bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutual suppression of cardiovascular effects of some β-adrenoreceptor agonists in the cat
Authors: Atkinson Judith M , Rand M J
Published: April 2011

Observations were made of the effects of adrenaline, isoprenaline and orciprenaline on the blood pressure, heart rate and configuration of the ECG in cats. The effects of single injections of these amines in producing a rise in heart rate and a fall in blood pressure were reduced during the intravenous infusion of any one of them: the pressor response to injected adrenaline was enhanced during an infusion. Combinations of these amines did not produce changes in the configuration of the ECG. These experiments were motivated by allegations of acute toxic effects on the cardiovascular system of large doses, or of combinations, of sympathomimetic bronchodilators in asthma. No evidence of deleterious effects of interactions was obtained.
The optical rotatory dispersion of some N-decyl-N-N-dimethylalanine salts and their critical micelle concentrations
Authors: Bonkoski S , Perrin J H
Published: April 2011

The optically active salts of N-decyl-NN-dimethylalanine are shown to have anomalous optical rotatory dispersion curves and to not be fully ionized in aqueous solution. The position of the peak in the 225 to 230 mμ region varies with concentration of the surfactant as does the molecular rotation at a given wavelength. The positions of the peaks and the molecular rotations at these low wavelengths are pH sensitive. The change in molecular rotation with concentration enables the critical micelle concentrations of L and D N-decyl-NN-dimethylalanine hydrobromides to be determined by optical rotatory dispersion measurements, the results agreeing well with the values calculated from the literature. The change in rotation on micelle formation appears to be due to a change in the degree of ionization of these weak acids, a fact which is confirmed by pH measurements on these solutions.
The polymorphism of phenobarbitone
Authors: Mesley R J , Clements R L , Flaherty B , Goodhead K
Published: April 2011

The polymorphism of phenobarbitone has been investigated using infrared spectroscopy, X-ray diffraction and differential scanning calorimetry. Eight crystalline modifications have been isolated and shown to have distinguishable infrared absorption spectra and X-ray powder diffraction patterns. Other forms were found to be present in mixed crystals and molecular compounds obtained from mixtures of phenobarbitone with other barbiturates. Differential thermograms of three forms of thialbarbitone are also given.
The depletion and recovery of noradrenaline in the brain and some sympathetically innervated mammalian tissues after tetrabenazine
Authors: Häggendal Jan
Published: April 2011

The depleting effect of tetrabenazine on the monoamine levels appears generally to be less in peripheral tissues than in the central nervous system. The noradrenaline levels in brain and some sympathetically innervated tissues such as heart, submandibular glands, and skeletal muscle were examined in the rat after administration of the drug. The levels of 5-hydroxytryptamine, dopamine and noradrenaline were also estimated in the rabbit brain after tetrabenazine and compared with the levels in the rabbit heart. In both the brain and peripheral tissues the monoamine levels were strongly reduced 4 hr after tetrabenazine and increased thereafter, reaching normal levels after about 36 to 48 hr. The site of action of tetrabenazine is briefly discussed and compared to the site of action of reserpine.
Relaxation of the guinea-pig tracheal chain preparation by N6, 2‘-O-dibutyryl 3’,5‘-cyclic adenosine monophosphate
Authors: Moore P F , Iorio L C , McManus J M
Published: April 2011

N 6,2′-O-Dibutyryl 3′,5′-cyclic adenosine monophosphate (dibutyryl 3′,5′-amp), isoprenaline and theophylline relax the guinea-pig tracheal chain preparation; whereas 3′,5′-cyclic adenosine monophosphate (3′,5′-amp) does not. The relaxant effect of isoprenaline, but not that of dibutyryl 3′,5′-amp, was blocked by propranolol. 3′,5′-amp is hydrolyzed rapidly by beef heart phosphodiesterase whereas dibutyryl 3′,5′-amp is not. The presence of equimolar concentrations of dibutyryl 3′,5′-amp does not alter the rate of phosphodiesterase mediated hydrolysis of 3′,5′-amp. These data are consistent with the theories that relaxation of the guinea-pig trachea may be mediated by 3′,5′-amp and that dibutyryl 3′,5′-amp acts by mimicking 3′,5′-amp at its site of action.
Blocking action of tetrahydrocannabinol upon transmission in the trigeminal system of the cat
Authors: Lapa A J , Sampaio C A M , Timo-Iaria C , Valle J R
Published: April 2011

The influence of tetrahydrocannabinol upon polysynaptic reflexes involving the trigeminal system was investigated in cats by recording potentials from either the superior sensory nucleus of the trigeminal nerve or the nerve itself where it enters the pons. Stimulation of the lower eye-lid just sufficient to evoke a mild contraction of the orbicularis muscle was employed. Amplitude of the postsynaptic potentials began to decrease 5 to 10 min after injection of 0·8 or 1·0 mg/kg in most experiments. The presynaptic potential also underwent a striking depression whereas the tibialis nerve potentials, used as control, were practically unaffected. It seems that impairment of the impulse conduction along the presynaptic fibres instead of a central synaptic blockade was the dominant effect of thc. However, a blockade of synaptic transmission is likely to occur in other centres accounting for other neural effects of thc.
A note on the effects of some cholinergic and anticholinergic drugs on the aggressive behaviour and spontaneous electrical activity of the central nervous system in the ant, Formica rufa
Authors: Kostowski Wojciech
Published: April 2011

The influence of various cholinergic and anticholinergic drugs on the aggressive behaviour and electroencephalogram was investigated in the ant, Formica rufa. Both atropine and scopolamine decreased aggressiveness and electrical activity of the brain whilst tubocurarine caused an opposite effect. The possible role of nicotinic and muscarinic receptors in the central nervous system of the ant is discussed.
The use of the Coulter Counter for the particle size analysis of some emulsion systems
Authors: Shotton E , Davis S S
Published: April 2011

The Coulter Counter is suitable for the particle size analysis of emulsions containing insoluble oils. All the emulsions obey the log normal distribution of particle size if allowance is made for particles below the lower limits of the apparatus. The variation of particle size with emulsifier concentration and volume fraction has been studied for liquid paraffin emulsions stabilized by potassium laurate and potassium arabate.
The use of supports in the lyophilization of oil-in-water emulsions
Authors: Lladser M , Medrano C , Arancibia A
Published: April 2011

The results of drying oil-in-water emulsions by lyophilization have shown this process could be applied to emulsions having dissolved in the aqueous phase a solid material which acts as support for the oily phase after the water has been removed. The rate of creaming and the globule size distribution were also investigated. The tests were made before and immediately after lyophilization, and after 20 and 40 days of storage at room temperature (18–20°) at 0° ±1° and at 40° ±1°. The emulsions were coarser and creaming rate was increased after lyophilization.
Pharmacological studies of a new antitussive, 4-phenyl-l-piperidinecarboxamide (AH 1932)
Authors: Brittain R T , Lees Effie J , Spencer P S J
Published: April 2011

4-Phenyl-1-piperidinecarboxamide (AH 1932) markedly inhibits coughing induced in laboratory animals by chemical or mechanical irritation of the respiratory tract or by electrical stimulation of the superior laryngeal nerve. The compound is effective administered orally or parenterally and is at least as active as codeine. In contrast to codeine the antitussive activity of AH 1932 persists for 6 hr after oral administration. The evidence suggests a central site of action for AH 1932. The drug has a low acute toxicity in mice and rats, is devoid of analgesic activity, has no effect on the respiratory system and does not affect gastrointestinal propulsion. Cardiovascular effects are minimal. AH 1932 possesses weak spinal interneuron blocking activity unlikely to limit its use as a cough suppressant.
Histochemical studies on the depletion of noradrenaline by adrenaline in adrenergic nerves of the rat iris
Authors: Haining C G , Heydon Julia L , Murray L R
Published: April 2011

The intensity of fluorescence produced in adrenergic nerves by exposure to formaldehyde under controlled conditions and levels of tissue catecholamines were determined in rat irides. Incubation of irides in Krebs solution containing (-)-adrenaline (0·1–10 μg/ml) led to a temperature-dependent reduction of fluorescence intensity, a reduction in tissue noradrenaline and a gain in tissue adrenaline. The changes in fluorescence were reversed by subsequent incubation of the tissue in the presence of (-)-noradrenaline (0·1–1 μg/ml). A reduction of fluorescence intensity and tissue noradrenaline in the rat iris, followed by recovery over 16 h, was also produced by exposing the cornea to a 1 or 5% solution of (-)-adrenaline. The application of these results to studies on noradrenaline uptake in adrenergic nerves is discussed.
Gas chromatographic analysis of acetylsalicylic acid, phenacetin, caffeine, and codeine in APC and codeine tablets
Authors: Dechene Earl B , Booth L H , Caughey M J
Published: April 2011

All active ingredients in APC and codeine tablets are determined by gas chromatographic procedures after separation of acetylsalicylic and phenacetin from caffeine and codeine.
Preservation of fluorescein solutions against contamination with Pseudomonas aeruginosa
Authors: Richards R M E , Suwanprakorn P , Neawbanij S , Surasdikul N
Published: April 2011

A combination of phenylmercuric nitrate and phenylethyl alcohol was more effective in preserving fluorescein solutions against contamination with P. aeruginosa than phenylmercuric nitrate alone. P. aeruginosa cells, grown in the presence of phenylethyl alcohol and then washed were rendered sensitive to chemical inactivation.
A perfused tail artery preparation from the rat
Authors: NICHOLAS T E
Published: April 2011

The isolated perfused tail artery of the rat responds by constriction to 1·0 ng (-)-noradrenaline, and would be suitable for the assay of sympathomimetic amines. Electrical stimulation of this preparation is shown to activate solely postganglionic adrenergic nerve terminals. Tachyphyllaxis to angiotensin, vasopressin and bradykinin preclude the use of this preparation for their assay.
The influence of the monoamine oxidase inhibitor pargyline hydrochloride on the retention of dopamine in the isolated perfused spleen of the cat
Authors: Street Denise M , Roberts D J
Published: April 2011

Much of the dopamine accumulated in the cat spleen after the intravenous infusion of this amine into the anaesthetized animal appears in the venous effluent when the spleen is subsequently isolated and perfused with a dopamine-free medium. Pre-treatment of the animals with the monoamine oxidase inhibitor pargyline hydrochloride has no effect on the rate of decline of the spleen content of dopamine resulting from perfusion, but appears to significantly reduce the amount of dopamine that can be removed from the spleen in this way. The significance of these findings is discussed in relation to a “false” neurochemical transmitter hypothesis for the antihypertensive effects of pargyline.
Effects of convulsant barbiturates on vascular smooth muscle
Authors: Hupka A L , Williams The Late J K , Karler R
Published: April 2011

The convulsant barbiturate, 5-(2-cyclohexylidene-ethyl)-5-ethyl barbituric acid (cheb), produces contraction in rabbit aortic strips. Contractions effected by either cheb or tyramine were preceded by a lag time and both agents induced tachyphylaxis; however, cross-tachyphylaxis could not be demonstrated. Phenoxybenzamine and atropine failed to affect cheb-induced responses, whereas pentobarbitone selectively blocked and also reversed cheb contractions. Prevention, but not reversal, of tachyphylaxis was also accomplished with pentobarbitone. These results suggest that cheb does not act through the release of noradrenaline or acetylcholine; nor does it exert an effect on the receptors for these amines or on those for histamine. Pentobarbitone, however, appears to compete with cheb for common receptors. Another convulsant barbiturate, 5-ethyl-5-(dimethylbutyl)barbituric acid (dmbb), and its optical isomers were also examined. The racemic mixture had no contractile activity, but the (+)-isomer elicited cheb-like effects. The (-)-isomer, on the other hand, was like pentobarbitone in that it antagonized both cheb- and (+)-dmbb-induced contractions. These studies illustrate that convulsant barbiturates are able to stimulate vascular smooth muscle; therefore, it is suggested that the rabbit aortic strip may serve as an in vitro working model for study of the mechanism of action of these drugs in the central nervous system.
On the role of a central adrenergic mechanism in morphine analgesic action
Authors: Vedernikov Yu P , Afrikanov I I
Published: April 2011

The influence of drugs interfering with brain monoamine metabolism on morphine analgesia of rats was estimated by the tail pressure method. Central adrenergic stimulation produced by apomorphine, cocaine, pyrogallol or amphetamine led to stereotyped behaviour and elevation of the pain threshold. Lower doses of these drugs potentiated morphine analgesic action. Reserpine, iproniazid and disulfiram weakened morphine analgesic action. α-Methyldopa increased morphine action and (±)-tryptophan did not influence it significantly.
Solubilization and rheology of the system ascorbic acid-water-polysorbate 80: temperature effects
Authors: Nixon J R , Chawla B P S
Published: April 2011

Changes induced by temperature in the relative position and extent of the isotropic and liquid crystal phases present in the ascorbic acid-water-polysorbate 80 system have been recorded. Increases in temperature reduce the size of the liquid crystal phase. This phase is pseudoplastic, but a small central region also shows thixotropic hysteresis loops. On recycling, most systems show Newtonian behaviour. In the isotropic regions, an increase in temperature results in a fall in log of viscosity proportionate to 1/Tabs, but in the liquid crystal region an increase in temperature may cause a similar fall or, because of a change in the relative position of the system within the liquid crystal region, an increase.
A comparison of the effects on blood glucose and ketone-body levels, and of the toxicities, of pent-4-enoic acid and four simple fatty acids
Authors: Senior A E , Sherratt H S A
Published: April 2011

Some effects of the hypoglycaemic compound pent-4-enoic acid in rats and mice, are described. Pent-2-enoic acid, pentanoic acid, cyclopropanecarboxylic acid and cyclobutanecarboxylic acid, which were shown to be non-hypoglycaemic, were used as controls. Pent-4-enoic acid and cyclopropanecarboxylic acid caused ketosis in rats, with a lowering of the blood β-hydroxybutyrate/acetocetate (βHB/AcAc) ratio; some ketosis was caused by the other fatty acids but the βHB/AcAc ratio was not changed. Pent-4-enoic acid caused an increase in free fatty acid concentration in rat plasma. The acute toxicities of these compounds in mice were determined. The mechanism of the hypoglycaemic action of pent-4-enoic acid is discussed in relation to that of hypoglycin.
The preferred conformation of noradrenaline and a consideration of the α-adrenergic receptor
Authors: Kier Lemont B
Published: April 2011

The preferred conformation of noradrenaline has been calculated using extended Hückel molecular orbital theory. The conformation was found to be identical to the previously calculated conformation of (—)-ephedrine in respect to the relation of the quaternary and hydroxyl groups and the phenyl ring. These findings reinforce the previous hypothesis of the nature of the α-adrenergic receptor and also support the view that these molecules function at the receptor in their preferred conformations.
The effects of osmotic pressure on procaine-induced vacuolation in cell culture
Authors: Finnin B C , Reed B L , Ruffin N E
Published: April 2011

The effect of increased tonicity on procaine-induced vacuolation in the H.Ep.2 cell has been investigated. An increase in tonicity equivalent to about 1·3% NaCl was found to reduce the formation of the drug-induced vacuoles and also to reduce established vacuolation. There appeared to be no difference in the effectiveness of the osmotic adjusting substances used (sodium chloride, sodium sulphate, glucose, fructose and sucrose) when employed in osmotically equivalent amounts.
The corticotrophic activity of tetracosactide in the adrenal ascorbic acid depletion test
Authors: De Jager E , Van Der Vies J , Staehelin M
Published: April 2011

Using the subcutaneous adrenal ascorbic acid depletion test in hypophysectomized rats it was found that tetracosactide (synthetic 1–24 corticotrophin) could not be assayed against the International Working Standard (IWS) for natural corticotrophin because of a difference in the slopes of the dose-response curves of the preparations. Valid potency estimates were obtained when tetracosactide was assayed against a standard preparation closely similar to the 2nd International Standard for natural corticotrophin. By comparing this standard with the IWS, the best estimate of the potency of tetracosactide in terms of the IWS was 99 (92–106) units/mg. Five different batches of tetracosactide have yielded identical biological potencies. Since tetracosactide can be adequately standardized by physical and chemical-analytical criteria, labelling and dosage on a mg base instead of in units is recommended.
Metabolism and excretion of promazine by the horse
Authors: Weir J J , Sanford J
Published: April 2011

The urinary excretion of promazine and its metabolites has been examined in five horses, by ultraviolet spectrometry and thin-layer chromatography. In each horse, excretion continued for at least 96 h although the amount excreted was low, being about 11% of the dose. No correlation of excretion and pH or urinary volume was observed. Glucuronic acid conjugates predominated, their ratio to unconjugated metabolites being about 5:1. Promazine was found only in small amounts and traces of unconjugated sulphide metabolites were found in only one horse. At least nine metabolites of promazine were detected, the major one being the glucuronide of 3-hydroxypromazine.
Book Reviews
Authors: Fish Frank , Gilbert J N T
Published: April 2011

Book reviewed in this article:

POWDERED VEGETABLE DRUGS. By Betty P. Jackson and Derek W. Snowdon.

PRACTICAL PHARMACEUTICAL CHEMISTRY. Second Edition, Part I. By A. H. Beckett and J. B. Stenlake.
The pharmacology of 5-(2-t-butylamino-1-hydroxyethyl) salicylamide (AH 3474), a β-adrenoreceptor blocking agent
Authors: Blackburn C H , Byrne L J , Cullum V A , Farmer J B , Levy G P
Published: April 2011

AH 3474 is a specific β-adrenoreceptor antagonist, devoid of stimulant activity. When given by mouth to conscious guinea-pigs and dogs, AH3474 and propranolol are equiactive in antagonizing isoprenaline-induced tachycardia. In anaesthetized animals AH 3474 was 2–4 times less active than propranolol when given intravenously. A similar potency ratio was found in volunteer studies in which the drug was taken orally. On isolated tissues AH 3474 was much less active than propranolol. AH 3474 had 1/10th the activity of propranolol in blocking the inhibitory action of isoprenaline on the rat uterus and was at least 100 times less active in antagonizing the tachycardia induced by adrenaline on the guinea-pig atria. In vitro, equilibrium conditions for AH 3474 were obtained in 15 min, whereas 45 min were required for propranolol. AH 3474 antagonized the cardiac arrhythmias induced by ouabain in the anaesthetized dog. The amount required far exceeded the β-adrenoreceptor blocking dose. AH 3474 possessed no “quinidine-like” actions on cardiac muscle of dog or guinea-pig. The local anaesthetic activity of AH 3474 was 400 times less than that of propranolol.
Comparison of intracisternally and intraperitoneally injected harmaline on body temperature and tremor in the rat
Authors: Bruinvels J
Published: April 2011

Low doses of harmaline (1–10 mg/kg) injected intraperitoneally into rats caused hypothermia, while higher doses (10–30 mg/kg) induced tremor in addition to hypothermia. Harmaline injected intracisternally decreased body temperature without inducing tremor. To induce a maximal fall in body temperature following intraperitoneal injection of harmaline, 1000 times more harmaline was needed than after intracisternal administration. Harmaline by this route induced hypothermia much faster than by intraperitoneal injection. It is concluded that harmaline-induced hypothermia is at least partly localized in the central nervous system and is not associated with the tremor.
The effect of two synthetic steroids on the ultrastructure of the liver of Rattus norvegicus L.
Authors: Hines W J W
Published: April 2011

Flumedroxone acetate and an analogue [17-acetoxy-3β(β-carboxypropionyloxy)-6-trifluoromethylpregn-5-ene-20-one] each produce a liver weight increase and a change in hepatic cell ultrastructure, following chronic administration in mice and rats. In all liver cells there is much proliferation of the smooth endoplasmic reticulum, which arises from the ergastoplasm, or rough membranes. An effect on esterase enzyme specificity and the evidence for the induction of an esterase isoenzyme after treatment with these steroids, is referred to. The distribution of the new smooth endoplasmic reticulum is of interest as it varies with each analogue.
A note on the colorimetric determination of butyrophenones with 3,5-dinitrobenzoic acid
Authors: Haemers A , Van Den Bossche W
Published: April 2011

Butyrophenones react with 3,5-dinitrobenzoic acid in an alkaline medium with the formation of a red coloured complex. This reaction can be used for the quantitative determination of these drugs in pharmaceutical preparations. The influence of the ethanol concentration, the alkalinity and the reagent concentration was investigated separately. The results show that the proposed method is suitable for the assay of solutions and tablets. It requires less time than existing methods.
The in vitro and in vivo metabolism of optically active methylcyclohexanols and methylcyclohexanones
Authors: Elliott T H , Jacob E , Tao Rosaline C C
Published: April 2011

The in vitro reduction and oxidation of the isomeric methylcyclohexanones and methylcyclohexanols by horse liver alcohol dehydrogenase, in the presence of NADH2 or NAD has been studied. The enzymic reactions closely resemble the corresponding in vivo metabolic conversions and support the view that the oxido-reductase in the animal body is similar to liver alcohol dehydrogenase. The findings are discussed in terms of the conformations of the alcohols and ketones and a correlation of the observed rates, Km values, and the steric specificity supports the view that the in vivo inversion of the thermodynamically less stable alcohols (±)-cis-2-, (±)-trans-3-, and cis-4-methylcyclohexanol could occur through a ketone intermediate.
The effects of 1-[di(2-chloroethyl)aminomethyl]benzimidazole and related compounds on the growth of experimental tumours
Authors: Reddy V V Subba , Sirsi M , Revankar G R , Siddappa S
Published: April 2011

The inhibitory activity of some benzimidazole Mannich-base nitrogen mustards on the growth of experimental tumours, viz. mouse fibrosarcoma in mice and Yoshida ascites sarcoma in rats has been examined. Amongst the compounds tested 5,6-dichloro-1-[di(2-chloroethyl)aminomethyl]benzimidazole and 1-[di(2-chloroethyl)-aminomethyl]-2-phenylbenzimidazole showed inhibitory effect on mouse fibrosarcoma; while 4-bromo-1-[di(2-chloroethyl)aminomethyl]benzimidazole, 4-chloro-1-[di(2-chloroethyl)aminomethyl]-benzimidazole and 1-[di(2-chloroethyl)aminomethyl]-5-methoxybenzimidazole were active against Yoshida ascites sarcoma.
The evaluation of inflammation induced by material implanted subcutaneously in the rat
Authors: Hicks R
Published: April 2011

Inflammation induced by cotton pellets, implanted subcutaneously in the rat, has been compared with that resulting from implantation of pellets impregnated with irritant substances. Time sequences of fluid exudation and granulation tissue formation have been evaluated by differential weighing. Increased irritancy of the pellets resulted in increased exudate volume, and heavier granulation deposition. Contact between granulation tissue and irritant pellets was delayed until the volume of exudate had subsided. Penetration of the pellet was also delayed. Systemic anti-inflammatory effects from granulomata surrounding implanted pellets were related to either the size of the implantation lesion or the degree of irritancy of the implanted material. Evaluation of granulation tissue formation is suggested as a test for irritancy of surgical fabrics.
The effect of ultrasonic energy on the extraction of anthraquinones from senna pericarps
Authors: Woodford R , Morrison J C
Published: April 2011

Ultrasonic irradiation increased the extraction rate of rhein glycosides, free anthraquinones and total water-soluble solids from whole senna pericarps, irrespective of the temperature conditions employed. An increase in ultrasonic power from 35 to 100 W increased the yield of extractable constituents over a 15 min period, the ratio of rhein glycosides to total water-soluble solids being higher in extracts prepared using ultrasound than in preparations obtained by simple maceration, but that ratio decreased slightly with an increase in ultrasonic power. Ultrasonic irradiation produced occasional visible damage to epidermal cell walls and the significance of this in the extraction of senna pericarps is discussed.
The diffusion of sennoside A through a cellulose membrane
Authors: Woodford R , Morrison J C
Published: April 2011

The diffusion rate of sennoside A through a cellulose membrane into water increased irrespective of the temperature conditions under which diffusion took place, when the membrane was irradiated with ultrasound. The results are consistent with the hypothesis of boundary layer disruption at the phase interface and their significance in the effect of ultrasonic energy on the aqueous extraction of senna pericarps is discussed.
Calibration and application of high torques to a reaction air turbine viscometer
Authors: Barry B W , Saunders G M
Published: April 2011

A reaction air turbine viscometer has been calibrated with the air bearing placed both horizontally and vertically. It has been shown that changing the position of the bearing varied the result by less than 2%. The air bearing pulley employed in the calibration is described; this may also be used to apply high torques during a rheological analysis.
Quantitative analysis of 4‘-chloro-2-ethylaminopropiophenone, 4’-chloro-2-amino-propiophenone and the corresponding aminoalcohols in a mixture of the four compounds
Authors: Beckett A H , Hossie R D
Published: April 2011

A method specific for the quantitative analysis of 4′-chloro-2-ethyl-aminopropiophenone, and 4′-chloro-2-aminopropiophenone in the presence of their corresponding aminoalcohols in urine is described. The instability of the aminoketones makes extraction from alkaline solutions impractical. Hence they are quantitatively reduced to their corresponding alcohols and analysed using gas-liquid chromatography.
The relation between circulating and tissue concentrations of salicylate in the mouse in vivo
Authors: McArthur J N , Dawkins P D , Smith M J H
Published: April 2011

The blood and water contents of mouse liver, brain, kidney, heart, spleen and skeletal muscle were measured and used to correct observed values for the salicylate concentrations in these tissues after the intraperitoneal injection of the drug. The binding of salicylate in vitro to mouse whole blood, liver, kidney and brain was studied. It was concluded that blood, liver and kidney but not the other tissues, bind the drug in vivo.
The effect of acute adrenalectomy on the blood pressure responses to noradrenaline and to preganglionic nerve stimulation
Authors: Drew G M , Leach G D H
Published: April 2011

The quantitative contribution of the adrenal medulla to the pressor response resulting from stimulation of the entire preganglionic sympathetic spinal outflow of the rat, has been estimated. Adrenalectomy reduced the pressor responses not only to preganglionic nerve stimulation but also to injected noradrenaline. This reduction in cardiovascular sensitivity occurred within about 10 min of adrenalectomy and continued throughout the course of each experiment. Intramuscular injection of cortisone (20 mg/kg) restored cardiovascular sensitivity to injected noradrenaline thus allowing analysis of the adrenal medullary component of the overall response to spinal nerve stimulation.
The isolated perfused heart preparation: two suggested improvements
Authors: Beckett P R
Published: April 2011

A new method of recording the contractions of the isolated perfused heart is described. By “transverse” recording, a signal of simple waveform is obtained from the right ventricle at constant diastolic tension. Changes in heart rate and force of contraction of the rat isolated perfused heart caused by (-)-noradrenaline were measured. Of the three methods of assessing the response: (1) the increment as a percentage of the control record, (2) the increment in absolute units and (3) the increment as a percentage of the maximum, the latter has most pharmacological meaning.
The synthesis and anti-acetylcholinesterase activities of (+)-physostigmine and (+)-physovenine
Authors: Dale F J , Robinson B
Published: April 2011

(+)-Physostigmine and (+)-physovenine have been synthesized. The anti-acetylcholinesterase activities of these two bases, which have been investigated in vitro using erythrocyte acetylcholinesterase, have been found to be much lower than the corresponding activities of the alkaloids (-)-physostigmine and (-)-physovenine. Possible reasons for these activity differences are discussed.
The stabilization-lysis action of anti-inflammatory steroids on lysosomes
Authors: Lewis D A , Symons A M , Ancill R J
Published: April 2011

The effect of anti-inflammatory steroids on lysosomal enzyme release has been investigated. Most of the steroids stabilized lysosomes at pharmacological concentrations (10−4–10−6M) but lysed them at higher concentrations. Etiocholanolone, a steroid pyrogenic in man, had no stabilizing effect. The concentration of steroid would therefore seem critical in determining its subcellular action. Experiments with albumin suggest that anti-inflammatory steroids (at 5 × 10−4M) have little effect in aiding its thermal denaturation whereas other steroids greatly increase denaturation. Increasing concentrations of cortisol and prednisolone however caused greater denaturation of albumin. Although the correlation between albumin solutions and lysosomal membrane proteins is tenuous it is suggested that the lytic effect of anti-inflammatory steroids could be due to protein denaturation. Their stabilizing effect, however, probably involves steroidlipid interactions.
The actions of some non-steroidal drugs on lysosomes
Authors: Lewis D A
Published: April 2011

Several non-steroidal acidic anti-inflammatory drugs had a lytic action on lysosomes at high concentrations but no apparant action at lower concentrations. The drugs also inhibited acid phosphatase activity but only at high concentrations. High concentrations of drugs accelerated the thermal denaturation of albumin solutions but partially protected the albumin against denaturation at lower concentrations. The possibility that the denaturing action of drugs on proteins at high concentrations is related to lysosomal damage and that this damage may be associated with ulceration in vivo is discussed. Salicylate was found to inhibit the stabilizing action of cortisol on lysosomes.
Formulation and pharmacological studies of a controlled release pentagastrin injection
Authors: Wai K N , Gerring E E L , Broad R D
Published: April 2011

Four formulations were designed to release pentagastrin at different rates after subcutaneous injection. These formulations were tested in vitro for rate of diffusion across a dialysis membrane into pH 7·3 phosphate buffer, and in vivo in rats for rate of excretion in the bile and on dogs for pharmacological responses. Good agreement was observed between the in vitro data, elimination rate and dose response data for the rate of release and duration of action of the four formulations. The results agreed with the theory that by controlling the rate of release of a short acting drug, one could sustain the pharmacological response to the drug and increase the total response by better utilization of an administered dose.
Preparation of active, drug-metabolizing, microsomal enzymes under optimal conditions and by iso-electric precipitation
Authors: Mitchard M
Published: April 2011

The influences of homogenization technique and of relative centrifugal force on the enzyme activity of hepatic microsomes have been investigated to establish optimal conditions for preparation. In general, a glass or Ultra Turrax homogenizer provided a satisfactory homogenate having maximal enzyme activity when nuclear and mitochondrial material were removed by centrifugation at >6500 g for 20 min. Esterase, UDP-transglucuronylase, reductase and oxidase activities of microsomes prepared from liver breis under optimal conditions from guinea-pig, rabbit and rat have been compared. The enzyme activities in microsomes prepared by isoelectric precipitation at pH 5·0 were similar to those prepared by differential centrifugation except for a 50–75% reduction in glucuronyl transferase activity observed in rabbit and guinea-pig.
The relation between the uptake of cetyltri-methylammonium bromide by Escherichia coli and its effects on cell/growth and viability
Authors: Salt W G , Wiseman David
Published: April 2011

The effects of CTAB uptake on cells of E. coli have been examined in terms of growth inhibition and decrease in cell viability. Different thresholds of CTAB uptake exist below which no effect on cell growth or viability could be detected and there was a distinct separation of the two effects. It is suggested that both reflect all or none responses by individual cells. A mechanism for the mode of antibacterial action of CTAB against E. coli is postulated.
A test for the assessment of the duration of the action of neostigmine and of the relative potencies of various anticholinesterases using the pupil of the mouse
Authors: Schneider R
Published: April 2011

The miotic effect of anticholinesterases was used to monitor the duration of their activity and to compare the relative potency of different members of this group. Female albino mice were used and the diameter of their pupils measured with the help of a monocular microscope at a magnification of × 60. After a suitable control period, readings were taken at 30 min intervals. This test was found to be superior to previous tests described for the same purpose.
Infrared identification of some hallucinogenic derivatives of tryptamine and amphetamine
Authors: Mesley R J , Evans W H
Published: April 2011

The use of infrared spectroscopy for the identification of psychotomimetic derivatives of amphetamine and tryptamine is discussed. Numerous characteristic absorptions are assigned on the basis of spectra recorded from 123 bases and salts. These permit the recognition of compounds of these types even when no reference materials or spectra are available. Distinction between the spectra of optically active and racemic forms of some amphetamine derivatives is also possible.
Some observations on the use of fatty alcohols and fatty acids to increase the consistency of oil-in-water emulsions
Authors: Talman F A J , Rowan Miss E M
Published: April 2011

A range of fatty alcohols and fatty acids of different chain lengths and chemical configuration has been examined to determine which of these may be usefully employed to increase the consistency of liquid paraffin-in-water emulsions stabilized by condensed complex films. Of the alcohols, a straight chain of 16 carbon atoms (cetyl alcohol) or a physical mixture of straight chains of 16 and 18 carbon atoms (cetostearyl alcohol) gave maximum bodying action. To a lesser extent a straight chain of 14 carbon atoms (myristyl alcohol) and in some cases a straight chain of 12 carbon atoms (lauryl alcohol) also increased the consistency of emulsions. Other homologues (C8, C10 and C18), unsaturated or branched chain alcohols and fatty acids were, in general, found to be of little value for this purpose.
A comparison of the effects of 6-hydroxy-dopamine immunosympathectomy and reserpine on the cardiovascular reactivity in the rat
Authors: Finch L , Leach G D H
Published: April 2011

In the conscious rat, 6-hydroxydopamine, or reserpine (5 mg/kg) pretreatment produced a marked fall in the mean systolic blood pressure whilst immunosympathectomized rats had resting blood pressures just below that of control animals. In pithed preparations, 6-hydroxydopamine treatment or immunosympathectomy potentiated the pressor responses to injected noradrenaline; reserpine pretreatment did not potentiate the noradrenaline response to the same degree. Tyramine responses were abolished after 6-hydroxydopamine or reserpine pretreatment but were unaffected by immunosympathectomy. Stimulation of the sympathetic outflow by the Gillespie & Muir (1967) preparation was abolished after 6-hydroxydopamine and reserpine pretreatment, and reduced after immunosympathectomy. It is concluded that 6-hydroxydopamine produces a destruction of the sympathetic nerve endings, abolishing the physiological uptake process and, therefore, producing supersensitivity to injected noradrenaline. Immunosympathectomy, although showing a marked reduction in sympathetic nerve supply leaves a functional uptake process. Reserpine (5 mg/kg), given 6 h previously, depletes endogenous catecholamines without significantly altering the sensitivity to injected noradrenaline, the uptake process remaining functional.
Potentiation of oxotremorine lethality by antihistamines
Authors: Gerald Michael C , Maickel Roger P
Published: April 2011

Antihistamines, representing the major chemical classes, administered intraperitoneally to mice in non-toxic doses potentiated the lethal effects of an LD10 dose (3·5 mg/kg) of oxotremorine in a dose related manner. Atropine and methylatropine were highly effective in blocking oxotremorine lethality alone and when it was potentiated by antihistamines. The antagonism by methylatropine suggests a peripheral site of toxicity. Antihistamines might enhance lethality by interfering with the inactivation of oxotremorine by liver microsomal drugs enzymes in a manner similar to SKF 525A.
Colorimetric determination of amphetamine salts in dosage forms
Authors: Fontani Febo , Morandini Franco
Published: April 2011

A colorimetric method for the determination of primary amines has been applied to the assay of amphetamine salts in dosage forms. Aqueous solutions of amphetamine salts heated in acidic medium with 2,5-dimethoxytetrahydrofuran and subsequently reacted with p-(dimethylamino)benzaldehyde, give a red colour. This reaction is useful for photometric determinations at 557 nm. Secondary and tertiary amines do not interfere.
The determination of sodium aminosalicylate in cachets of sodium aminosalicylate and isoniazid by ultraviolet absorption
Authors: Clough D
Published: April 2011

Sodium aminosalicylate can be determined in the presence of isoniazid by its ultraviolet absorption at 299 nm. The method is at least as accurate as the B.P.C. 1968 bromination method for cachets of sodium aminosalicylate and isoniazid. Analysis of a powder mix containing sodium aminosalicylate (2 g) and isoniazid (50 mg) gave a mean value of 2.02 ± 0.01 (s.d.) for ten determinations using the proposed method. The B.P.C. method gave a mean value of 2.03 ± 0.33 (s.d.). The proposed method has the advantage that the determination is independent of the isoniazid content and is more rapid than the official method. It can be easily adapted for automatic analysis.
Acid gastric secretory responses to histamine, crude porcine gastrin and pentagastrin in rats
Authors: Amure B O , Omole A A
Published: April 2011

The log dose-response curves for graded doses of the secretagogues porcine gastrin (a partially purified sample; the crude and its gastrin II equivalent), histamine, and a gastrin pentapeptide (pentagastrin) on the perfused stomachs of urethanized rats are parallel. On weight basis, pentagastrin is 60 times and histamine four times more active than the crude porcine gastrin preparation. The partially purified porcine gastrin sample is six times more potent than histamine but half as potent as pentagastrin. On molar basis gastrin (as the pure porcine gastrin II) has 3000 times the activity of histamine dihydrochloride and 5000 times that of the histamine base. Gastrin is 50 times more potent than pentagastrin. Gastrin and pentagastrin are more potent and have less undesirable side-effects than histamine.
Temperature changes occurring during the compression and recompression of solids
Authors: Travers D N , Merriman M P H
Published: April 2011

Measurements of the temperature rise occuring on compression, recompression and relaxation of compacts formed from Asagran, sodium chloride and boric acid have been made by means of thermocouples inserted into the compressed materials. There are marked differences in temperature rise for the different compacts when compressed to a final force of 50 kN (5 tons). With all compacts there was a rise in temperature on initial compression and a fall in temperature on relaxation. The rise could be separated into two components—that due to compact formation plus a further rise due to its elastic compression. The fall in temperature is thought to result on release of the strain energy stored in the compact. The rise in temperature on recompression followed by the fall of relaxation could be repeated many times on the same compact. Both rise and fall were directly proportional to the final compression force used. The fall on relaxation appeared to be numerically less than the rise on recompression for compacts of boric acid and Asagran. Lubrication of Asagran with magnesium stearate had little effect on the temperature rises.
The effect of particle shape on the variation of fill of a tabletting die
Authors: Ridgway K , Scotton Janet B
Published: April 2011

A 12 mm die cavity has been repeatedly filled from batches of granular material of a range of particle shape and size distributions. The variance in the weight contained by the die was determined from the replicates. The variance, expressed as a coefficient of variation to allow for differences in the means of groups of replicates, increased from 0·2635 to 0·7222 as the particle shape, expressed as the Heywood shape coefficient, increased in irregularity from a value of 8 to 13. The mean contained weight was greater for regular than for irregular particles, and a maximum die fill occurred where the ratio of die diameter to particle diameter was about 20 for all particle shapes.
The surface hardness of tablets
Authors: Ridgway K , Aulton M E , Rosser P H
Published: April 2011

A pneumatic micro-indentation apparatus has been used to determine the hardness of tablets of aspirin at various points on their diameter. All the tablets were 13 mm diameter; the compaction pressure and the particle size of the initial material were varied. The compression was carried out in a Perspex die so that radial pressure could also be assessed during compaction. The micro-indentation apparatus measured the total deformation at the loaded point on the tablet, and also the elastic recovery when the load was removed.
The influence of wet and dry granulation methods on the pore structure of lactose tablets
Authors: Selkirk Alastair B , Ganderton David
Published: April 2011

The conditions of wet granulation influenced the pore structure of lactose tablets, prepared over a wide range of tabletting pressures. Dry granulation, on the other hand, only influenced pore structure when slugging pressures were high, the granules were coarse and tabletting pressures were low. Mercury porosimetry revealed intense granule fragmentation when dry granulated materials were compressed. The effect of the change of pore size distribution on liquid penetration into tablets is discussed.
The effect of temperature on the solubilities of testosterone propionate in low polarity solvents
Authors: Bowen D B , James K C
Published: April 2011

The solubilities of testosterone propionate have been determined between 25 and 100° in 15 solvents and compared with theoretical values obtained from regular solution theory. Entropy considerations show that solvent-solute interactions occur in some solvents, increasing the solubility and resulting in deviations from regular solution behaviour. “Regular solutions” are obtained only in saturated hydrocarbon solvents, and the solubility is more accurately predicted as the temperature approaches the melting point, and as the molar volumes of solvent approach that of the solute.
Nuclear magnetic resonance studies on micelle formation by promethazine hydrochloride
Authors: Florence A T , Parfitt R T
Published: April 2011

The pmr spectra of solutions of promethazine hydrochloride in D2O have been obtained as a function of concentration above and below the critical micellar concentration of the drug. Chemical shifts were obtained relative to an external standard of a 20% promethazine solution (micellar). The shifts of the spectrum of the hydrophilic NH(CH3)2 group to higher fields on increasing concentration were explained by the increased dissociation of the group at the micelle surface, an effect illustrated by the decrease in bulk pH at the critical micelle concentration. Diamagnetic shifts of the aromatic ring protons are compatible with the non-polar environment and a parallel stacking of the phenothiazine rings in the interior of the micelle.
The correlation of unsteady-state heat transfer data from a sterilizing oven
Authors: Peacock D G , Ridgway K
Published: April 2011

Data, showing the pattern of temperature rise in articles undergoing sterilization in an oven under normal working conditions, have been studied. Simple mathematical models, each expressed in terms of a set of differential equations rather than in an explicit analytical form, have been fitted to these data, and the quality of fit and possible applications are here discussed.
Grade variation in the rheology of white soft paraffin B.P.
Authors: Barry B W , Grace A J
Published: April 2011

The rheology of six grades of white soft paraffin B.P. at 25° has been investigated using continuous shear viscometry and a creep viscometer. Temperature effects between 25° and 50° have been measured in continuous shear, and activation energies from 14·0 to 25·3 k cal mol−1 (58·6 to 105·9 k J mol−1) have been determined. Working the samples on a triple roller mill at 25° was found to decrease the apparent viscosity and, initially, to increase the yield stress. Five of the grades were linear viscoelastic, one was non-linear viscoelastic. The nature of ductility and its relation to measured rheological parameters have been discussed. Creep viscometry data gave a better correlation with the manufacturer’s data than did continuous shear measurements.