bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.
Gas-liquid chromatographic estimation in blood of ICI 58 834
Authors: Case D E
Published: April 2011

The blood levels attained at therapeutic oral doses of ICI 58 834 hydrochloride, a novel psychotropic agent, are adequately assayed by gas-liquid chromatography. The free base is extracted into benzene and converted to its heptafluorobutyrate derivative. The derivative is chromatographed on a column of 1% XE60 on Gas-Chrom Q and detected by electron capture. Recovery from blood is 80–90% and the minimum detectable level is about 20 ng compound ml−1 whole blood.
An infrared study of the interaction between Aerosil-200 and polydimethylsiloxane (dimethicone-1000)
Authors: Buist G J , Burton J S , Elvidge J A
Published: April 2011

The individual hydrogen-bonds formed between Aerosil-200 and dibutyl ether are stronger than those formed between the Aerosil and dimethicone-1000 (PMS). Nevertheless, because there is multiple hydrogen-bonding to the PMS and because the molecules of this fit the Aerosil surface well, the total interaction is very strong.
The effects of phospholipase C on excitation-contraction coupling mechanisms in smooth muscle
Authors: Lodge S , Leach G D H
Published: April 2011

The technique of incubation with phospholipase C has been used as a means of investigating the role of phospholipids in the excitation-contraction coupling mechanisms of smooth muscle. The effects of this incubation procedure were observed upon the interactions of calcium with the contractile responses of the guinea-pig ileum longitudinal muscle preparation under a number of conditions. The reduction in the acetylcholine responses of both normal and potassium depolarized tissues after incubation was partially restored by a tenfold increase in the calcium concentration of the bathing medium. A faster rate of decline of contractile responses upon immersion in calcium-free solutions and a slower rate of restoration upon the reintroduction of calcium were seen in both normal and depolarized tissues. The relation between the external calcium concentration and the size of the contractile responses to a given stimulus was also changed. The size of the response to added calcium obtained in a potassium depolarized preparation was also reduced after phospholipase C incubation. These results and their implications are discussed.
The bronchoconstrictor action of the tetradecapeptide bombesin in the guinea-pig
Authors: Impicciatore M , Bertaccini G
Published: April 2011

The tetradecapeptide bombesin was found to exert a potent spasmogenic action on the bronchiolar muscle of the anaesthetized guinea-pig. The threshold bronchoconstrictor dose ranged between 50 and 200 ng kg−1. Other spasmogenic substances tested in the same experimental conditions, except physalaemin, were much less effective. Since antagonists of acetylcholine, histamine or 5-hydroxytryptamine did not inhibit the bronchoconstriction it is suggested that bombesin acts either by direct stimulation of the smooth muscle or by the prior release of other, as yet unidentified, spasmogenic substances.
Anti-inflammatory activity in human plasma
Authors: Ford-Hutchinson A W , Insley M Y , Elliott P N C , Sturgess E A , Smith M J H
Published: April 2011

Pooled human plasma contains a fraction, separable by ultrafiltration and column chromatography, which possesses anti-inflammatory activity in the carrageenan oedema test in the rat, may be partially purified by solvent extraction, has an apparent molecular weight below 1000, and is resistant to acid and proteolytic digestion.

A substance showing experimental anti-inflammatory activity has been isolated from human serum (McArthur, Smith & Freeman, 1972). The present paper describes a much simpler preparation of this material from pooled human plasma, its partial purification by extraction with acetone and ethanol, its ultrafiltration through several membranes, and its resistance to acidic, proteolytic and thermal degradation. A preliminary account of part of this work has been published (Elliott, Ford-Hutchinson & others, 1973).
Stereochemical and structural assignment to benzomorphans by mass spectrometry
Authors: Vaughan D P , Beckett A H
Published: April 2011

The fragmentation of some alkyl-substituted-6,7-benzomorphans upon electron impact (70eV) is characteristic. The relative intensities of some ions varies in a predictable manner depending on the configuration of the C-9 hydrogen atom. Configuration and structure of 5,9-disubstituted-6,7-benzomorphans can be assigned by mass spectrometry even when only one isomer of a structure capable of existing in diastereoisomeric forms is available.
The use of radioisotopically labelled methyl esters in the determination of the 15-epimer content of prostaglandins
Authors: Jones M F
Published: April 2011

The quantitative determination of the 15-epimer content of prostaglandins by formation of their isotopically-labelled methyl esters is described. Either [3H]dimethyl sulphate or [14C]diazomethane are used as esterification reagents. The reaction products are separated by thin layer chromatography and the epimer ratio determined by scintillation counting of the labelled ester zones. The accuracy of the technique is illustrated by the determination of 15-epimer in ICI 74 205, a close analogue of PGF2α. Evidence for the uncatalysed reaction of diazomethane with the alcoholic hydroxyl groups of prostaglandin molecules, which could be significant in other prostaglandin analysis techniques (e.g. g.l.c.) which depend on quantitative esterification with this reagent, is also presented.
Studies on the nature of the increased monoamine oxidase activity in the rat heart after adrenalectomy
Authors: Callingham B A , Laverty R
Published: April 2011

The increased activity, induced by adrenalectomy, of the enzyme monoamine oxidase (MAO) in the rat heart was found to resemble closely that present in the hearts of control animals. No significant differences were observed in the nature of the response to heat denaturation, changes in pH or to inhibition by pargyline or clorgyline. The relative activities using the substrates tyramine, 5-hydroxytryptamine, dopamine or benzylamine were the same. No evidence was found to suggest the presence of a heat-stable or dialysable inhibitor of enzyme activity. In young rats there was an increase in the relative enzyme activity using benzylamine as substrate, compared with the activity using tyramine, in the first few days after adrenalectomy. No effect of adrenalectomy could be detected upon the MAO activity in the rat brain or liver. It is concluded that the increase in rat heart MAO following adrenalectomy cannot be due to the synthesis of an enzyme with different catalytic properties, nor to the transformation of the existing enzyme into one of increased catalytic ability but with different properties.
Chemical composition and potential activity of Argentine marihuana
Authors: Chiesa E P , Rondina R V D , Coussio J D
Published: April 2011

The occurrence and amount of Δ1-tetrahydrocannabinol, cannabidiol and cannabinol in Argentine marihuana have been investigated, and its potential activity assessed. The analytical method was applied to thirteen different samples obtained from the Argentine Police or from domestic cultivations of Cannabis sativa L. The Δ1-tetrahydrocannabinol content including decarboxylated precursors ranged from 0.1 to 8.3 g per 100 g of the dried drug according to the source.
Kinetics of three structurally related bicyclic antidepressant compounds—a comparison in the dog
Authors: Overø K Fredricson
Published: April 2011

Kinetic experiments have been made with three structurally related compounds selected from a series of bicyclic antidepressant compounds. Plasma concentrations were assayed after doses of 5 mg kg−1 given as an intravenous infusion over 2 h to three dogs. The data were evaluated according to a two compartment open model, and kinetic parameters reflecting distribution and elimination characteristics of the drugs were calculated. An attempt was made to evaluate possible relations between chemical structure and these parameters. The lowest drug levels and the most rapid elimination were obtained with a compound utilizing sulphoxidation as an additional pathway of metabolism. The compounds lacking this possibility had considerably slower elimination kinetics, the less lipophilic being the slowest one. Little individual variation was seen. A relation between increased lipophilicity and increased localization in the peripheral compartment was indicated. However, the importance of other factors, such as binding phenomena within tissues, was also indicated.
The binding of paracetamol to plasma proteins of man and pig
Authors: Gazzard B G , Ford-Hutchinson A W , Smith M J H , Williams R
Published: April 2011

The binding of N-acetyl-4-aminophenol (paracetamol) to human and porcine plasma at both toxic and therapeutic concentrations was investigated by ultrafiltration and equilibrium dialysis over the range 50–300 μg ml−1. Plasma protein binding occurred at paracetamol concentrations greater than 60 μg ml−1. The extent of protein binding at a plasma concentration of 280 μg ml−1 of the drug is between 15 and 21% for both pig and man. There is no appreciable binding to erythrocytes in either species over the whole concentration range studied.
Dissolution and bioavailability of digoxin tablets
Authors: Fraser E J , Leach R H , Poston J W , Bold A M , Culank L S , Lipede A B
Published: April 2011

A dissolution test is described for tablets of digoxin B.P. Dissolution profiles are reported for 11 brands of digoxin tablets available in Gt. Britain in 1972. Good correlations exist between both the area under the serum concentration/time curve from 0–6 h and (1) the amount of digoxin dissolved in 1 h, (2) the reciprocal of the time for 50% dissolution.
Determination of the thermodynamics of hydroxyl and carboxyl groups in solutions of drug molecules
Authors: Davis S S
Published: April 2011

The contributions of hydroxyl and carboxyl groups to solute activity and partition coefficients have been investigated using literature data. Both polar functions give rise to a reduced activity coefficient for aromatic solutes in water and differences exist between ring and asubstitution. Partition coefficients are similarly affected but the magnitude of the group contribution to the free energy of transfer is dependent on the nature of the solute and the organic partition solvent. The contribution for the groups in the terminal position in aliphatic compounds can be obtained by an extrapolation procedure where the group value is a composite of the polar function and a term that takes into account the inequality of aliphatic CH2 and CH3 groupings (H. .OH, H. .COOH). For a range of solvents there is good correlation between hydroxyl and carboxyl group values. In addition an attempt has been made to correlate group values for CH2, CH3, H. .OH, H. .COOH, with physico-chemical parameters that are characteristic of the partition system. The best correlations are obtained between group values and the solubility of water in the organic partition solvent. The H. .OH and H. .COOH group values can also be correlated with infrared spectroscopy data and self-association constants respectively.
A note on the chemical change of pentazocine in aqueous acidic media
Authors: Vaughan D P , Beckett A H
Published: April 2011

Pentazocine decomposes in the acidic conditions used to hydrolyse glucuronides. The structure of the decomposition product was identified as 2′-hydroxy-2-(3-methyl-3-hydroxy-butyl)-5,9-dimethyl-6,7-benzomorphan. Pentazocine is stable when incubated at 37°, pH 5.0, and can be stored in biological fluids without drug loss.
Factors affecting the antidiuretic actions of the 18-monoacetate of (+)-aldosterone and of a substance secreted by heart muscle, in rats
Authors: Lockett Mary F
Published: April 2011

The method for the assay of a steroid-like substance secreted by the heart (HS) in terms of the biological activity of the 18-monoacetate of (+)-aldosterone (18MA) has been improved. Rats were equipped with ascending carotid, descending external jugular and bladder polyethylene cannulae and the urethra was ligated, under pentobarbitone anaesthesia, 24–36 h before use. Assays were made in restrained animals during sustained water diuresis induced by an intravenous infusion of glucose, 5%, and NaCl, 0ṁ9%; 2: 1 at 9 mlh−1. Antidiuretic responses (measured as the area under the curve) to ascending carotid injections of 18MA and of HS, made at 0ṁ01 ml s−1, maximum 15 s, were obtained from single dilutions of HS and 18MA: urine flow per min was recorded from drop (0ṁ025 ml) counters. Denervation of the carotid sinus above the carotid cannula did not influence the antidiureses. Data obtained were analysed by normal statistical procedures. Ascending carotid injections of 18MA and HS did not influence mean systemic arterial pressures, the clearances of creatinine and of PAH or the urinary outputs of Na+ and K+. The antidiuresis produced was compatible with the release of ADH by HS and by 18MA. Marked seasonal variations in threshold sensitivity to 18MA and in the slopes of the log dose-effect curves for the antidiuretic actions of 18MA are described. Variations both in the threshold sensitivity and in the log dose-effect curves for the anti-diuresis caused by 18MA occur between rats of different strains.
A note on the effect of amantadine on body temperature in mice
Authors: Davies J A , Redfern P H
Published: April 2011

Amantadine hydrochloride caused a dose-dependent fall in rectal temperature in mice. This response was antagonized by haloperidol, which itself produced some hypothermia, and by pretreatment with α-methyl-p-tyrosine. The mode of action of amantadine and the possible involvement of dopamine in the control of body temperature is discussed.
The determination of fluorochlorocarbons in air and body fluids
Authors: Rauws A G , Olling M , Wibowo A E
Published: April 2011

A gas chromatographic method for the separation and determination of fluorochlorocarbons (FCC's) is described. Porapak Q is used as the solid phase. The column temperature is 150°. The compounds are detected by means of a tritium foil electron capture detector. The retention times under the conditions used are 1, 2, 4 and 7ṁ5 min for the FCC's 11, 114, 12 and 113 respectively. Concentrations in air are determined directly, the concentrations in body fluids are determined by means of head space analysis. The detection limits for the various FCC's vary between 0ṁ5 and 35 pg. The method is applied in determining FCC concentrations in air and in rat blood in vivo.
Some properties of an oil-soluble phosphated fatty alcohol ethoxylate
Authors: Groves M J , Mustafa R M A , Carless J E
Published: April 2011

Although phosphated hydrocarbon ethoxylates are claimed to have properties associated with the presence of both non-ionic and anionic groups in their molecules, a recent investigation of a phosphated nonylphenol ethoxylate demonstrated that the phosphate group had only a slight influence on the properties of this compound. The properties of an oil-soluble phosphated fatty alcohol ethoxylate of commercial origin has now been investigated. This material was substantially homogeneous, corresponding to a structure C9H19-(OCH2CH2)3-O-PO(OH)2—mol wt = 356

Although with considerable solubility in non-polar solvents, the compound has a slight solubility in water which is increased with increased pH, suggesting that the polar phosphate group has an influence on the properties of the compound. Measurement of the surface tension of aqueous solutions over a temperature range of 20–50° showed that there was an inflection point in the relation between cmc and temperature, behaviour typical of an anionic surfactant. As the pH is increased, the interfacial cross-sectional area of the molecule is progressively reduced at the air-water interface, but increased at the hexane-water interface. These results are discussed in terms of the orientation of the molecule at the interface, and the influence of a charged polar head group.
The interaction of Escherichia coli and magnesium trisilicate in aqueous suspension
Authors: Beveridge E G , Todd Kathleen
Published: April 2011

E. coli interacted strongly with magnesium trisilicate particles in buffer solution with aggregation of the particles and ready removal of bacteria from suspension, an equilibrium being attained between adhering and unattached cells. The relation between log10 (uptake bacteria g−1 magnesium trisilicate) and log10 (equilibrium concentration bacteria cm−3) suggested some analogy to the Langmuir type adsorption of solutes. Since both bacteria and particles possessed moderate negative electrical charges of similar magnitude, their interaction is thought to be due to long range additive Van der Waals forces rather than by electrostatic attraction.
Effects of adrenalectomy and of hypophysectomy on the development of sound-withdrawal hypertension
Authors: Marwood J F , Ilett K F , Lockett Mary F
Published: April 2011

Female rats, initially 160–180 g, of a single inbred Wistar strain develop an hypertension reaching peak value at 4 weeks and stabilizing at a slightly lower level by the 6th week after transfer to a sound-proof semi-anechoic room (SPR). Blood corticosterone and deoxycorticosterone levels do not change significantly: urinary catecholamine excretion gradually decreases, and the rates of the urinary excretion of water and of Na+ in the first hour of water diuresis are depressed throughout the first week in the SPR. Adrenalectomy with salt maintenance, and hypophysectomy, prevent the development of this hypertension. Treatment with methyl prednisolone restores the ability of the adrenalectomized, but not of the hypophysectomized, rats to develop sound-withdrawal hypertension.
Metabolism and excretion of diethylpropion in man under acidic urine conditions
Authors: Testa B , Beckett A H
Published: April 2011

After oral administration, diethylpropion is rapidly and extensively metabolized in man by N-de-ethylation and stereoselective carbonyl reduction. The unchanged drug excreted in acidic urine represents about 2% of the dose, while the total metabolites determined account for some 85%. The excretion curves indicate that the probable contribution of the parent compound to the observed activity is small. The major metabolites, together representing about 70% of the dose, are N-ethylaminopropiophenone, (+)-N-diethylnorpseudoephedrine, (+)-N-ethylnorpseudoephedrine, (-)-norephedrine and (-)-norpseudoephedrine. The other stereoisomers of the three amino-alcohols, and aminopropiophenone, are present in minor amounts.
Competitive binding of two drugs for a single binding site on albumin: a circular dichroic study
Authors: Perrin J H , Nelson D A
Published: April 2011

Sulphaethidole has been previously shown to have two classes of binding site on bovine serum albumin (BSA). Only the primary binding site is capable of inducing optical activity in the drug. Drugs that bind to the same primary binding site as sulphaethidole, but do not become optically active themselves on binding, reduce the size of the circular dichroism signal in competitive binding studies with sulphaethidole. The binding constant for such antagonists can be calculated. It appears that a range of acidic drugs share the same primary binding site on bovine serum albumin; basic drugs do not compete for this site.
Adsorption of benzoic acid on sulphadimidine: suppressive effect of some hydrophilic polymers
Authors: Khalil Saleh A H , Nasipuri R N
Published: April 2011

The uptake of benzoic acid on sulphadimidine particles has been investigated. Depending on the concentration of sulphadimidine in the system, benzoic acid was adsorbed to the extent of 94%. Data from the adsorption experiments were shown to fit a Langmuir plot for systems containing up to 0.2 g 100 ml−1 sulphadimidine. The suppressive effect of three hydrophilic polymers on adsorption was studied; the results followed the sequence: Polyvinylpyrrolidone (PVP) > methylcellulose > sodium carboxymethylcellulose. Dialysis experiments revealed that, within the range of concentrations used, neither PVP nor methylcellulose was significantly bound to benzoic acid.
The extraction and estimation of the cannabinoids in Cannabis sativa L. and its products
Authors: Fairbairn J W , Liebmann J A
Published: April 2011

A convenient method for the complete extraction of the cannabinoids from fresh plant material, herbal cannabis, cannabis resin and reefers, has been devised. Chloroform was a more suitable solvent than light petroleum or ethanol and simple shaking of powdered material with the solvent was effective. Fresh material should be air-dried and powdered before extraction. The main cannabinoids in the extract are determined by g.l.c. using androst-4-ene-3,17-dione as internal standard. The coefficient of variation for repeated determinations of THC on a single extract was 1.4%; for all operations, including sampling and extraction, it was 2.7%. Duplicate analyses of 24 samples of herbal cannabis and of 20 reefers, all of varying potency, showed that the errors fell within the expected limits for THC, CBD and CBN. The method is simple and rapid; duplicate determinations can be completed in about 2 1/2 h.
Steryl esters of Digitalis purpurea L. herb
Authors: Evans F J
Published: April 2011

The non-polar fraction sterols of Digitalis purpurea flowering plants were separated into a steryl ester and free sterol fraction. The ester fraction consisted of cycloeucalenol, obtusifoliol, 24-methylenelophenol, 24-ethylenelophenol, cholesterol, campesterol, stigmasterol, sitosterol, isofucosterol and 24-methylenecholesterol. These compounds were esterified with an αβ-unsaturated C10 fatty acid, whereas the glycerides from the same plant consisted of a complex of acids predominated by C18 and C16 types. The free sterols consisted of cycloartenol, 24-methylenecycloartenol, cholesterol, campesterol, stigmasterol, sitosterol, fucosterol and 24-methylenecholesterol. The relative proportions of each of these steroids in the two fractions were recorded.
The oxidation of 6-hydroxydopamine
Authors: Powell W S , Heacock R A
Published: April 2011

The oxidation of 6-hydroxydopamine (I) with molecular oxygen or potassium ferricyanide in aqueous solution has been shown to lead mainly to the formation of the uncyclized quinone 2-(β-aminoethyl)-5-hydroxy-p-benzoquinone (VII). However this quinone cyclized slowly, presumably to norepinochrome (i.e. indoline-5,6-quinone, XII), since 5,6-dihydroxyindole (II), known to be readily formed by rearrangement of norepinochrome (XII), can be isolated from these solutions. 5,6-Dihydroxyindolines (cf. XIII) can also be isolated (as their acetyl derivatives) from the products obtained by the addition of reducing agents to solutions containing 6-hydroxydopamine oxidation products. No evidence was found to suggest that the possible alternative cyclization of the quinone VII to the p-quinonoid aminochrome 6-hydroxyindoline-4,7-quinone (III) occurred to any significant extent.
Analysis of the effects of apomorphine and bulbocapnine in relation to the proposed dopamine receptor
Authors: Patil P N , Burkman A M , Yamauchi D , Hetey S
Published: April 2011

On rat isolated vas deferens, apomorphine was found to be l/5th as active as dopamine. Reserpine or cocaine pretreatment failed to reduce the response to apomorphine. Low concentrations of apomorphine which do not cause contraction of the tissue, antagonize the effects of dopamine. The effects of dopamine were antagonized equally by phentolamine or apomorphine. On rabbit aortic strips 4 × 10−4M apomorphine repeated at 45 min intervals induces pronounced tachyphylaxis. During the tachyphylactic period dopamine was not inhibited to a significantly greater extent than was phenylephrine. Bulbocapnine tested against dopamine and phenylephrine yielded identical pA2 values of 6. Only at 10−5M was bulbocapnine observed to produce a preferentially greater blockade of dopamine. Dopamine or isoprenaline-induced relaxations of aortic strips were not blocked by bulbocapnine. Dopamine and 3 times 10−6M bulbocapnine increased the chronotropic effects in atria. Apomorphine and higher doses of bulbocapnine produced rate decelerating effects. On atria low doses of apomorphine were equally effective in reducing the effects of dopamine or histamine. These results are discussed in light of the proposal that the effects of apomorphine and bulbocapnine involve dopamine receptor interactions. In all three tissues there was no clear cut evidence of specific dopamine receptors.
Polyphloretin phosphate temporarily potentiates prostaglandin E2 on the rat fundus, probably by inhibiting PG15-hydroxydehydrogenase
Authors: Ganesan P Adaikan , Karim S M M
Published: April 2011

Polyphloretin phosphate (PPP), an antagonist of some smooth muscle action of prostaglandins, potentiates the effect of prostaglandin E2 on the rat isolated stomach fundus preparation. No such potentiation could be demonstrated for prostaglandin 15(S) 15 methyl E2 methyl ester, a synthetic analogue of prostaglandin E2. PPP also stimulates the longitudinal muscle of human isolated jejunum to contract. Evidence is produced to show that the potentiation of prostaglandin E2 and the direct stimulant action of PPP are due to inhibition of prostaglandin 15-OH dehydrogenase, an enzyme which inactivates prostaglandin E2 but not 15(S) 15 methyl E2 methyl ester.
Spectrophotometric determination of microgram quantities of acetylsalicylic anhydride in acetylsalicylic acid
Authors: Bundgaard Hans , Bundgaard Charlotte
Published: April 2011

A rapid and convenient method for the determination of an immunogenic impurity in acetylsalicylic acid, acetylsalicylic anhydride, is described. The method is based on the spectrophotometric measurement at 362 nm of 4-benzylidene-2-phenyloxazolin-5-one, formed in quantitative yield by allowing acetylsalicylic anhydride, pre-extracted from the acetylsalicylic acid by a benzene-aqueous phosphate buffer system, to react with a mixture of pyridine and sodium α-benzamido-cinnamate in ethanol for 30 min at 20°. The method is reproducible and permits determination of 0ṁ0005% of acetylsalicylic anhydride in acetylsalicylic acid. Applying the method to nine different commercial acetylsalicylic acid preparations, acetylsalicylic anhydride was found to be present in amounts ranging from 0ṁ0012 to 0ṁ024%.
Quantitative determination of imipramine and desipramine in human blood plasma by direct densitometry of thin-layer chromatograms
Authors: Nagy Adam , Treiber Laszlo
Published: April 2011

Imipramine and desipramine have been estimated in the plasma of patients receiving therapeutic doses of imipramine. The compounds were extracted as bases into n-heptane, separated by thin-layer chromatography and transferred into coloured spots by an oxidative procedure. The quantification was made with a new densitometric technique of high sensitivity. The coefficient of variation was 11–16% at concentrations of 20 μg litre−1 (71ṁ2 nmol and 75ṁ0 nmol litre−1 for imipramine and desipramine respectively) and the recovery was 70–81%.
Imipramine and its metabolites in human brain
Authors: Christiansen Johs , Gram Lars F
Published: April 2011

A quantitative and qualitative thin-layer chromatographic study of the distribution of imipramine and its metabolites in 13 different regions of the brain in a fatal case of intoxication has been made. A quantitative thin-layer chromatographic method for in situ determination of imipramine and desipramine has been developed. The concentration of imipramine ranged from 4–36 μg g−1 and of desipramine from 0–8 μg g−1 in different parts of the brain. 8 identified and 8 unidentified metabolites were detected in the different parts of the brain. Among the identified were hydroxy-, N-oxide, and iminodibenzyl-metabolites. The metabolic pattern found corresponds closely to the pattern found in human heart tissue and in urine from patients given imipramine.
Design of agents for stimulation of neostriatal dopaminergic mechanisms
Authors: Costall B , Naylor R J , Pinder R M
Published: April 2011

The structure-activity requirements for stimulation of striatal dopaminergic mechanisms were investigated using a series of phenethylamine derivatives, apomorphine and isoapomorphine, and the intracerebral injection technique for direct application into the striatum. Asymmetric body posturing (unilateral injections in saline-and haloperidol-pretreated rats) and hyperactive/stereotyped be-behaviour (bilateral injections in nialamide-pretreated rats) were used as indices of dopaminergic stimulation. Of 24 phenethylamine derivatives studied, 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) possessed maximum activity. Alteration in length of the ethylamine side-chain, substitution of the α-C atom (α-methyldopamine) or hydroxylation of ß-C atom (noradrenaline) markedly reduced or abolished activity. Activity was also decreased by N-methyl substitution but epinine was active. The catechol moiety appeared essential for dopaminergic stimulation since the 3- or 4-hydroxyphenethylamines (tyramine, m-tyramine) were inactive and 2-(3,4-methylenedioxyphenyl)ethylamine was only weakly active. The marked dopamine-like activity of the 2-(3,4-diacetoxyphenyl)ethylamine compounds was attributed to their non-enzymic hydrolysis to dopamine in situ. The stereoselectivity of the dopamine-induced effects was assessed using trans and cis-2-(3,4-methylenedioxyphenyl)cyclopropylamine. The trans conformer was active and the importance of this conformation was further indicated by the inactivity of isoapomorphine compared with apomorphine. It is suggested that the results provide a rational basis for the design of drugs required to stimulate striatal dopamine receptors and that the intrastriatal injection technique may be useful in the detection of potential antiparkinson agents.
Interaction of phenobarbitone and ethanol in mice studied from dose-response curves and drug concentrations in blood
Authors: Curry Stephen H , Scales Alistair H
Published: April 2011

The interaction of phenobarbitone and ethanol given intraperitoneally to mice has been studied. Dose-response relations were established for incidence of death, sleeping time and time of onset of sleep. Concentrations of phenobarbitone and ethanol were assayed in whole blood samples. When the two drugs were administered together, sleep occurred more rapidly than calculated as likely on the basis of the effects of the drugs given individually. On the other hand, sleep was of shorter duration and the incidence of death was less than anticipated. These modifications of the expected effects related to drug concentration changes in blood. Isobolograms indicated the need for precision in describing the interactions as potentiation, addition or antagonism, as different terms could be applied depending on the effect measured.
Effect of butriptyline on the brain uptake mechanisms for noradrenaline and 5-hydroxytryptamine
Authors: Pugsley T A , Lippmann W
Published: April 2011

Butriptyline, a tricyclic compound (40 mg kg−1, i.p.), in contrast to the tricyclic desipramine (20 mg kg−1, i.p.), did not alter the accumulation or metabolism in areas of the rat brain of intraventricularly-injected [3H]noradrenaline. It did not appreciably inhibit the displacement of 5-HT by α-ethyl-3-hydroxy-4-methyl phenethylamine in comparison with the tricyclic chlorimipramine. Butriptyline potentiated central 5-HTP effects only slightly whereas chlorimipramine displayed a strong potentiation. It is concluded that butriptyline differs significantly from desipramine, as no inhibitory effect on brain noradrenaline uptake was found, and from chlorimipramine, as only a weak inhibitory activity on brain 5-HT uptake was observed.
Improved parameter estimates in drug-protein binding studies by non-linear regression
Authors: Madsen B W , Robertson J S
Published: April 2011

A quantitative comparison of various methods of fundamental binding parameter estimation is presented. For optimal reliability, choice of a particular approach should be made on a critical assessment of the experimental procedure and various calculated statistical criteria, rather than on the ease of data treatment.