bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of substituting tetrazole for carboxyl in two series of anti-inflammatory phenoxyacetic acids
Authors: DRAIN D J , DAVY B , HORLINGTON M , HOWES J G B , SCRUTON J M , SELWAY R A 
Published: April 2011

Abstract
Series of o-phenylcarbamoyl- and o-benzamido-phenoxymethyl tetrazoles and o-phenylcarbamoylphenoxyacetic acids have been synthesized. Anti-inflammatory activity was measured by the phenyl benzoquinone writhing test in mice and the rat foot carrageenan oedema test. Potency in the two o-benzamido substituted series could not be related with structure in a satisfactory manner. Introduction of substituents into the benzene rings of the o-phenylcarbamoyl substitued series led to complex changes. When the phenoxy ring was unsubstituted, introduction of meta- and para-substituents possessing high +ve π constants into the o-phenylcarbamoyl ring led to increased potency, and each tetrazole was appreciably more potent than the corresponding acid. When the o-phenylcarbamoyl ring was unsubstituted meta- and para-substituents with high +ve π constants introduced into the phenoxy ring caused increases in potency in the acid series but not in the tetrazole series, and each acid was more potent than the corresponding tetrazole. The two tetrazoles found to be the most active in the mouse writhing test 5-[2-(3,4-dichlorophenylcarbamoyl)phenoxymethyl]tetrazole (compound 12T, SNR.2337) and 5-[4-chloro-2-(3-trifluoromethylphenyl-carbamoyl)phenoxymethyl]tetrazole (compound 22T, SNR.2420) were selected for study in a series of other anti-inflammatory tests.
Neuromuscular blocking and ganglion blocking activities of some acetylcholine antagonists in the cat
Authors: BOWMAN W C , WEBB SANDRA N 
Published: April 2011

Abstract
The potencies of tubocurarine, gallamine, pancuronium, benzoquinonium, hexamethonium and mecamylamine in blocking neuromuscular transmission in the soleus muscle, and in blocking contractions of the nictitating membrane evoked by preganglionic sympathetic stimulation have been compared in cats under chloralose anaesthesia. On a molar basis, pancuronium was about 8 times and benzoquinonium about 2·5 times more potent than tubocurarine in blocking the soleus muscle; gallamine was less than half as potent, mecamylamine about 128 times and hexamethonium about 380 times less potent. In blocking the superior cervical ganglion, mecamylamine was about 17 times more, tubocurarine was about 5 times more and pancuronium about twice as potent as hexamethonium. Benzoquinonium was about half as potent as hexamethonium, and gallamine about 5 times less potent. The results emphasize that the shorter distance between charged centres, as in hexamethonium, reduces affinity for muscle receptors but does not necessarily enhance affinity for ganglion receptors, and from the point of view of deductions concerning the configuration of the ganglionic receptor, the ganglion blocking potencies of some neuromuscular blocking drugs should be taken into account.
The influence of formulation variables on phase inversion temperatures of emulsions as determined by a programmed viscometric technique
Authors: SUNDERLAND V B , ENEVER R P 
Published: April 2011

Abstract
A programmed temperature rise viscometric technique has been used to examine the influence of formulation variables on the phase inversion temperatures (P.I.T.) of oil-in-water emulsions stabilized with mixed polyoxyethylene alcohol surfactants. Using a heating rate of 0·5° min−1, the P.I.T. was defined either by a sharp change in apparent viscosity when recording shear stress-rate of shear rheograms for successive emulsion samples, or by the change in shear stress with time for a single emulsion sample. With an overall concentration of 6·00% w/w surfactant mixture of Brij 92 and Brij 96, the P.I.T. was found to rise in an approximately linear fashion as the HLB increased towards the optimum value. When the surfactant concentration was related to the aqueous or oil phase and these phase ratios varied, the P.I.T. changed in a complex manner. Water-soluble additives caused marked changes in the P.I.T. For example, 5·0% w/w sodium chloride depressed the P.I.T. by 17° and 5·0% w/w calcium chloride caused an 11° fall, whereas 2·0% w/w propylene glycol produced a 6° rise. These results followed the same trend as the cloud point of 1·0% w/w aqueous solutions of Brij 96 containing these additives. Linear correlations were obtained between the cloud point and P.I.T. data from which the effect of additives upon emulsion stability may be monitored.
Chemoprophylactic agents in schistosomiasis: eremanthine, costunolide, α-cyclocostunolide and bisabolol
Authors: BAKER P M , FORTES C C , FORTES ELIZABETH G , GAZZINELLI G , GILBERT B , LOPES‡ J N C , PELLEGRINO J , TOMASSINI T C B , VICHNEWSKI WALTER 
Published: April 2011

Abstract
The wood oils of the trees Eremanthus elaeagnus Sch.-Bip., Vanillosmopsis erythropappa Sch.-Bip. and Moquinea velutina Bong. inhibit penetration of cercariae of the trematode Schistosoma mansoni. The effect is due to the presence of α,β-unsaturated sesquiterpene lactones of which three, eremanthine (I), costunolide (III) and α-cyclocostunolide (V), have been characterized. The sesquiterpene alcohol (-)-bisabolol (II) present in two of the oils is weakly active while dihydro-β-cyclocostunolide (VI) which lacks the unsaturated lactone function is inactive. I and V react with the sulphydryl group of cysteine, and their activity may be related to inhibition of sulphydryl groups in cercarial enzymes.
Some actions of amantadine on peripheral tissues
Authors: HEIMANS R L H , RAND M J , FENNESSY M R 
Published: April 2011

Abstract
Amantadine has been tested on several peripheral preparations. It depressed responses of the chick isolated oesophagus to nicotine and preganglionic parasympathetic nerve stimulation without depressing responses to acetylcholine. It did not affect the amplitude or duration of action potentials in toad sciatic nerve. It enhanced the effects of noradrenaline and dopamine while reducing the effect of tyramine on the coaxially stimulated guinea-pig ileum, isolated central artery of the rabbit ear and spontaneously beating guinea-pig isolated atria preparations. Amantadine enhanced the depressor effect of dopamine in the rabbit.
Effects of amantadine on uptake and release of dopamine by a particulate fraction of rat basal ganglia
Authors: HEIMANS R L H , RAND M J , FENNESSY M R 
Published: April 2011

Abstract
Amantadine, in vitro, produced dose-dependent blockade of dopamine uptake into a synaptosome-rich particulate fraction of an homogenate of the basal ganglia of rats. A concentration of 3·6 times 10−6M was required to inhibit uptake by 50%. Diethazine was less potent in blocking dopamine uptake, the equiactive concentration being 8·0 times 10−6M. Amantadine and (+)-amphetamine in concentrations in excess of 10−5M caused the release of small quantities of added dopamine from the particulate fraction.
The assessment of β-adrenoceptor blocking potency and cardioselectivity in vitro and in vivo
Authors: BAIRD J R C , LINNELL JENNIE 
Published: April 2011

Abstract
The β-adrenoceptor blocking potencies and cardioselectivities (versus tracheal smooth muscle) of propranolol, practolol and M & B 17803A have been assessed on in vitro and in vivo guinea-pig preparations. Propranolol was found to be potent but non-selective, practolol to be less potent but cardioselective. M & B 17803A resembled practolol in potency but had a more modest degree of cardioselectivity in vivo. These observations suggest that the procedures used form a simple scheme which permits a probably relevant assessment of β-adrenoceptor blocking potency and cardioselectivity.
Effects of fenfluramine on the adrenergic system
Authors: BABULOVA A , COTILLO P , BONACCORSI A , PODVALOVA I 
Published: April 2011

Abstract
The influence of fenfluramine on sympathetic transmission has been examined in various intact and isolated preparations. Fenfluramine both facilitated and inhibited the responses elicited by the sympathetic stimulation according to the dose administered and the preparation used. Fenfluramine, to a lesser extent than amphetamine, antagonized, in some preparations, the neuron blocking action of guanethidine. Fenfluramine did not antagonize the sympathomimetic effects elicited by amphetamine in the isolated atria and the isolated vas deferens unless very high concentrations of both drugs were used.
A note on the identification of N-hydroxyphenmetrazine as a metabolic product of phendimetrazine and phenmetrazine
Authors: BECKETT A H , SALAMI M A 
Published: April 2011

Abstract
Phenmetrazine and the N-oxide of phendimetrazine have been demonstrated as metabolites in urine in man after oral phendimetrazine (Beckett & Watson, to be published). Recently, in studies of the in vitro metabolism of phenmetrazine and phendimetrazine by liver microsomes of various animal species, we observed a new product in high yields which could be separated from both amines by g.l.c. and t.l.c.; the new metabolic product gave a black spot on t.l.c. when sprayed with ammoniacal silver nitrate. The structure and characteristics of this new metabolic product are now reported.
Kinetics of interconversion of sulphamethoxydiazine crystal forms
Authors: MOUSTAFA M A , KHALIL SAID A , EBIAN A R , MOTAWI M M 
Published: April 2011

Abstract
A quantitative Nujol mull technique is described for the determination of sulphamethoxydiazine crystal forms in mixtures, so that the rates of their interconversion may be determined. The technique is applied to the transformations taking place in the more thermo-dynamically active as well as biologically available crystal form (Form II). Kinetic parameters indicate a highly temperature dependent transformation (Ea ⋍ 100 kcal mol−1; 418·6 kJ mol−1) of Form II to the more stable Form I. Suspension in water results in a much faster transformation of Form II (Ea ⋍ 20 kcal mol−1; 83·7 kJ mol−1, t1/2 ⋍ 15 min) to the water-stable Form III. Water and water vapour are shown to be important factors in the transformation of Form II at room temperature.
A two phase series model for the transport of steroids across the fully hydrated stratum corneum
Authors: YOTSUYANAGI T , HIGUCHI W I 
Published: April 2011

Abstract
A two phase series model for the permeability behaviour of the fully hydrated stratum corneum has been examined using Scheuplein's data on steroids, since these strongly encouraged the investigation of possible heterogeneous diffusion models that showed the dependence of the effective diffusion coefficient, De, upon the effective partition coefficient, Ke. The model described can be characterized by Ve and Vw, the volume fractions for the “cytoplasm” and the “cell wall” phases, Ke and Kw, the solute partition coefficients for the “cytoplasm” and the “cell wall” phases and De and Dw, the respective diffusion coefficient for the two phases. Reasonable correlations were found between the experimental Pe, effective permeability coefficient, values and the partition coefficients obtained with amyl caproate and those obtained with hexadecane. Also the magnitude of Dw was estimated and found to be about 10−13 and 10−11 cm2/s when the lipoidal nature of the cell wall was equated to hexadecane or amyl caproate. In general, reasonable self-consistencies among the various experimental results and parameters of the model were found.
Antihistamine-monoamine oxidase inhibitor interaction in rabbits
Authors: SINCLAIR JOHN G 
Published: April 2011

Abstract
The ability of a drug to produce a fatal hyperpyrexia in rabbits pretreated with a monoamine oxidase inhibitor (MAOI) may be predictive of a serious clinical drug-drug interaction. These interactions appear to be due to 5-hydroxytryptamine (5-HT) potentiation. Since some antihistamines have been shown to block the neuronal 5-HT uptake, several antihistamines were tested in phenelzine-pretreated rabbits. The alkylamines (dexchlorpheniramine, chlorpheniramine, dexbrompheniramine, brompheniramine and pheniramine) and the ethylenediamines (mepyramine and tripelennamine) were active in producing a fatal hyperpyrexia in the MAOI-pretreated rabbits. Diphenhydramine and triprolidine produced a fatal hyperpyrexia in approximately one half of the animals tested. The mechanism responsible for the interaction between chlorpheniramine, a representative of the active compounds, and phenelzine appears to be 5-HT potentiation. Antihistamines that did not produce a fatal hyperpyrexia in the phenelzine pretreated rabbits were: phenyltoloxamine, promethazine, methdilazine, trimeprazine, meclizine, chlorcyclizine, cyproheptadine, phenindamine and dimethpyrindene. The potential use of the active compounds as antidepressants is also discussed.
Investigations of the biosynthesis of novobiocin
Authors: CALVERT R T , SPRING M S , STOKER J R 
Published: April 2011

Abstract
The biosynthesis of novobiocin was investigated using isotopically labelled compounds. The amino-group of the coumarin unit was found to be derived from tyrosine, other typical 7-oxycoumarin precursors were not incorporated into the coumarin unit of novobiocin, 4′-hydroxyphenylpyruvate was a better precursor of the substituted benzoic acid unit than was 4′-hydroxycinnamic acid. A biosynthetic route to this unit of novobiocin is suggested. Synthetic pathways for 2′,4′-dihydroxyphenylalanine-1-14C and 4-hydroxybenzaldehyde-U-14C are reported for the first time.
Agitation of the solvent in tablet dissolution studies—a flow visualization technique
Authors: WITHEY R J , BOWKER A J 
Published: April 2011

Abstract
A flow visualization technique has been used to compare flow patterns in several kinds of dissolution apparatus in wide use. The technique readily reveals undesirable characteristics and provides a rational basis for judging empirically developed dissolution apparatus. Some undesirable mixing and flow characteristics were seen in all the methods examined. The U.S.P. apparatus appeared the most promising.
Some aspects of the failure of sucrose tablets
Authors: GROENWOLD H , LERK C F , MULDER R J 
Published: April 2011

Abstract
The effects of compression force, amount of magnesium stearate, carbowax and talc on the failure characteristic of tablets of sucrose granulation with gum acacia as binder have been examined. The results show that breakage of the tablets during ejection is accompanied by high ejection forces and low ratio of lower to upper punch force. Tablets with an upper bevelled edge capped at high applied forces unlike those prepared with a flat upper face. This may be due to high radial forces in the bevelled top at the end of the compression cycle, caused by the bevelled edge, resulting in break-down of interparticulate bonds formed during compression. At very high compression forces all tablets showed lamination because of axial expansion.
Determination of pharmacokinetic parameters for rapid and slow acetylators of sulphadimidine
Authors: VAN OUDTSHOORN M C B , POTGIETER F J 
Published: April 2011

Abstract
The pharmacokinetic parameters for twenty test subjects were determined after oral administration of sulphadimidine a urinary excretion method was used. The rate constant for the formation of acetylsulphadimidine shows that the acetylation polymorphism can be attributed to the rate of metabolism. The evidence of bimodality was also confirmed when expressing the data in terms of biological half-life rather than percentage acetylation. With seven test subjects more than 90 % of the sulphadimidine ingested was metabolized.
A comparison between the negative inotropic action of various antiarrhythmic drugs and their influence on calcium movements in heart muscle
Authors: GRAÇA A SILVA , VAN ZWIETEN P A 
Published: April 2011

Abstract
The influence of quinidine, lidocaine, (+)- and (±)-propranolol, l-(+)- and d-(–)-INPEA and (±)-alprenolol on contractile force and transmembraneous calcium exchange was studied in beating guinea-pig atria (3Hz) and in resting left auricles. Quinidine and lidocaine (5 × 10−5m) reduced the contractile force by approximately 34 and 19%, respectively. Both drugs diminished the Ca2+ flux during excitation without affecting the exchangeable fraction at equilibrium or the total Ca2+ content. In resting auricles both drugs did not influence the passive Ca permeability whatsoever. (+)- or (±)-Propranolol and alprenolol (5 × 10−5m) depressed the contractile force by approximately 60 and 33 % of the initial value, INPEA (both isomers) hardly showed negative inotropic properties. None of these β-adrenoceptor blocking agents significantly affected the calcium fluxes or the total Ca2+ content, either in beating atria or in resting auricles. The negative inotropic action of quinidine and lidocaine might be explained at least in part by the reduced rate of transmembraneous calcium exchange. For the β-adrenoceptor blocking compounds such a mechanism cannot be the cause of their depression of cardiac contractile force. It is suggested that the expression “quinidine like” effect is not adequate for the general description of the negative inotropic side effect of most β-adrenoceptor blocking and related drugs.
Antagonism of prostaglandin F2α induced bronchoconstriction and blood pressure changes by polyphloretin phosphate in the guinea-pig and cat
Authors: MATHÉ A A , STRANDBERG K , FREDHOLM B 
Published: April 2011

Abstract
Polyphloretin phosphate (PPP) when infused intravenously into guinea-pigs or cats antagonized the bronchoconstriction and blood pressure changes elicited by prostaglandin F2α and cat paw slow reacting substance (SRS). The dose required to induce a 50% reduction was 40–80 mg/kg PPP. The effects of histamine were not significantly antagonized by the doses used. PPP itself also had a blood pressure lowering effect. The results suggest that it may act as a prostaglandin and SRS antagonist in vivo.
The effect of β-phenethylamine upon spontaneous motor activity in mice: A dual effect on locomotor activity
Authors: JACKSON D M 
Published: April 2011

Abstract
The effect of intraperitoneal injections of β-phenethylamine on spontaneous motor activity in mice has been examined. Doses 75 mg/kg and higher produced a biphasic type of activity. A first phase of increased activity occurred about 5 min after injection, and a second about 30 min after injection. Pharmacological examination of these curves showed the first peak to be an indirect effect requiring newly synthesized noradrenaline, while the second peak appeared to be caused by a direct action. Thus it was not affected by reserpine, α-methyldopa, protriptyline, desipramine, disulfiram or α-methyl-p-tyrosine. These results suggest that phenethylamine differs from amphetamine in its effect on spontaneous motor activity.
Neuromuscular blocking and antimuscarinic activity of a series of bis-atropinium and N-n-alkyl atropinium compounds
Authors: GREEN D M , MUIR A W , POWER ROSEMARY A L , THOMPSON PAMELA B J 
Published: April 2011

Abstract
Measurements of neuromuscular blocking and antimuscarinic activity have been made in a series of bis-atropinium (BA) and N-n-alkyl atropinium (N-AA) compounds. That the second atropinium group contributed to the neuromuscular blocking activity of BA compounds was shown by the relative lack of such activity in the N-AA series of compounds. Peak neuromuscular blocking activity occurred when two atropinium groups were separated by a chain of either 10 or 11 methylene groups. Members of both series of compounds displayed antimuscarinic properties but estimates of activity differed according to whether they were obtained by determination of affinity constants on guinea-pig isolated ileum or production of mydriasis in mice. From measurements of affinity constant on the guinea-pig ileum it is concluded that BA compounds interact with only one muscarinic receptor. However, the high activity of the deca- and undecamethylene BA compounds in producing mydriasis suggest that these compounds possibly interact with two receptors at once.
The central hypotensive action of amphetamine, ephedrine, phentermine, chlorphentermine and fenfluramine
Authors: HOYER IRIS , VAN ZWIETEN P A 
Published: April 2011

Abstract
The influence of amphetamine, ephedrine, phentermine, chlorphentermine and fenfluramine on blood pressure after infusion into the vertebral artery was studied in anaesthetized cats. All drugs lowered blood pressure after infusion into the vertebral artery but showed hypertensive properties upon intravenous administration in the same dosage, although chlorphentermine (i.v.) decreased pressure after a minor initial rise. The hypotensive action of amphetamine was blocked by piperoxan or yohimbine (α-adrenoceptor blocking agents) and by haloperidol which is known to block central adrenoceptors. The hypotensive action of amphetamine was abolished in reserpinized cats and usually a small increase in blood pressure was observed in these animals after infusion of amphetamine in the vertebral artery. The hypotensive action of amphetamine is probably due to the mobilization of noradrenaline in the brain. The results suggest that the drugs show central hypotensive properties probably brought about by stimulation of central α-adrenoceptors, thus causing a decrease in peripheral sympathetic tone. This general principle would also explain the central hypotensive properties of α-methyl- dopa, α-methylnoradrenaline, l-dopa and m-tyrosine.
In vitro synthesis of noradrenaline in ganglia and salivary glands after in vivo preganglionic stimulation
Authors: CHIUEH C C , BHATNAGAR R K , MOORE K E 
Published: April 2011

Abstract
The extent of synthesis of [14C]noradrenaline from [14C]tyrosine and from [14C]dopamine was assessed in slices of superior cervical ganglia, representing cell bodies, and in submaxillary salivary glands, representing terminals of noradrenergic neurons of the cat. Immediately and 6 h after preganglionic stimulation for 3 h the rate of synthesis of noradrenaline from tyrosine and dopamine was not altered in ganglia. In salivary glands, however, synthesis of noradrenaline from both tyrosine and dopamine was increased at both times. These results suggest that acute periods of increased neural activity results in the acceleration of noradrenaline synthesis in the terminals but not in the cell bodies of noradrenergic neurons.
Binding of prostaglandin to human serum albumin
Authors: UNGER W G 
Published: April 2011

Abstract
The interaction of tritiated prostaglandin E1 (3H-PGE1) with various constituents of human blood was examined by equilibrium dialysis and incubation experiments. Plasma bound 3H-PGE1 weakly, apparently due to an interaction with serum albumin. Blood cells and plasma globulins did not interact with PG. When albumin and other proteins were precipitated by ethanol, as a preliminary stage of extracting PG from plasma, the recoveries of added PGs were poor. Addition of acid and non-precipitating amounts of ethanol (40–50%) to the plasma allowed quantitative extraction of added PGE, F, and A compounds into chloroform.
The effect of N-alkyl chain length and stereochemistry on the absorption, metabolism and urinary excretion of N-alkylamphetamines in man
Authors: Beckett A H , Shenoy E V B 
Published: April 2011

Abstract
Urinary excretion in man, of the unchanged drug and metabolite amphetamine, has been investigated after the (+)- and (-)-isomers of methyl-, ethyl-, n-propyl- and n-butyl- amphetamine had been taken by mouth under acidic urinary pH. The total metabolism of (+)-methyl-, ethyl-, and n-propyl-amphetamine was greater than that of the corresponding (-)-isomers but there was no difference in the total metabolism of the (+)- and (-)-n-butylamphetamine. A direct correlation was obtained for the (+)-but not the (-)-isomers between the partition coefficient of the compounds in an n-heptane/aqueous system, their buccal absorption and the total metabolism. The (+)-isomers of methyl- and ethyl-amphetamine were N-dealkylated more than their (-)-enantiomorphs but (-)-n-propylamphetamine was N-dealkylated more than the (+)-isomer.