bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central muscle relaxant properties of 2,6-dimethylphenethylurea and related compounds
Authors: Green A L , Willey G L 
Published: April 2011

Abstract
Twenty-eight phenylalkylureas with alkyl, hydroxy, methoxy or chloro-substituents in the aryl ring have been synthesized and tested for central depressant and muscle relaxant properties. In this series, the dimethylphenethylureas with at least one ortho-methyl group show unexpectedly selective muscle relaxant activity. 2,6-Dimethylphenethylurea inhibits polysynaptic reflexes more readily than monosynaptic ones, but also depresses muscle contractions by an action independent of its effect on interneuronal transmission. It is a weak anticonvulsant, suppresses rage episodes in “fighting” mice, and has no selective blocking action on conditioned responses. It thus has a pharmacological profile resembling those of mephenesin and meprobamate, but distinct from either, and differing still more from those of phenobarbitone, chlordiazepoxide or chlorpromazine. However, tolerance to its action develops readily.
The use of the in vivo trachea preparation of the guinea-pig to assess drug action on lung
Authors: Lynn James G W 
Published: April 2011

Abstract
A method for recording the effects of drugs on an isolated in vivo segment of trachea and on lung pressure of a deeply anaesthetized animal is described. Acetylcholine, angiotensin, histamine, 5-hydroxytryptamine, prostaglandin (PG) F2α and slow-reacting substance of anaphylaxis, but not bradykinin, caused an increase in tracheal segment pressure and an increase in lung pressure. Bradykinin caused an increase in lung pressure but a fall in tracheal segment pressure. It was concluded that bradykinin acts mainly on the smaller airways and PGF2α mainly on the larger airways. The tracheal segment responded to adrenaline, aminophylline, ephedrine, isoprenaline, papaverine, PGE1 and PGE2. Propranolol reduced or abolished responses to all these bronchodilators except PGE1 and PGE2.
Effect of nialamide and methyldopa on the analgesic action of morphine in rats and mice
Authors: Contreras E , Tamayo L , Quijada L 
Published: April 2011

Abstract
Methyldopa and nialamide enhance the analgesic action of morphine when administered separately in the rat. However, the association of both drugs in the same animal diminishes the effect of the analgesic. Results observed in mice differ from those found in rats, whereas methyldopa induces a slight increase in morphine analgesic effect, nialamide is ineffective. The administration of both drugs in combination increases morphine effect in a way similar to that obtained when methyldopa and morphine are administered together.
Structure-activity relations in analgesics based on 4-anilinopiperidine
Authors: Casy A F , Hassan M M A , Simmonds ALMA B , Staniforth D 
Published: April 2011

Abstract
The synthesis of some 1-alkyl and l-aralkyl-4-(N-phenylpropion-amido)piperidines and related derivatives is described and the hot-plate activities in mice of these compounds reported. Activity variations among 1-methyl, 1-benzyl, and 1-phenethyl derivatives resemble those of corresponding open-chain anilide rather than 4-phenyl-piperidine analgesics. Infrared and nmr data show the two nitrogen atoms of the 4-anilinopiperidine derivatives to be further apart than those of open-chain anilides in their respective preferred conformations; these results, together with the extreme potency difference between the N-phenethyl derivatives diampromide and fentanyl, show that the two classes are best regarded as mutually distinct types of analgesic.
The hardness and elastic modulus of some crystalline pharmaceutical materials
Authors: Ridgway K , Shotton E , Glasby J 
Published: April 2011

Abstract
The surface microhardnesses of single crystals of the following materials have been measured: aspirin, hexamine, sodium chloride, potassium chloride, urea, salicylamide and sucrose. A Leitz microhardness tester was used, with indentor loads of 25 g or less, in order to give indentations of less than 50 μm diagonal length and enable measurements to be made on single crystals. The compressive elastic modulus of some of the crystals was also determined using a “Techne” microtensile tester modified to work in compression. When the materials are listed in order of magnitude of Young’s modulus, this order is the same as when they are listed in order of magnitude for surface hardness.
The effect of crystal hardness on radial pressure at the wall of a tabletting die
Authors: Ridgway K , Glasby J , Rosser P H 
Published: April 2011

Abstract
The force transmitted to the die wall during the tabletting of seven crystalline pharmaceutical materials has been measured using a photoelastic technique. The Vickers hardness of these materials has also been measured. The compounds examined were aspirin, urea, hexamine, salicylamide, potassium chloride, sodium chloride and sucrose. The pressure on the die wall increases as the hardness value decreases. The Vickers hardness of the resultant tablets was also measured; aspirin and sodium chloride both showed the occurrence of work hardening in that the tablets had a greater hardness value than the parent crystalline substance.
The effect of particle shape on powder properties
Authors: Ridgway K , Rupp R 
Published: April 2011

Abstract
Sand in the size ranges 18–20 mesh, 30–36 mesh and 44–60 mesh has been separated by means of a vibratory shape-sorting table into fractions of different shape. The ratios of the surface area of the particles to their volumes-the shape coefficients-ranged from 8 to 15. For each fraction the following properties were measured: angle of repose, bulk density and rate of flow through an orifice. In all cases, with increasing departure from the spherical, the angle of repose increased, whilst the bulk density and flowability decreased. Improved methods are reported for the measurement of bulk density, angle of repose and specific surface area in the range 30–130 cm2/g.
Crystal growth studies involving phase transitions in aqueous drug suspensions
Authors: Pearson J T , Varney G 
Published: April 2011

Abstract
The growth of oxyclozanide crystals in quiescent suspensions has been monitored using the Coulter Counter. Increase in particle size is the result of an isothermal, solvent-mediated phase transition between two unsolvated polymorphs, one having a lower solubility than the other. Effects due to Ostwald ripening and temperature cycling are absent. Theophylline, which shows crystal growth in suspension by hydration, has been studied by photomicrography. Preliminary results indicate that the initial rate of growth in such systems may be qualitatively described in terms of steady-state diffusion theory.
Correlation of partition coefficients in n-heptane-aqueous systems with buccal absorption data for a series of amines and acids
Authors: Beckett A H , Moffat A C 
Published: April 2011

Abstract
Partition coefficients in n-heptane-0·1n sodium hydroxide or 0·1n hydrochloric acid have been determined for a series of amines and acids; linear relations between chain-lengths and the logs of their partition coefficients were found. The plot of alkyl chain-length against buccal absorption of some amphetamines and fenfluramines, when they were 1% unionized, was linear. There was also a linear relation between the logs of the partition coefficients and buccal absorption of the amines and acids when these were 1 and 10% unionized. Those amines and acids having similar partition coefficients, when equally unionized, were absorbed to the same extent in the buccal test over the pH range 4 to 9. During the test the pH at the surface of the buccal membrane was shown to be the same as that of the solution in the mouth. n-Heptane is considered to be equivalent in solvent properties to the buccal lipid membrane for the compounds used in the present test.
Urinary excretion of the drug and its main metabolite in man, after the administration of (±)-, (+)- and (-)-ethylamphetamine
Authors: Beckett A H , Brookes L G , Shenoy E V B 
Published: April 2011

Abstract
The urinary excretion of ethylamphetamine and its metabolite amphetamine was studied in man after oral administration of (±)-, (+)-, and (-)-ethylamphetamine hydrochloride. The rates of excretion of these amines are dependant on the pH of the urine. At acid values, the (+)-isomer is metabolized faster and to a greater extent than the (-)-isomer, which is excreted mostly unchanged. The effect of alkyl chain length on stereoselective metabolism of N-alkylamphetamines is discussed.
Metabolism, excretion and biological availability of 4‘-chloro-2-ethylaminopropiophenone
Authors: Beckett A H , Hossie R D 
Published: April 2011

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.