bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism, excretion and biological availability of 4‘-chloro-2-ethylaminopropiophenone
Authors: Beckett A H , Hossie R D
Published: April 2011

After oral administration of 4′-chloro-2-ethylaminopropiophenone to man, unchanged drug and the de-ethylated, reduced and reduced deethylated compounds were found in urine. Comparative urinary excretion studies after the oral administration of 4′-chloro-2-ethyl-aminopropiophenone in a sustained release form and in single or divided doses indicates that, when kidney tubular reabsorption is minimized, the biological availability of a drug can be followed by examining the excretion of either unchanged drug or metabolites formed quickly and directly from the administered drug.
A model for the influence of emulsion formulation on the activity of phenolic preservatives
Authors: Bean H S , Konning G H , Malcolm S A
Published: April 2011

Basic mathematical models are suggested for calculating the concentration of preservatives which is chemically available in the water of emulsions. It is influenced by the total concentration of preservative in the emulsion, the oil: water partition coefficient of the preservative, the oil: water ratio and the concentration of emulgent. The activity of the preservative is related to the concentration free in the water.
The haemolytic activity of sols containing progesterone solubilized by phosphatidylcholine and lysophosphatidylcholine
Authors: Kellaway I W , Saunders L
Published: April 2011

Lysis of rat erythrocytes by aqueous dispersions containing lysophosphatidylcholine (lpc), phosphatidylcholine (pc) and progesterone has been studied. The haemolytic activity of lpc was reduced by saturating it with progesterone; mixed lpc-pc micelles owed their lytic activity to the lpc alone. Cholesterol solubilized together with progesterone by lpc greatly reduced the lytic activity of the lpc, and when solubilized with progesterone by a 1:1 mixture of lpc and pc, prevented haemolysis. Triolein also inhibited the haemolytic properties of the sols.
The metabolism of thioamides by the supernatant fraction of rat liver homogenate
Authors: Gibson M J , Hunter W H
Published: April 2011

α-Phenyl-α-(2-pyridyl) thioacetamide (SC 15396; antigastrin) is metabolized by the supernatant fraction of rat liver homogenate to give two metabolites. The major metabolite has been identified as α-phenyl-α-(2-pyridyl)acetonitrile. Three other thioamides, analogues of SC 15396 also give the corresponding nitriles in these conditions.
Further structure-activity relations of heterocyclic analogues of hemicholinium-3
Authors: Benz F W , Long J P
Published: April 2011

The importance of the 3-methyl group on the pyridinium ring of bis-quaternary nitrogen salts for hemicholinium-3-like activity having been conditionally established (Benz & Long, 1969a, b), derivatives containing classical isosteres of the 3-methyl group and the three oxidation states of the 3-methyl group were examined. Oxidation of the 3-methyl group to -CH2OH decreased activity tenfold. Subsequent oxidation to -CHO and -COOH further decreased activity. When the 3-methyl group was replaced by a halogen, activity was maintained by the iodo-derivative but decreased as the size of the halogen decreased and as the electronegativity increased. Substitution of an ethyl group for the 3-methyl decreased activity twofold, whereas replacement with -OH eliminated activity.
Some pharmacodynamic effects of the nematocides: methyridine, tetramisole and pyrantel
Authors: Eyre P
Published: April 2011

Methyridine, tetramisole and pyrantel affect several cholinergic mechanisms. In the rabbit, methyridine and tetramisole cause hypotension which is partially antagonized by atropine. In the cat, tetramisole causes an increase in blood pressure and causes prolonged contraction of the nictitating membrane. The evidence indicates that tetramisole may release catecholamines from the adrenal medulla. Pyrantel contracts the nictitating membrane; an effect which is abolished completely by hexamethonium. The three anthelmintics block neuromuscular transmission in a way which is characteristic of non-competitive depolarizing agents. They also inhibit cholin-esterases. These pharmacological data correlate closely with the reported clinical signs of the toxicity of these agents.
The in vivo and in vitro effect of diphenylhydantoin and phenobarbitone on K+-activated phosphohydrolase and (Na+, K+)-activated ATPase in particulate membrane fractions from rat brain
Authors: Formby Bent
Published: April 2011

The effect of diphenylhydantoin and phenobarbitone on a K+-activated phosphohydrolase, hydrolysing the artificial substrates p-nitrophenylphosphate and acetylphosphate, and (Na+, K+)-activated ATPase in particulate membrane fractions from rat brain, has been studied. Diphenylhydantoin was given orally over 20 weeks without any effect on these enzymic activities, whereas orally phenobarbitone significantly decreased the enzymic activities in the particulate membrane fractions containing synaptosomes, nerve endings and microsomes. In vitro, diphenylhydantoin inhibited the enzymic activities in the synaptosomal membrane fraction, but phenobarbitone did not. Several possibilities for the in vivo action of diphenylhydantoin are outlined; these are mainly concerned with a blocking of the passive movement of sodium into the cell. The in vivo effect of phenobarbitone is possibly a secondary pharmacological effect interfering with the utilization of ATP either directly or indirectly by a depression of some energy dependent processes such as protein synthesis.
Prevention of the reserpine effect on rat salivary gland noradrenaline by inhibitors of monoamine oxidase and catechol-O-methyl transferase
Authors: Jonason Jan
Published: April 2011

The roles of monoamine oxidase and catechol-O-methyl transferase for the inactivation of noradrenaline after reserpine treatment have been investigated in rat salivary glands in vivo. Inhibition of monoamine oxidase by nialamide retarded the reserpine-induced disappearance of noradrenaline in the glands, whereas inhibition of catechol-O-methyl transferase by 4-tropolone acetamide did not. However, when both enzymes were inhibited, reserpine produced a significantly slower disappearance rate of noradrenaline compared with inhibition of monoamine oxidase alone. Thus, after reserpine, most of the noradrenaline is metabolized by monoamine oxidase. When this enzyme is inhibited catabolism by catechol-O-methyl transferase appears to play a part in the reduction of noradrenaline induced by reserpine.
The interaction of hemicholinium-3 and oxotremorine in isolated organ preparations
Authors: György L , Pfeifer A K , Kenyeres J
Published: April 2011

On isolated ileum preparations of the rat and guinea-pig, hemicholinium-3 antagonizes contractions elicited by acetylcholine and oxotremorine to the same extent. Hemicholinium-3 was a mild antagonist to acetylcholine but a stronger one to oxotremorine and carbachol on the ileum of the rabbit. Whereas hemicholinium-3 has no anti-acetylcholine activity on the isolated urinary bladder of the rat, it antagonizes the contractions elicited by oxotremorine and carbachol, and acetylcholine after eserine. Morphine has an anti-oxotremorine activity on this organ. Increasing concentrations of oxotremorine release increasing amounts of acetylcholine from the rat isolated intestine.
Specific blockade of spasmogens by β-receptor stimulation with nylidrin and isoprenaline
Authors: Deshpande V R , Jadhav J H
Published: April 2011

Nylidrin, a β-adrenoreceptor stimulant drug, blocks the spasmogenic action of acetylcholine, histamine and barium on guinea-pig ileum in vitro and bronchial muscles in vivo. This action is antagonized by the β-receptor blocking agent, propranolol. It is suggested that the antispasmodic effect of nylidrin is mediated through the activation of β-receptors. Nylidrin seems to be less potent but longer acting in its antispasmodic action than isoprenaline.
Cutaneous vascular permeability factors (histamine, 5-hydroxytryptamine, bradykinin) and passive cutaneous anaphylaxis in sheep
Authors: Eyre P
Published: April 2011

The cutaneous blood vessels of sheep are more sensitive to histamine than those of laboratory rodents. The threshold dose in sheep was 0·0025 μg histamine. The ovine vessels are 70 to 100 times less sensitive to 5-hydroxytryptamine (5-HT) than to histamine, but only four times less sensitive to bradykinin than to histamine. The effects of compound 48/80 are antagonized both by the antihistamine agent mepyramine and by the anti-5-HT agent methysergide, which suggests that compound 48/80 may release 5-HT in addition to histamine in sheep. The capillary-damaging effects of passive cutaneous anaphylaxis in sheep are antagonized by methysergide and by sodium meclofenamate—an agent which antagonizes kinins and slow-reacting substance. The antihistamine agent mepyramine has a small anti-anaphylactic effect, whereas promethazine—a less specific antihistamine—offers more protection to the blood vessels against local anaphylaxis. It is concluded that in the complex interaction of chemical mediators of anaphylaxis in the cutaneous blood vessels of sheep, 5-HT and kinin (and/or SRS-A) may be more important than histamine.
Neuromuscular blocking agents. Replacement of quaternary ammonium groups in bis-onium compounds by amidinium, guanidinium, thiouronium, sulphonium and sulphoxonium groups
Authors: Bamford D G , Biggs D F , Chaplen P , Davis M
Published: April 2011

The quaternary ammonium groups of suxamethonium have been replaced by amidinium, guanidinium and thiouronium groups. The guanidine compound exhibited competitive neuromuscular activity of a low order of potency; the other compounds were ineffective. Replacement of the quaternary ammonium groups in decamethonium by ethylmethylsulphonium or dimethylsulphoxonium groups gave less potent, depolarizing agents.
Effects of some phenothiazines, tricyclic antidepressants and antihistamines on red cell agglutination
Authors: Tait B
Published: April 2011

The observation that promethazine hydrochloride inhibited red cell agglutination in the ABO blood group system led to the screening of a series of drugs structurally related to promethazine in an attempt to establish a structure activity relation. Standard group O serum agglutinated group A and group B cells. The serum in each test was pretreated with drug and the degree of agglutination on the slide was assessed by both direct and microscopic means. All phenothiazines tested possessed this property except thiopropazate and the cyclic compound MO967C. Several tricyclic antidepressants and antihistamines tested possessed inhibitory activity, the tricyclic compounds were generally as active as the phenothiazines but the antihistamines varied in activity. The structure associated with maximum activity appeared to be a mono- or di-methyl substituted ethylamine or propylamine chain. However, the presence of the phenothiazine nucleus seems to strengthen activity suggesting that the overall shape of the molecule is important. Within the phenothiazine group there appeared to be a relation between basicity and inhibitory activity. It is suggested that the positively charged drug molecules in solution are attracted to the negative acidic groups on the red cell membrane thus inhibiting the formation of antibody-antigen complexes. The cyclization of the phenothiazine and the tricyclic compounds’ side-chain appears to abolish the inhibitory action. These findings may be of clinical importance with respect to ABO incompatibilities between mother and foetus and also in laboratory serum antibody studies.
The effects of drugs on barbiturate withdrawal convulsions in the rat
Authors: Norton P R E
Published: April 2011

The effects of drugs on barbitone withdrawal convulsions in rats have been examined. Morphine and mebanazine had no effect on audiogenically induced barbiturate withdrawal seizures. Alcohol, although suppressing the seizures, did not maintain drug dependence. Chlorpromazine prolonged the recovery period after the induction of the convulsions. Meprobamate, chlordiazepoxide and primidone substituted for the barbiturate and maintained drug dependence. 5-Hydroxytryptamine, when administered intraventricularly, tryptophan, α-methyl-p-tyrosine and ethosuximide reduced the severity of the withdrawal seizures. Reserpine and p-chlorophenylalanine greatly increased the severity of the seizures. Anxiolytic sedatives substituted for barbitone in dependent animals, other drugs studied affected barbiturate withdrawal convulsions in a way similar to other convulsive processes.
The application of nuclear magnetic resonance to pharmacological problems
Authors: Burgen A S V , Metcalfe J C
Published: April 2011

Nuclear magnetic resonance (nmr) was first discovered in the investigation of fundamental properties of matter but rapidly became an important method in chemical research because of the wealth of detail it is capable of giving about molecular structure. The application to purely biological problems is more recent, but a number of the basic techniques for studying biological systems are now established and more extensive use of the method is desirable.

This survey is intended to accomplish two ends. Firstly to show that the basic principles of nmr spectroscopy are straightforward and easy to understand, and secondly to show the main ways in which this technique can be applied to problems of drug binding.
The influence of corticosteroid pretreatment on anaphylactic bronchoconstriction in the guinea-pig
Authors: Hicks R
Published: April 2011

Previous reports that cortisone and related compounds exerted a small degree of protection against antigen-aerosol-induced anaphylactic reactions, have been confirmed. Optimal effects were obtained 16 to 24 h after corticosteroid pretreatment. Marked effects were obtained from the more potent glucocorticoids, particularly water-soluble compounds. Similar pretreatment decreased the severity and modified the form of anaphylactic bronchoconstrictor responses induced by intravenous administration of antigen. In guinea-pigs pretreated also with mepyramine, the corticosteroids suppressed the residual and presumably non-histamine component of the anaphylactic bronchoconstrictions. Anti-anaphylactic potency was correlated with glucocorticoid and anti-inflammatory activity. A suggested mode of action involves a combination of weak anti-histamine activity and inhibition of release of slow reacting substances of anaphylaxis.
A potent β-adrenoreceptor blocking drug: 4-(2-hydroxy-3-isopropylaminopropoxy)indole
Authors: Moore Glynne E , O’Donnell Stella R
Published: April 2011

4-(2-Hydroxy-3-isopropylaminopropoxy)indole (LB46) is a competitive β-adrenoreceptor blocking drug with a potency of between 4 and 7 times that of propranolol on the guinea-pig isolated trachea and atria (chronotropic effects). LB46 itself produces tracheal relaxation which may result from an indirect sympathomimetic action. The influence of uptake into adrenergic nerves on pA2 and pA10 values for LB46 and propranolol, when using noradrenaline as agonist drug, has been assessed from results obtained on trachea in the presence and absence of cocaine (10−5m). In the absence of cocaine the slopes of the regression of log (dose ratio —1) against negative log molar concentration of antagonist were less than the theoretical value of —1·0. In the presence of cocaine the slopes of these regressions approached —1·0. Thus values of (pA2-pA10) also deviated from the theoretical value in the absence of cocaine but approached it if cocaine was present in the bath fluid.
The activities of α- and β-adrenoceptive blocking agents in reducing intestinal relaxation due to sympathetic stimulation in the pithed rat
Authors: Parkes M W , Gerrard Christine A
Published: April 2011

A pithed rat preparation, stimulated electrically via the pithing rod left in position, was employed to examine the effects of drugs, administered intravenously, on relaxation of a loop of ileum. Relaxation due to injected isoprenaline could be largely blocked by propranolol but that due to nervous stimulation or injected noradrenaline was blocked to only a lesser extent by either propranolol or phenoxybenzamine alone. The combination of phenoxy-benzamine and propranolol was more effective against relaxation from nervous stimulation than either drug alone but was still not as effective against this as against noradrenaline, or as propranolol alone against isoprenaline. It is concluded that intestinal relaxation after nervous stimulation involves both α- and β-adrenergic activity, in variable proportions. Adrenoceptive antagonists are not as effective in blocking these receptors as they are for those concerned in relaxation after injected catecholamines.
A procedure for the analysis of illicit diamorphine samples
Authors: Curry A S , Patterson D A
Published: April 2011

A procedure for the analysis of illicit diamorphine samples is outlined, which consists of preliminary examination of the material by infrared spectrophotometry, followed by thin-layer and gas-liquid chromatography. Data for eighteen likely contaminants of samples are recorded.
The displacement of l-tryptophan and dipeptides from bovine albumin in vitro and from human plasma in vivo by antirheumatic drugs
Authors: Mcarthur J N , Dawkins P D , Smith M J H
Published: April 2011

l-Tryptophan occurs in a protein-bound and an unbound form in serum from normal subjects. The amino-acid is displaced from its binding sites in vitro by salicylate, phenylbutazone, indomethacin, prednisolone, chloroquine and gold salts and is virtually absent in serum obtained from patients with rheumatoid arthritis receiving therapy with antirheumatic drugs. Some dipeptides bind to bovine albumin in vitro and are displaced by salicylate. All the drugs displace l-phenylalanyl-l-phenylalanine from its binding to normal human serum in vitro.
Salicylate-induced inhibition of collagen and mucopolysaccharide biosynthesis by a chick embryo cell-free system
Authors: NAKAGAWA HIDEO , BENTLEY J PETER
Published: April 2011

The ability of a chick embryo cell-free system to synthesize collagen, mucopolysaccharide and non-collagen protein in the presence of sodium salicylate was studied. Added creatine phosphate together with endogenous creatine kinase was the ATP generating system. The incorporation of labelled proline or labelled glucose into collagen or mucopolysaccharide respectively depended on ATP level in the cell-free system used. Salicylate inhibited collagen and mucopolysaccharide synthesis to a greater extent than non-collagen protein synthesis. The ability of the cell-free system to hydroxylate labelled protocollagen was inhibited 50% by storage at −18°. Ferrous iron reversed this inhibition. Salicylate prevented the restoration of the enzyme activity by ferrous iron. Incorporation of radioactivity into hyaluronic acid, when labelled UDP-glucuronic acid and UDP-N-acetylglucosamine were supplied, was inhibited 17% by salicylate. Under the same conditions 47% inhibition of incorporation into chondroitin sulphate was seen. This suggests that UDP-N-acetyl-glucosamine-UDP-N-acetylgalactosamine epimerase is inhibited by salicylate.
The influence of test conditions on the disintegration time of gelatin capsules
Authors: JONES B E , COLE W V J
Published: April 2011

The British Pharmacopoeia test for capsule disintegration is basically the same test as that used to measure tablet disintegration and as such it has some shortcomings, particularly in the determination of the end point. The results were significantly affected by the capsule size, the nature of the test solution, the temperature, and whether single capsules were tested instead of groups of five. The effect of temperature on capsule solubility was demonstrated. A modified test was applied to both hard and soft capsule products selected from the British Pharmacopoeia. Recommendations are made for new specifications for an official pharmacopoeial test.
Application of orthogonal functions to spectrophotometric analysis of weakly absorbing compounds in tablets
Authors: ABDINE H , WAHBI A M , KORANY M A
Published: April 2011

Glenn's method of orthogonal functions has been applied to correct for irrelevant absorption during the analysis of tablets of chlorpheniramine maleate, phenyltoloxamine dihydrogen citrate, diphenhydramine hydrochloride and ephedrine hydrochloride. The results suggest that the method can be used for routine analysis.
Constituents of two varieties of Indian dill
Authors: SHAH C S , QADRY J S , CHAUHAN M G
Published: April 2011

Two varieties of Indian dill, Anethum sowa, are available. They differ morphologically and have a different oil composition. They have a low dillapiole content (12–15%) and have a high content of carvone-dihydrocarvone (50–64%).
The relation between the vapour pressure of a drug and its concentration emerging in the air stream from a nasal inhaler
Authors: ARMSTRONG P A M , CARLESS J E , ENEVER R P
Published: April 2011

A method of determining the absolute vapour pressures of volatile drugs and drug-adjuvant mixtures is described. The absolute vapour pressures of methylamphetamine, propylhexedrine and eucalyptol have been determined over a range of temperatures. The concentrations of these drugs emerging from a nasal inhaler system have also been measured under similar experimental conditions. From the inhaler results, it has been possible to derive values for the vapour pressures of the drugs in the system and compare them with absolute vapour pressure values. The derived pressures were lower than the absolute pressures at any given temperature. Nevertheless, there seems to be reasonable agreement among the latent heats of vaporization of the three drugs using either parameter. The factors that may give rise to the low values of derived vapour pressure are discussed. Mixtures of eucalyptol and methylamphetamine examined using the same techniques, show that both with the inhaler system and with mixtures of the pure drugs a similar liquid-vapour equilibrium exists. The vapour pressure-composition diagram constructed from either set of results shows a positive deviation from Raoult's law.
The drug release characteristics of various rectal suppositories as determined by specific ion electrodes
Authors: THOMAS W H , MCCORMACK R
Published: April 2011

Suppositories containing sodium phenobarbitone (200 mg) were manufactured with the following bases; cocoa butter, cocoa butter plus beeswax, Dehydag and polyethylene glycols. The release of sodium ions through a dialysis membrane was conveniently measured with a sodium-specific ion electrode. The method facilitates evaluation and comparison of suppository bases and allows continuous monitoring of the release of active ingredient.
Species-dependent effects of fenfluramine on the central nervous system
Authors: FUNDERBURK WILLIAM H , HASH AVERY M , HAZELWOOD JEAN C , WARD JOHN W
Published: April 2011

The cortical effects of fenfluramine and a metabolite, norfenfluramine, were studied in rabbits and cats. The parent compound produced slow waves in the e.e.g. which were compatible with sedation in cats. Norfenfluramine also produced slow waves and apparent sedation in cats, but neither compound produced marked changes in the cortical waves of rabbits. When cortical waves in both species were slowed with pentobarbitone, fenfluramine increased the frequency of the waves in rabbits but did not alter the frequency in cats. Both fenfluramine and the metabolite blocked cortical after-discharges in both species. There is no apparent explanation for the differences in the action of the two drugs in the two species.
The estimation of the “free” and “bound” acetylcholine content of rat brain
Authors: SLATER P
Published: April 2011

Rat brains, not frozen, were homogenized in saline solution containing physostigmine, and also cupric chloride to inhibit choline acetyl-transferase. When brains were homogenized for periods of up to 3 min, the amount of acetylcholine extracted was proportional to the duration of homogenization. After 3 min, there was no further significant increase in acetylcholine. The acetylcholine extracted in this way was termed “free”; whereas that remaining in the brain tissue and extracted by acid-ethanol solution was termed “bound”. The total amount obtained from each brain was not significantly different from the total amount extracted by a more conventional method from the brains of rats killed by rapid freezing in liquid air. This observation applied also to brains removed from animals during anaesthesia and convulsions.
The site of the inhibitory action of salicylate on protein biosynthesis in vitro
Authors: BURLEIGH MARY , SMITH M J H
Published: April 2011

Salicylate (10 mm) affects neither the transfer of the amino-acid from leucyl-tRNA into protein by rat liver polysomes nor the formation of the leucyl-tRNA. However, lower concentrations of salicylate inhibit the activities of other aminoacyl-tRNA synthetases. The most sensitive enzymes are those which incorporate glutamate, aspartate and histidine. It is suggested that salicylate interferes with the in vitro biosynthesis of protein by preferentially inhibiting the production of certain aminoacyl-tRNA species. The drug, in concentrations of 0·6 mm and above, inhibits the ATP-pyrophosphate exchange reaction promoted by individual amino-acids, including leucine.
Anti-acetylcholinesterase activity of some stereoisomeric aminobornanes
Authors: BECKETT A H , LAN NGIAM TONG , KHOKHAR ABDUL Q
Published: April 2011

Bornyl analogues of choline and acetylcholine with eclipsed cis- and trans-configurations displayed low inhibitory activity towards acetylcholinesterase catalysed hydrolysis of acetylcholine; cis-isomers were slightly better inhibitors than their trans-counterparts. (+)-Bornan-2-one-3-endo-yltrimethylammonium bromide with its oxygen atom and the quaternary ammonium group fixed rigidly in the gauche configuration is much more potent inhibitor than its enantiomorph.
The effect of starch type, concentration and distribution on the penetration and disruption of tablets by water
Authors: FRASER D R , GANDERTON D
Published: April 2011

The effect of starch type, and its concentration and distribution, on the pore structure of tablets of aspirin and magnesium carbonate has been measured using air permeability and liquid penetration techniques. The addition of starch had no significant effect on the pore structure of the dry tablet but caused disruption and alteration of this structure when penetrated by water. When each starch was incorporated into the granules in wet massing the rate of disruption decreased in the order potato, maranta, wheat, corn, waxy corn and rice; but a more complicated pattern was produced when the starch was added to the granules as a pre-dried powder. Maximum breakup efficiency of magnesium carbonate tablets was produced when 10 % potato starch was incorporated internally and the tablet compacted to a porosity of 28 %.
The modifying effects of a cationic surfactant on the rates of base catalysed hydrolysis of esters of different structures
Authors: MEAKIN B J , WINTERBORN I K , DAVIES D J G
Published: April 2011

The effect of a cationic surfactant, cetyltrimethylammonium bromide (CTAB), on the hydrolysis rates of four esters of different structure has been investigated. The esters used were ethyl p-aminobenzoate (EPAB), p-nitrophenyl acetate (PNPA), ethyl p-nitrobenzoate (EPNB) and p-aminophenyl acetate (PAPA). Association between the esters and the CTAB occurs so that above its cmc the surfactant modifies the rates of hydrolysis, increasing those of EPNB and PNPA and decreasing those of EPAB and PAPA. It thus appears that the type of group on the p-position of the aromatic ring plays a major role in determining the kind of effect brought about by the CTAB. Possible reasons to explain the two different effects that CTAB has on ester hydrolysis are put forward.
The analysis of nicotine-1‘-N-oxide in urine, in the presence of nicotine and cotinine, and its application to the study of in vivo nicotine metabolism in man
Authors: BECKETT A H , GORROD J W , JENNER P
Published: April 2011

A rapid quantitative assay for nicotine-1′-N-oxide in urine, in the presence of nicotine and cotinine, is reported. The urinary excretion of nicotine, cotinine and nicotine-1′-N-oxide was determined after nicotine had been administered in cigarette smoke, orally, or intravenously to subjects with either fluctuating, controlled acidic or controlled alkaline urinary pH. The urinary excretion of the N-oxide in 24 h from smokers under normal conditions was about half that of the cotinine excretion; more trans- than cis-diastereoisomer of nicotine-1′-N-oxide was excreted.
The effect of smoking on nicotine metabolism in vivo in man
Authors: BECKETT A H , GORROD J W , JENNER P
Published: April 2011

Nicotine and a basic metabolite, cotinine, were determined in the urine by gas-liquid chromatography after intravenous administration of (—)-nicotine hydrogen (+)-tartrate to groups of male and female smokers and non-smokers in whom the urine was maintained at an acid pH. The urinary recoveries of nicotine and cotinine from male smokers fell in two groups. One showed a lower recovery of both alkaloids than was seen with male non-smokers. The other showed a similar recovery of nicotine but more cotinine than the male non-smokers. Female smokers excreted less nicotine but more cotinine than female non-smokers. More nicotine but less cotinine was excreted by female non-smokers than by male non-smokers. The results show sex dependent metabolism of nicotine occurs in non-smoking humans and that smoking causes alterations in nicotine metabolism.
Buccal absorption as a parameter of analgesic activity of some p-substituted acetanilides
Authors: DEARDEN J C , TOMLINSON ERIC
Published: April 2011

The extent of buccal absorption of 16 p-substituted acetanilides is related parabolically to analgesic activity. The correlation is slightly better than that between log (partition coefficient) and analgesic activity. Thus, for this series of compounds at least, an in vivo partition test provides a slightly better parameter of biological response than does an in vitro test.
Membrane osmometry of solubilized systems
Authors: ATTWOOD D , ELWORTHY P H , KAYNE S B
Published: April 2011

The solubilization of decane, ethyl p-hydroxybenzoate, methyl anisate and p-hydroxybenzoic acid by aqueous micellar solutions of cetomacrogol 1000 has been examined by membrane osmometry and viscosity techniques. The effect of the solubilizates on the number-average micellar molecular weight, Mn, has been related to their site of incorporation in the micelle. Decane and methyl anisate are solubilized in the hydrocarbon core of the micelles and both compounds produce an increase in Mn up to a maximum value of 2·0 times 105, at a solubilizate concentration of approximately 80% of the saturation limit for each compound. This increase is shown to result from an increase in the number of molecules of both solubilizate and of surfactant per micelle. Further addition of solubilizate, to produce a saturation level in excess of 80%, results in a decrease in micellar size in both systems. The solubilization of ethyl p-hydroxybenzoate and p-hydroxybenzoic acid is thought to involve the oxyethylene region of the micelle and both solubilizates cause an increase in Mn owing to the inclusion of solubilizate into the micelle, the number of molecules of surfactant per micelle being unaffected by the solubilization process. Viscosity studies on the decane-ceto-macrogol-water system are interpreted as indicating no change in either micellar symmetry or hydration as a result of solubilization. A spherical model for the micelles is shown to be consistent with the experimental data.
A laser light scattering apparatus
Authors: PUGH W J , SAUNDERS L
Published: April 2011

The use of a low power helium-neon laser for light scattering measurements is described. The Rayleigh and Cabannes theories have been modified for polarized incident light. A new procedure is recommended for data when the solvent correction is relatively high. Using this method a precision of 4·7 % was obtained for the molecular mass of bovine plasma albumin in water, compared with 6·3 % for the more usual method.
Adsorption of phosphatidylcholine at the benzene-water interface
Authors: JOHNSON M C R , SAUNDERS L
Published: April 2011

Interfacial tensions between benzene solutions of egg-phosphatidyl-choline and aqueous bovine plasma albumin have been studied. The presence of the protein in the aqueous phase leads to a more rapid adsorption of the phospholipid at the interface, this being a result of interaction between the phospholipid and protein. The most probable mechanism for the interaction is discussed. The interfacial tensions between aqueous dispersions of egg-phosphatidyl-choline and pure benzene have also been determined. The results clearly indicate the effect of ultrasonic treatment in producing a stable aqueous phospholipid dispersion.
The particle-size of sulphadiazine produced by a solvent-change method
Authors: ELWORTHY P H , WORTHINGTON H E C
Published: April 2011

The factors affecting the particle-size of sulphadiazine produced by a solvent-change method of crystallization have been studied. The most important variables appear to be the degree of turbulence in the pipeline mixer used for the crystallization process, and the concentration of drug in the dimethylformamide injection solution. Mechanisms which can account for these, and other features of this crystallization method, are presented.
Inactivation of resistant Pseudomonas aeruginosa by antibacterial combinations
Authors: RICHARDS R M E
Published: April 2011

P. aeruginosa resistant to preservative concentrations of benzalkonium chloride, phenylmercuric nitrate and chlorocresol in nutrient broth was inactivated by using phenylethanol-antibacterial combinations. EDTA-antibacterial combinations also showed increased activity using benzalkonium and chlorocresol. P. aeruginosa resistant to 0·25% chlorbutol was inactivated using phenylethanol-chlorbutol combinations at concentrations which were ineffective alone. Similarly P. aeruginosa having an increased resistance to chlorhexidine was inactivated by phenylethanol-chlorhexidine combinations at concentrations that were ineffective alone. Phenylethanol showed a greater general usefulness than EDTA at the concentrations tested.
Phenylethanol enhancement of preservatives used in ophthalmic preparations
Authors: RICHARDS R M E , MCBRIDE R J
Published: April 2011

The growth rates of P. aeruginosa in subinhibitory concentrations of antibacterial preservatives alone and in combination with phenylethanol were determined by an extinction method. Phenylethanol enhances the effect of benzalkonium chloride on growing cultures of P. aeruginosa and the results have been confirmed by viable counts. A similar effect is shown by phenylethanol in combination with chlorbutol, chlorhexidine diacetate, chlorocresol, merthiolate, methyl and propyl hydroxybenzoate mixture and phenylmercuric nitrate.
The application of photoelastic techniques to a rotary tabletting machine
Authors: RIDGWAY K , ROSSER P H
Published: April 2011

Powders have been compacted on a rotary tabletting machine, using a Perspex die mounted above the die table, with an extended lower punch and a shortened upper punch. By high speed cine photography in polarized light, the fringes due to the radial stress in the die wall were recorded during compaction. At the same time, the upper and lower punch forces were monitored by instrumented pressure rollers coupled to a recording oscilloscope. The total information thus obtained was sufficient to enable compression cycles to be determined for the first time on a rotary machine.
Effect of nigral lesion on chlorpromazine-induced acceleration of dopamine synthesis from [14C]tyrosine
Authors: NYBÄCK HENRIK , SEDVALL GÖRAN
Published: April 2011

The nigro-neostriatal dopamine pathway of the rat brain was subjected to a unilateral stereotaxic lesion at the level of the hypothalamic-mesencephalic junction. Fifteen days after the operation endogenous dopamine and[14C]dopamine formed in vivo from [14C]tyrosine were reduced to about 15% in the striatum ipsilateral to the lesion. Twenty-four h after the lesion the contents of endogenous and labelled dopamine were about the same in the striata of both sides. Chlorpromazine (15 mg/kg) accelerated several fold the accumulation of [14C]dopamine formed from [14C]tyrosine in the striatum on the intact side. However, in the striatum on the side of the lesion, chlorpromazine did not increase the accumulation of [14C]dopamine. The results indicate that chlorpromazine accelerates dopamine synthesis in the striatum by an indirect mechanism, presumably by activating the nerve impulse flow in the nigro-neostriatal dopamine pathway.
The oestrogenic and anti-oestrogenic properties of ring methyl-substituted stilboestrols
Authors: CLARK E R , McCRACKEN ANNA M
Published: April 2011

3,3′,5,5′-Tetramethylstilboestrol (I) and its α,α′-dimethyl- (II) and α,α′-diethyl- homologues (III) have been tested for oestrogenic and anti-oestrogenic activity. α,α′-Diethyl-3,3′,5,5′-tetramethylstilboestrol (III), by the uterine weight assay in immature mice, is 2·1 times 10−4 times as potent as an oestrogen as 17β-oestradiol [fiducial limits (0·95) = 1·59 times 10−4 −2·74 times 10−4] but 3,3′,5,5′-tetramethylstilboestrol (I) and α,α′,3,3′,5,5′-hexamethylstilboestrol (II) were oestrogenically inactive at a dose of 0·8 mg. Compound III exhibited auto-inhibition of its own oestrogenic response at doses between 1·8 and 7·2 mg. None of the compounds tested inhibited the uterotrophic response to 17β-oestradiol. Compounds II and III, but not compound I, produced a highly significant inhibition of the vaginal cornification response to 17β-oestradiol when the test compounds (5 μg) and 17β-oestradiol were administered intra-vaginally in a single solution. It is suggested that the compounds II and III compete with 17β-oestradiol for the oestrogen receptor and that methyl groups positioned ortho to the phenolic hydroxyl group sterically interfere with the binding of the compounds to the oestrogen receptor, or with the initiation of the oestrogenic response, or both.
Identification and quantitative determination of some metabolites of methadone, isomethadone and normethadone
Authors: BECKETT A H , MITCHARD M , SHIHAB A A
Published: April 2011

Isomethadone and normethadone are metabolized by microsomal preparations of guinea-pig liver to yield 2-ethyl-1,4-dimethyl-3,3-diphenyl-1-pyrroline and 2-ethyl-1-methyl-3,3-diphenyl-1-pyrroline respectively. The structures of the pyrrolines were established (by comparison with the pyrroline derived from methadone) by thin-layer chromatography and by infrared and nuclear magnetic resonance spectral data. Methadone, isomethadone and normethadone are also metabolized to the corresponding N-oxides. A gas chromatographic procedure for the quantitative determination of unchanged drugs, cyclic metabolites and N-oxides of methadone, isomethadone and normethadone in microsomal homogenates is described. The N-oxides were reduced before analysis.
The distribution of methadone in man
Authors: ROBINSON ANN E , WILLIAMS FAITH M
Published: April 2011

The distribution of methadone and its metabolite, 1,5-dimethyl-3,3-diphenyl-2-ethylidene pyrrolidine, in man, postmortem, is presented. Quantitative data for methadone and the metabolite in blood, bile, urine, liver, kidney, spleen, lung and brain samples show that methadone blood concentrations range from 0·22–3·04 μg/ml and are less than in bile and urine. The metabolite is found particularly in bile and urine. The liver and kidney concentrations are approximately equivalent unless the survival time is reduced by the presence of another CNS-depressant drug. Lung tissue is the richest source of methadone and brain the poorest. Chromatographic data for three other methadone metabolites are included.
A note on the influence of diet in West Africa on urinary pH and excretion of amphetamine in man
Authors: WESLEY-HADZIJA B
Published: April 2011

The urinary excretion of amphetamine was examined after the oral administration of (+)-amphetamine sulphate to two groups of subjects whose urinary pH fluctuated about mean acidic or alkaline values due to their different diets. The group with a balanced protein diet giving acidic urine, excreted much more drug unchanged than the group with a low protein diet giving alkaline urine. A small increase in protein intake in the group with alkaline urine made their urine pH acidic in a few days and increased their excretion of amphetamine to the same level as the group with acid urine.
Decomposition of methoxamine in aqueous solution: Identification of the decomposition products
Authors: MILLARD B J , PRIAULX D J , SHOTTON E
Published: April 2011

Combined gas-liquid chromatography-mass spectrometry is used to study the decomposition of methoxamine. The major breakdown product in aqueous solution under air is shown to be 2,5-dimethoxy-benzaldehyde.
Structural differences in solutions derived from polymorphic modifications of aspirin
Authors: KILDSIG DANE O , DENBO RICHARD , PECK GARNET E
Published: April 2011

Differences in the structure of solutions derived from two polymorphic modifications of aspirin were demonstrated through differences in apparent pKa values. The apparent pKa's were determined in dimethylformamide using tetrabutyl-ammonium hydroxide as the titrant. The pKa differences were ascribed to differences in intra- and intermolecular hydrogen bonding of the solute.
Δ1-Tetrahydrocannabinolic acid, an important component in the evaluation of cannabis products
Authors: DE ZEEUW R A , MALINGRÉ TH M , MERKUS F W H M
Published: April 2011

The occurrence and some analytical properties of Δ1-etrahydrocannabinolic acid have been investigated, including its chromatographic behaviour in the presence of other cannabinoids. The acid is inactive but is converted on smoking into the active tetrahydrocannabinol. The acid is present in abundant amounts in various cannabis samples, marihuana in particular, and these will be more active on smoking than when administered by injection or orally. A method for the separate determination of tetrahydrocannabinol and its acid is also described.
The biliary excretion of tartrazine. Sex differences in the rat and species differences in the rat, guinea-pig and rabbit
Authors: GREGSON R H S , HIROM P C , MILLBURN P , SMITH R L , TURBERT H B , WILLIAMS R T
Published: April 2011

The excretion of tartrazine in the bile and urine has been studied in biliary cannulated rats, rabbits and guinea-pigs. This dye is excreted unchanged by these species. In the rat a sex difference in the relative amounts of tartrazine excreted in bile and urine has been found. Male rats excrete in 3 h about 17 % of an intravenous dose (50 μmol/kg) in the bile and about 70% in the urine, whereas females excrete about 40 and 45 % respectively. The biliary excretion of tartrazine in the rat appears to be influenced by dose level, for at the lower level of 4.5 μmol/kg male rats excrete about 9 % of an intravenous dose in the bile and 64% in the urine in 3 h, the corresponding values for female rats being 30% and 50%. There is also a species difference in the extent of biliary excretion of tartrazine (50 μmol/kg intravenously). The female rat and female guinea-pig excrete in 3 h about 40 % of the dose in the bile and a similar amount in the urine whereas the female rabbit excretes only 6% in the bile and nearly 70% in the urine. Previous work in this laboratory has shown that molecular weight is an important factor in the biliary excretion of foreign compounds and the present results fit in with this view.
A possible relation between pKa1 and lipid solubility and the amounts excreted in urine of some tobacco alkaloids given to man
Authors: BECKETT A H , GORROD J W , JENNER P
Published: April 2011

The amount of unchanged (—)-nicotine, (—)-nornicotine, (—)-methylanabasine and (—)-anabasine excreted in the urine after oral administration to man was dependent on urinary pH while that of (—)-cotinine depended on urinary pH and on urine flow rate. No unchanged β-nicotyrine, β-nornicotyrine or myosmine was detected in urine. More nornicotine and anabasine than their corresponding tertiary amines nicotine and methylanabasine were excreted unchanged in the urine. Correlations of pKa1 and lipid solubility and the urinary excretion of these compounds were made.
The effect of sugars on the temperature dependence of the critical micelle concentrations of cationic surfactants
Authors: ADDERSON J E , BUTLER C G
Published: April 2011

The temperature dependence of the critical micelle concentrations (cmc) of decyl, dodecyl and tetradecyl trimethylammonium and dodecyl benzyl dimethylammonium bromides in the presence of glucose or sucrose is reported. Thermodynamic parameters have been calculated using the uncharged phase-change model. An interpretation of the changes in cmc values, relative to those in simple aqueous solutions, is offered in terms of the resultant of two effects, namely modifications in water-structure and reduction of dielectric constant.
The absorption from the gut of quinine and chlorpheniramine given with various anionic agents
Authors: SUZUKI E , TSUKIGI M , MURANISHI S , SEZAKI H , KAKEMI K
Published: April 2011

The absorption of quinine and chlorpheniramine with anionic agents was examined in the rat rectum, small intestine and stomach. The enhancement of absorption was related to partition behaviour, to the organic solvent, and surface activity of ion-pair complexes, but it seems that with results from these properties alone it is not possible to explain the apparent increase in the in situ absorption of amines. In the presence of anionic agents, the absorption of amines was enhanced at all sites examined and kinetically the uptake to the mucosal membrane was increased in the rectum and small intestine. The effect of anionic agents on the uptake of amines was greater in the rectum than in the small intestine and this may be related to differences in the nature of the gut wall.
The preservation of ophthalmic solutions with antibacterial combinations
Authors: RICHARDS R M E , MCBRIDE R J
Published: April 2011

Solutions of pilocarpine, atropine and physostigmine preserved with benzalkonium, chlorhexidine, phenylmercuric nitrate (PMN), chlorocresol and chlorbutol in simple solution and in combination with either phenylethanol or disodium edetate (EDTA), were contaminated on two separate occasions with high inocula of P. aeruginosa. Phenylethanol-antibacterial combinations were consistently effective in killing the inoculum within 15 min except for one formulation with chlorhexidine and physostigmine salicylate and formulations with PMN for which sterilization times ranged from 30 to 90 min.
Effect of neuroleptic drugs on central catecholamine turnover assessed using tyrosineand dopamine-β-hydroxylase inhibitors
Authors: ANDÉN NILS-ERIK , CORRODI HANS , FUXE KJELL
Published: April 2011

The effects of some neuroleptic drugs on the noradrenaline turnover in the rat brain and spinal cord were studied biochemically and histochemically with the help of a new inhibitor of the enzyme dopamine-β-hydroxylase, bis(4-methyl-1-homopiperazinyl-thiocarbonyl) disulphide; (FLA-63). Haloperidol (1 mg/kg, i.p.), chlorpromazine (5–10 mg/kg, i.p.), pimozide (1–5 mg/kg, i.p.) and fluspirilene (1–5 mg/kg, i.p.) produced an acceleration of the noradrenaline disappearance induced by FLA-63. Clothiapine (1 mg/kg, i.p.) was ineffective. The lowering of brain dopamine after treatment with α-methyltyrosine methylester (H44/68) was markedly enhanced by haloperidol (5 mg/kg, i.p.) and slightly so by chlorpromazine (5 mg/kg, i.p.), whereas both drugs simultaneously caused a significant increase in the noradrenaline loss. Thus, the same results were obtained with dopamine-β-hydroxylase and tyrosine-hydroxylase inhibition on the influence of neuroleptic drugs on the noradrenaline turnover. The acceleration seen after haloperidol and chlorpromazine, but not after pimozide and fluspirilene, could be due to a compensatory activation of noradrenaline neurons produced by a noradrenaline receptor blockade.