bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of the length of the stimulus period and frequency of sympathetic stimulation on the response of the guinea-pig isolated vas deferens to bretylium, guanethidine and amphetamine
Authors: Day M D
Published: April 2011

The height of contraction of guinea-pig isolated vas deferens preparations in response to pre- or postganglionic sympathetic nerve stimulation at various stimulus frequencies was shown to vary with varying length of stimulation period. Short stimulation periods, as used by some workers, produced suboptimal contractions especially at the lower frequencies. It is suggested that variations in the length of the stimulation period could account for some of the contradictory results reported by various workers using this preparation. Thus the effect of low concentrations of dexamphetamine was qualitatively changed as the length of the stimulation period was increased; with short stimulation periods dexamphetamine impaired the responses to sympathetic stimulation but enhanced them if stimulation was continued until contractions had reached the maximum height obtainable. Higher concentrations of dexamphetamine impaired the contractions, the effect being most marked against the higher stimulus frequencies. Using stimulation to maximal effect a qualitative difference in the blocking actions of bretylium and guanethidine was demonstrated. Bretylium reduced the responses to the higher stimulus frequencies to a greater extent than it reduced the responses to the lower frequencies. Guanethidine reduced the responses to all frequencies so that there was a parallel shift of the frequency/response curve to the right. The possible significance of these findings is discussed.
Effect of some spasmolytic drugs on the isolated human myometrium
Authors: Lehrer D N
Published: April 2011

Spasmolytic drugs possessing a musculotropic action appear to be the most effective in inhibiting the motility of the human myometrium in vitro. Substances whose action is mediated via a predominently β-receptor mechanism have relatively little or no effect on this preparation.
Protein binding and the excretion of some azo dyes in rat bile
Authors: PRIESTLY B G , O'REILLY W J
Published: April 2011

The kinetics of biliary excretion of four dyes, amaranth, geranine, lissamine and dechlorolissamine have been examined in the rat. The protein binding of each dye to blood and liver in vitro was examined, and a correlation found between excretion rate and the relative degree of binding of dye to the liver compared with the blood.
Effect of solubilisation on the antibacterial activity of hexachlorophane
Authors: Anderson R A , Morgan K J
Published: April 2011

The solubilisation of hexachlorophane by various non-ionic agents has been studied at pH 2·5 and 8·0. The interaction of the phenol with these agents in unsaturated systems at pH 8·0 has been determined by a dialysis technique using rubber latex membranes. The bactericidal activity is shown to depend on the concentration of unbound hexachlorophane, but this is not simply related to the degree of saturation of the total system. The results of agar-plate diffusion tests cannot be correlated with either the concentration of unbound hexachlorophane or the total concentration.
Accumulation of α-methyltyramine by the noradrenaline uptake process in the isolated rat heart
Authors: IVERSEN LESLIE L
Published: April 2011

In the perfused isolated rat heart 3H-α-methyltyramine is accumulated as rapidly as noradrenaline. The accumulation of 3H-α-methyltyramine is reduced by the presence of noradrenaline or other drugs known to inhibit the noradrenaline uptake mechanism. 3H-α-Methyltyramine and noradrenaline probably compete for a common uptake mechanism. In these experiments less than 5% of the 3H-α-methyltyramine accumulated by the heart was metabolised to α-methyloctopamine.
The preparation of some derivatives of glycyrrhetic acid and oleanolic acid
Authors: DEAN P D G , HALSALL T G , WHITEHOUSE M W
Published: April 2011

Some new derivatives of glycyrrhetic acid and oleanolic acid were prepared and characterized. Various combinations of the modified and normal functional groups were synthesized as required for a separate study of the uncoupling activities of glycyrrhetic acid and oleanolic acid. The hydroxyl functions of these two acids were modified to β-carboxypropionyl, acetyl and β-methoxycarbonylpropionyl esters. The carboxyl function of glycyrrhetic acid was converted to amide, p-amidobenzoic acid, o-amidobenzoic acid and the glycine conjugate of the acid. 11-Deoxy (glycyrrhetic acid) and 9,11-dehydro-11-deoxo (from both acids) analogues were prepared. 11-Oxo analogues of oleanolic acid were synthesized as well as the methyl esters.
The effect of succinylcholine on the isolated retractor bulbi muscle of the cat
Authors: BACH-Y-RITA PAUL , LEVY JOSEPH V , STEINACKER ANTOINETTE
Published: April 2011

The retractor bulbi muscle of the cat does not contain multi-innervated slow fibres, and succinylcholine (suxamethonium), 1–1000 μg/ml, causes no contracture of the isolated muscle. However, succinylcholine in a concentration of 1 μg/ml causes a contracture of the isolated inferior oblique and rectus muscles of the cat eye.
Modification of morphine analgesia by drugs affecting adrenergic and tryptaminergic mechanisms
Authors: Fennessy M R , Lee J R
Published: April 2011

The effects of drugs that modify adrenergic or tryptaminergic mechanisms were tested on the analgesic action of morphine in mice. Analgesia was assessed by the hot plate method and phenylquinonewrithing method. Reserpine antagonized the analgesic action of morphine in both tests, the maximal effects occurring 6–8 h after the administration of reserpine. p-Chlorophenylalanine antagonized the analgesic action of morphine as assessed by the writhing method but not by the hot plate method. The analgesic action of morphine was not modified in either test by pretreatment with α-methyl-p-tyrosine, propranolol, phentolamine or methysergide. These results suggest that the analgesic action of morphine, as measured in the writhing test, may be mediated by 5-hydroxytryptamine but that other mechanisms may be involved in the hot plate test.
Decreased distribution of oxotremorine to brain after pharmacological blockade of its peripheral acetylcholine-like effects
Authors: KARLÉN BO , TRÄSKMAN LIL , SJÖQVIST FOLKE
Published: April 2011

The distribution of [3H]oxotremorine, after intravenous injection, to brain and tissues of rats and mice has been studied. In rats, oxotremorine (0·3 mg/kg) rapidly reached the brain with a peak concentration of 1200 ng/g at 1 min. Blockade of the peripheral muscarinic effects of oxotremorine with amitriptyline methyl iodide or atropine methyl nitrate (25 mg/kg, s.c.) markedly decreased the brain content of oxotremorine (peak concentration 400 ng/g), probably as a result of its more rapid distribution to peripheral tissues and an increased volume of distribution. The ratio of drug distribution between plasma and brain is unaffected by pretreatment with anticholinoceptive drugs. Also, the total body concentrations of oxotremorine are similar in pretreated rats and controls. A small dose of oxotremorine (10 μg/kg) is distributed similarly in pretreated rats (amitriptyline methyl iodide, 25 mg/kg, s.c.) and in controls. In mice there was a linear relation between dose, up to 180 μg/kg, and brain concentration of oxotremorine. At higher doses, relatively; more drug reached the brain. Oxotremorine induced a marked fall in blood pressure in the unanaesthetized rat that was reduced by amitriptyline methyl iodide and reversed by atropine methyl nitrate. It seems likely that differences in blood flow between pretreated rats and controls are responsible for the differences in the distribution of the drug.
A method for the continuous recording of peripheral vascular conductance
Authors: GARDINER D G , HAMILTON T C , PARKES M W
Published: April 2011

A method is described for the continuous recording of the conductance of a perfused vascular bed, derived from simultaneous measurement of blood flow and perfusion pressure. For the autoperfused hindquarters of the anaesthetized cat, it is shown that for vasoconstrictor or vasodilator drugs, injected either intravenously or into the arterial perfusion circuit, a record of changes in conductance may be of considerable aid in clarifying the responses of the vessels.
The quantitative analysis of polyvinylpyrrolidone by infrared spectrophotometry
Authors: RIDGWAY K , RUBINSTEIN M H
Published: April 2011

The quantitative assay of the binding agent polyvinylpyrrolidone (PVP) in granules of magnesium carbonate has been shown to be possible. The method is to determine the infrared absorption spectrum of a chloroform extract. Quantities of PVP down to 0·1 mg can be successfully assayed to ±1 % in solution as dilute as 0·1 % w/v.
Correlation of the recovery of the granular uptake-storage mechanism and the nerve impulse induced release of [3H]noradrenaline after reserpine
Authors: ALMGREN O , LUNDBORG P
Published: April 2011

Rats were treated intraperitoneally with 10 mg/kg reserpine. After various time intervals 1 μg/kg ± [3H]noradrenaline (3H-NA) was administered intravenously, and the uptake into subcellular fractions of the submaxillary gland was measured or, in some of the rats, the sympathetic chain of the neck was electrically stimulated with 10 impulses/s for 30 min. The release of 3H-NA and the contraction response of the lower eye-lid were measured. A striking parallel was observed between the recovery of the 3H-NA uptake into the amine storage particles and the nerve impulse-induced release of 3H-NA, and also the recovery of the functional response. The somewhat earlier recovery of the 3H-NA uptake into the coarse fraction might reflect the existence of another type of amine storage granule or might represent granules present near the nerve cell membrane. A possible increase in the turnover of the adrenergic transmitter during the period of recovery after reserpine is discussed.
The effects of sympathetic nerve stimulation and guanethidine on parasympathetic neuroeffector transmission; the inhibition of acetylcholine release
Authors: VIZI E S , KNOLL J
Published: April 2011

The effect of noradrenaline released either by sympathetic nerve stimulation or guanethidine added to the organ bath has been studied on acetylcholine release from parasympathetic nerve terminals and compared with the effect of exogenous noradrenaline. Sympathetic nerve stimulation, guanethidine and noradrenaline reduced the release of acetylcholine from resting rabbit intestine by up to 70%. Sympathetic stimulation and guanethidine failed to reduce acetylcholine release in preparations previously depleted of noradrenaline. Noradrenaline added to the bath still remained effective. The fact that noradrenaline released is capable of inhibiting acetylcholine release supports the concept that noradrenaline physiologically controls the release of acetylcholine.
Myocardial necroses produced by intravenous infusion of isoprenaline into rats
Authors: GRYGLEWSKI R J , KULIG A , KOSTKA-TRABKA E
Published: April 2011

Intravenous infusion of isoprenaline in doses of 2,20,200,2000 μg/kg per min over 20 min into heparinized Wistar rats results in myocardial necroses and a rise in SGPT activity, erythrocyte sedimentation rate and leucocytosis. A quantitative method for estimation of intensity and distribution of myocardial necrotic foci is described. The intensity of myocardial lesions is observed linearly related to the infused isoprenaline at 2, 20 and 200 μg/kg per min. Damaged areas are mainly found in subendocardial and apical regions of left ventricle.
Some effects of caffeine and aminophylline on the turnover of catecholamines in the brain
Authors: WALDECK BERTIL
Published: April 2011

The effect of caffeine and aminophylline on the turnover of noradrenaline and dopamine in the mouse brain was studied by two different methods: estimation of the rate of disappearance of the transmitter after inhibition of synthesis and measurement of the accumulation of [3H]noradrenaline (3H-NA) and [3H]dopamine (3H-DA) after administration of [3H]tyrosine. After inhibition of the tyrosine hydroxylase the xanthines had little or no effect on the disappearance of both catecholamines. After inhibition of dopamine β-hydroxylase, both xanthines increased the rate of disappearance of noradrenaline. When given in sufficiently large doses both xanthines increased the yield of 3H-NA and 3H-DA from [3H]tyrosine. Pretreatment with a monoamine oxidase inhibitor caused a decrease in the yield of the tritiated catecholamines, which could be counteracted by the xanthines. Stimulation of the noradrenaline receptors by clonidine appeared to cause a decrease in the yield of 3H-NA and an increase in the amount of 3H-DA formed from [3H]tyrosine. Conversely, stimulation of the dopamine receptors by apomorphine caused a decrease in the yield of 3H-DA and an increase in that of 3H-NA. Also, in caffeine-treated animals, clonidine and apomorphine decreased the yield of 3H-NA and 3H-DA respectively. However clonidine could not increase 3H-DA concentrations, nor apomorphine the 3H-NA concentrations more than did caffeine alone. Thus, caffeine and aminophylline appear to increase the rate of turnover of both catecholamines in the brain.
Structural influences upon antihistamine activity; 3-amino-1-aryl-1-(2-pyridyl)propenes and related compounds
Authors: ISON R R , CASY A F
Published: April 2011

A series of 3-amino-1-aryl-1-(2-pyridyl)propenes and related compounds have been prepared by the dehydration of corresponding tertiary alcohols, and the configurations of geometrical isomeric derivatives established from spectroscopic data. The ability of the aminopropenes to antagonize histamine-induced contractions of the guinea-pig ileum is reported. These data allow various structure-activity relations to be discussed including stereochemistry (cis 2-pyridyl/H geometry is superior to cis substituted phenyl/H but not necessarily to cis phenyl/H), nature of the basic function (1-pyrrolidino is markedly superior to either dimethylamino or 1-piperidino) and the importance of the vinylic hydrogen atom (sharp falls in potency follow its replacement by methyl).
Potential irreversible inhibitors of acetylcholinesterase: N-trimethyl-N‘-iodoacetyl diaminoalkane iodides
Authors: BEDDOE F , NICHOLLS P J , SMITH H J
Published: April 2011

Potential irreversible inhibitors of acetylcholinesterase based on N-trimethyl-N'-iodacetyl diaminoalkane iodide Me3N+[CH2]n-NHCO·CH2I·I-, (I; n = 4) and (II; n = 2) have been prepared. (I) and (II) are both competitive inhibitors of the enzyme with Ki, 5·9 times 10−4m and 1·2 times 10−3m respectively. (I) is a partial agonist and (II) is a true agonist at the muscarinic receptor of guinea-pig ileum.
Sulphamethoxydiazine crystal forms
Authors: MOUSTAFA M A , EBIAN A R , KHALIL SAID A , MOTAWI M M
Published: April 2011

Methods of preparation of three polymorphs, two solvates and an amorphous modification of sulphamethoxydiazine are described. Infrared spectroscopy and X-ray diffraction data are given for the characterization of the various forms. The interconversion of these forms under various conditions of heating, suspension in water and grinding is studied. The dissolution behaviour of the different forms is also discussed. All forms on heating to 150° change to the same form and on suspension in water change to another water-stable form.
A rapid method for the determination of salicylate binding by the use of ultrafilters
Authors: SPECTOR REYNOLD , KORKIN DENISE T , LORENZO A V
Published: April 2011

An ultrafiltration method that combines speed, simplicity, accuracy and precision was employed to measure plasma binding of salicylate. Human plasma, containing 1·0 and 0·1mm sodium salicylate, was ultrafiltered through membranes using 45 p.s.i. and slow rotational stirring. Salicylate was bound at these concentrations 13·1 and 4·4% respectively. This method, using membranes that quantitatively separate small molecules from plasma proteins, yields results comparable to those obtained by equilibrium dialysis.
Inotropic effects of atropine on ureteral muscle
Authors: CUTHBERT A W , ŠEFERNA I
Published: April 2011

Atropine (1–10 μg ml) produced an inotropic effect in the smooth muscle of the guinea-pig isolated ureter. This appeared to be caused by an increase in the safety factor for conduction in this muscle. Whether the effect of atropine is exerted directly on the muscle fibres or via intramural nerves is discussed.
Detection and identification of trace steroids in prednisolone
Authors: COMPERNOLLE F , VANDERHAEGHE H , NONCLERCQ M
Published: April 2011

Prednisolone samples from different commercial sources produced during 1965–1970 were examined by thin-layer chromatography on silica gel in the system chloroform-methanol-water (180:15:1). When large quantities were applied on the plates several trace compounds were detected. These were eluted from the silica gel and identified by mass spectrometry. The presence of 20-dihydro- prednisolone, hydrocortisone, prednisone, 11-desoxyprednisolone, 21-desoxyprednisolone, and prednisolone 21-acetate was detected. The Δ5-isomer of prednisolone was also found, but this product probably is an artifact formed during the isolation procedure. The different impurities also could be detected in prednisolone after chromatography in the system dichloromethane-dioxan-water (2:1:1). Impurities found in the British Chemical Reference Standard Prednisolone were hydrocortisone (very weak), prednisone and an unidentified product present at the start.
Metabolism of amphetamines. Identification of N-oxygenated products by gas chromatography and mass spectrometry
Authors: Beckett A H , Coutts R T , Ogunbona F A
Published: April 2011

A sensitive method for the isolation and identification of N-oxygenated metabolites and metabonates of medicinal amines is described. A combination of gas chromatography and mass spectrometry is effective in separating and identifying secondary hydroxylamines, oximes and nitrones, all of which are N-oxygenated products of secondary amines. These products give mass spectra containing diagnostic fragment ions which are of great value in identification. Primary hydroxylamines are oxidized on column to oximes and can be separated and identified as such. This oxidation is avoided if the primary hydroxylamine is introduced by direct inlet into the mass spectrometer. Secondary hydroxylamines are more stable during gas chromatographic examination although some decomposition to nitrone and secondary amine does occur. In contrast, oximes and nitrones show no tendency to decompose when gas chromatographed.
The action of vasoactive drugs on longitudinal and circular muscle of dog mesenteric vein
Authors: Hall W J , O'Connor P C
Published: April 2011

The dog anterior mesenteric vein has outer longitudinal and inner circular muscle layers. The response of the vein to drugs was recorded without disrupting the muscle arrangements by combining constant-flow perfusion of a segment with isometric recording of longitudinal tension. Noradrenaline and acetylcholine were potent stimulants. Tachyphylaxis developed to histamine, 5-hydroxytryptamine and angiotensin. Cocaine and guanethidine potentiated the responses to noradrenaline and fluorescent microscopy confirmed the presence of adrenergic nerves in both muscle layers. Isoprenaline partially relaxed the stimulated vein and this action was blocked by propranolol. Evidence was obtained which suggests the existence in the vein of specific receptors for several of the agonists investigated.
The effect of submaximal doses of pentagastrin on gastric acid secretion, histamine and histidine decarboxylase in rats
Authors: Weidle E , Sewing K-FR
Published: April 2011

In Lai-rats gastric mucosal histamine and histidine decarboxylase were estimated after stimulation of gastric acid secretion by intravenous infusions of submaximal doses of pentagastrin for 1 or 2 h. Pentagastrin produced a dose-dependent acid response with a maximum of 26 μ equiv H+ per 10 min at a dose of 2.56 μg kg−1 min−1. There was a linear relation between the log dose of pentagastrin and the activation of gastric histidine decarboxylase. The highest dose of pentagastrin yielded a histidine decarboxylase activity of 200% of the unstimulated level when infused for 1 h and of 290% when infused for 2 h. No reduction of gastric mucosal histamine could be detected whatever the dose of pentagastrin or the duration of infusion. It was concluded (1) that stimulation of gastric histidine decarboxylase is a physiological function of gastrin-like peptides, (2) that a reduction of gastric mucosal histamine by gastrin or pentagastrin is a pharmacological rather than a physiological effect, and (3) that no negative feedback relation exists beween gastric mucosal histamine and the activation of histidine decarboxylase.
Oscillatory testing of o/w emulsions containing mixed emulsifiers of the surfactant-long chain alcohol type: self-bodying action
Authors: Barry B W , Eccleston G M
Published: April 2011

Liquid paraffin-in-water emulsions stabilized by cationic (cetrimide) or non-ionic (cetomacrogol) surfactants and cetostearyl alcohol were examined at 25° in oscillatory mode, using the Weissenberg Rheogoniometer with parallel plates coupled to a digital transfer function analyser. Ternary systems, formed by dispersing the mixed emulsifiers in water, were similarly investigated. Each preparation was tested in the linear viscoelastic region, and fundamental rheological parameters, the storage modulus (G') and the real viscosity (ẽ') were derived as functions of frequency over the range 7.91 times 10−4to 25 Hz. All ternary systems behaved similarly with respect to frequency. As this increased, G' rose and ẽ' fell. These trends were related to the viscoelastic nature of the systems. Both mixed emulsifiers exhibited self-bodying mechanisms, so that emulsion consistency increased as the mixed emulsifier concentration rose. This was shown by increases in G' and ẽ' at each frequency. The shapes of the plots and other rheological properties were related to viscoelastic gel networks formed in the emulsion continuous phases. The ternary system parameters implied that emulsion networks were similar to ternary gels, that is, they formed by the interaction of long chain alcohol and aqueous surfactant solution. The oscillatory data were compared and correlated with creep data derived for similar ionic and non-ionic dispersed systems, previously described.
An analysis of the inter-subject variation in the metabolism of pentazocine
Authors: Vaughan D P , Beckett A H
Published: April 2011

Significant inter-subject variation in the cumulative urinary excretion of pentazocine, following its oral administration, was observed. Individual variations in the rate of metabolic oxidation of pentazocine are responsible for the variations in the urinary excretion of pentazocine (24 h cumulative). Smoking did not affect the metabolism of the drug. Pharmacokinetic analysis of the urinary excretion rate of pentazocine, using an open three compartment model, indicated that the fractional metabolic clearance is correlated with the cumulative urinary excretion (24 h) of the drug under conditions of acidic urinary pH. A g.l.c. method for the determination of pentazocine in urine is described.
The actions of some anticholinesterase drugs on skeletal muscle in culture
Authors: Harvey A L , Dryden W F
Published: April 2011

The actions of the anticholinesterase drugs, physostigmine, neostigmine and diisopropylfluorophosphate (DFP) on chick embryonic skeletal muscle in culture were studied. None of the anticholinesterases potentiated depolarization responses to acetylcholine. In high concentrations neostigmine and physostigmine produced depolarization. The neostigmine-induced, but not the physostigmine-induced, depolarization was antagonized by tubocurarine. DFP caused an increase in the rate of repolarization during the presence of a cholinomimetic. It is concluded that the cholinesterase present in cultured muscle fibres does not have a physiological role in hydrolysing acetylcholine and that physostigmine and DFP have an action at the ionic channels that are linked to the cholinoreceptor.
Gas-liquid chromatographic estimation of lignocaine, ethylglycylxylidide, glycylxylidide and 4-hydroxyxylidine in plasma and urine
Authors: Adjepon-Yamoah K K , Prescott L F
Published: April 2011

Gas-liquid chromatographic methods have been developed for the estimation of lignocaine and its metabolites ethylglycylxylidide (EGX), glycylxylidide (GX) and 4-hydroxyxylidine in plasma and urine. Lignocaine, EGX and GX were extracted from alkaline solution, the metabolites were acetylated and the three compounds were chromatographed simultaneously using single column temperature programming with a nitrogen-sensitive flame ionization detector. The limits of detection were 10–30 ng ml−1. Conjugated 4-hydroxyxylidine in urine was hydrolysed with glusulase and chromatographed as the acetyl derivative.
Compression characteristics of powders: radial die wall pressure transmission and density changes
Authors: Carless J E , Leigh S
Published: April 2011

An instrumented single punch tablet machine was used to study the relations between axial pressure, radial die wall pressure and density changes in beds of powder undergoing compression. Aspirin, sodium chloride, paracetamol, paracetamol-polyvinylpyrrolidone and sucrose crystals were examined. The development and transmission of radial pressure during loading and unloading of the bed is discussed in relation to yield and elastic behaviour of the powder. The relation between mean stress and relative density of the compact is explained on the basis of plastic flow and/or crushing of the particles. Differences in stress vs density relations due to difference in particle size of sucrose were due to initial packing conditions in the die and not to differences in pressure transmission.
The fate of intravenous [3H]glycopyrrolate in man
Authors: Kaltiala Eero , Penttilä Aneri , Vapaatalo Heikki , Larmi Teuvo
Published: April 2011

Glycopyrrolate was labelled in one methyl group with tritium and its fate was studied in six patients with T-tube drainage by determining serum levels as well as the biliary and urinary excretion of radioactivity after intravenous injection. More than 90 % of the radioactivity had disappeared from serum in 5 min and after 30 min almost no radioactivity could be found. The highest radioactivity in bile was found in samples taken 30 or 60 min after the injection. However, measurable radioactivity was found in most cases after 48 h. The first urine samples (0–3 h) showed the greatest radioactivity, and in 48 h 85% of the total radioactivity was excreted into the urine. Paper chromatography showed that both in bile and in urine over 80% of the radioactivity corresponded to unchanged glycopyrrolate. That appreciable amounts of glycopyrrolate were excreted into the bile suggests that the spasmolysis achieved with glycopyrrolate could be based partly on a local action on the bile ducts.
A Polarographie method for the determination of the N-oxide, N-oxide-sulphoxide and sulphoxide metabolites of chlorpromazine
Authors: Beckett A H , Essien E E , Smyth W Franklin
Published: April 2011

Cathode ray polarography has been used to measure chlorpromazine-N-oxide, N-oxide sulphoxide and chlorpromazine sulphoxide in mixtures. The response was linear when the metabolites were present in the range 10−5 to 5 times 10−8m in aqueous solutions. Reductive polarography of the mixed oxides in solution gave an additive wave from which individual oxides were determined by subtraction. Ultraviolet and Potentiometrie titration methods were used to determine the pKa values of the oxide metabolites of chlorpromazine. The mechanism of the reduction process was investigated using d.c. polarography and preparative micro-electrolysis. Polarographic analysis was applied to the determination of the metabolites after their separation from urine, plasma and microsomal preparations.
A quantitative gas-liquid chromatographic method for phorbol and related diterpenes as their acetates
Authors: Kinghorn A D , Evans F J
Published: April 2011

A qualitative and quantitative gas-liquid chromatographic technique has been described for the acetates of the parent alcohols of several irritant and co-carcinogenic factors of the genera Croton and Euphorbia. Four columns have been found to be useful for the identification of the acetates of phorbol, 4-deoxy-4α-phorbol, 12-deoxy-phorbol, ingenol and crotophorbolone. A mixed SE-30, E.G.S. column was used for quantitative analysis using codeine as internal standard. Percentage standard errors of the estimated relative weight ratios of diterpenes to codeine varied from 0·9 to 1·27% for between 21 and 42 estimations. With plant latex samples the total recoveries of added ingenol were 98·3 ± 3%. The method has been used to evaluate the latex of E. lathyris, E. millii, E. desmondi, E. triangularis and E. tirucalli. The same samples were also assayed by an irritancy biological assay developed by Hecker.
The cannabinoid content of Cannabis sativa L grown in England
Authors: Fairbairn J W , Liebmann J A
Published: April 2011

Twelve varieties of Cannabis sativa were grown out-of-doors in southern England during 1971 to 1973. Results show that for certain varieties highly active herbal cannabis can be produced. A warm climate with abundant sunshine does not therefore seem to be essential for high THC content. This was supported by results of growing plants in a greenhouse in varying lighting conditions including a limited period in total darkness. Considerable within and between plant variation was found and the importance of defining the plant part used, the stage of growth and the size of the sample is emphasized for comparative work involving quantitative results. Comparison of the present results with those for the same cannabis varieties grown in different parts of the world shows that all exhibit the same qualitative picture, that is, either THC-rich or CBD-rich. Since this chemical composition seems independent of environmental conditions it is inappropriate to refer to the two types as phenotypes; it is more likely that they represent two chemical races within the species Cannabis sativa L.
Competitive inhibition of Asp1-β-amide-Val5-angiotensin II by Sar1-Ile5-Ile8-angiotensin II in cat isolated cardiac muscle and coronary vessels
Authors: Türker R K , Hall M M , Bumpus F M
Published: April 2011

Interaction of Asp1-β-amide-Val5-angiotensin II with the 8-substituted analogue of Asp1-Ile5-angiotensin II, Sar1-Ile5-Ile8-angiotensin II, has been examined on the isolated perfused heart and isolated papillary muscle of the cat. The constrictor effect of angiotensin in the coronary vessels as well as its positive inotropic effect in the heart muscle have been shown to be competitively inhibited by Sar1-Ile5-Ile8-angiotensin II. The antagonistic potency and the duration of the antagonistic effect of the analogue in both coronary vessels and myocardium have been evaluated separately. The analogue has a higher antagonistic potency in coronary vessels than in heart muscle. The duration of the antagonistic effect of Sar1-Ile5-Ile8-angiotensin II was found to be longer in the heart muscle than in coronary vesesels. The possible mechanism of the antagonistic effect of Sar1-Ile5-Ile8-angiotensin II against Asp1-β-amide-Va15-angiotensin II is discussed.
A note on the interaction between two phosphated surfactants
Authors: Groves M J , Mustafa R M A , Carless J E
Published: April 2011

Evidence of an interaction between the water-soluble phosphated nonylphenolethoxylate (PNE) and the oil-soluble phosphated fatty alcohol ethoxylate (PFE) could not be obtained when the two compounds were mixed in the anhydrous state. However, measurements of refractive index, interfacial tension, density and viscosity of aqueous solutions of the two surfactants showed anomalies which were at a maximum when they were present in an approximately equal ratio by weight.

Thin-layer chromatography confirmed the anomalous properties of mixtures of the two compounds and it is suggested that these result from the formation of a complex material involving PNE, PFE and water.
On the pharmacology of Org 6368 (2β, 16β - dipiperidino - 5α - androstan - 3α - ol acetate dimethobromide), a new steroidal neuromuscular blocking agent
Authors: Sugrue M F , Duff N , McIndewar I
Published: April 2011

Org 6368 is a homologue of pancuronium bromide. Its interactions with other agents in the cat sciatic nerve-gastrocnemius muscle preparation revealed that paralysis was of the non-depolarizing type. This was confirmed in experiments using avian muscle. Org 6368 is a potent muscle relaxant being 2·4 times as potent as (+)-tubocurarine in the cat. Paralysis in the cat is rapid in onset and of appreciably shorter duration than that of pancuronium and (+)-tubocurarine. Repeated injections of the same dose of Org 6368 show no cumulative effect. Muscle relaxant doses generally cause a slight increase in both blood pressure and heart rate. Although its histamine-releasing capacity is greater than that of pancuronium it is less than that of (+)-tubocurarine. Org 6368 shares with pancuronium a very weak effect on both the muscarinic receptor and ganglionic transmission. Differences in the muscle relaxant profiles of Org 6368 and pancuronium are discussed.
Effects of a human plasma fraction on the release of chemotactic factors and anaphylatoxin from complement
Authors: Walker J R , Badcock J K , Ford-Hutchinson A W , Smith M J H , Billimoria F J
Published: April 2011

A fraction prepared from normal human plasma inhibits the release of chemotactic factors and anaphylatoxin when complement is activated by the alternate but not by the classical pathway. The fraction gave no interference with the actions of the released substances on either leucocytes or guinea-pig isolated ileum. The possible relation of this effect to the mechanism of the anti-inflammatory actions of the plasma fraction is discussed.
Surface tension and cloud point changes of polyoxyethylenic non-ionic surfactants during autoxidation
Authors: Donbrow M , Hamburger R , Azaz E
Published: April 2011

Changes in the surface tension-concentration curves of the non-ionic surfactant cetomacrogol, a polyoxyethylenic (POE) hexadecyl ether containing about 24 ethylene oxide (EO) groups, have been examined during autoxidation of aqueous solutions. The curves exhibit decreases in cmc values and changes in the slopes below and above the cmc which lead to the loss of the sharp break characteristic of micelle-formation. There is also a progressive decrease in the cloud point during autoxidation. Surface tensions and cloud points of a series of known POE hexadecyl ethers containing from 10 to 60 EO units have been measured and related to the number of EO units present. From these data, it is apparent that autoxidation of cetomacrogol is accompanied by degradation of the POE chain rather than the hydrocarbon chain, the number of EO units lost up to the time at which the solution becomes turbid being about 14. The significance of such measurements is discussed in relation to the detection of decomposition and pending rapid decomposition in synthesized and commercial surfactants.
An anomalous effect of the intermediate products of riboflavine photolysis on the intestinal absorption of poorly absorbed water-soluble drugs in rats
Authors: Ghazy F S , Kimura T , Muranishi S , Sezaki H
Published: April 2011

The influence of the intermediate products of riboflavine photolysis on the absorption of poorly absorbed water-soluble drugs from the rat small intestine has been examined using an in situ recirculation technique. The absorption of phenol red, bromphenol blue (BPB) and their biliary excretion, and lactose isonicotinoyl-hydrazone (lactose-INH) and its plasma concentration were increased in experiments made in the presence of light in contrast to others made in the dark. The absorption of both phenol red and lactose-INH were concentration-dependent. On the other hand, a saturation phenomenon was demonstrated when the concentration of phenol red was kept constant while that of the water-soluble compound flavine mononucleotide (FMN) was changed. The results which were obtained from pretreatment experiments suggest an alteration in the permeability of the intestinal membrane. No enhancement effect could be demonstrated for lumichrome in the presence or absence of light.
The effect of waxes, hydrolysed gelatin and moisture on the compression characteristics of paracetamol and phenacetin
Authors: Obiorah B A , Shotton E
Published: April 2011

Stearic acid or hard paraffin added to crystals of paracetamol and phenacetin reduced capping of tablets prepared by direct compression but did not produce acceptable tablets because the inter-particular bonds were very weak. The pressure cycle that can be constructed from the measurement of the axial pressure and the corresponding die wall pressures offers information that is useful in the formulation of tablets. The behaviour of paracetamol or phenacetin and their mixtures with gelatin hydrolysate or water or both shows a similarity to a Mohr body and it appears that the maximum die wall pressure is affected by the particle size of the material compressed and also by the additives present. Good transmission of radial force implies that the material can be initially consolidated, but alone it does not indicate that the tablet formed is physically stable. When the tablet formed remains coherent after the axial pressure is removed the residual die wall pressure remains high. Measurement of the residual die wall pressure might therefore be a useful indicator for identifying satisfactory formulations of substances that cap readily. Hydrolysed gelatin or water or both together produced paracetamol and phenacetin mixtures with satisfactory compression characteristics.
Data point weighting in pharmacokinetic analysis: intravenous paracetamol in man
Authors: Clements J A , Prescott L F
Published: April 2011

Compartmental analysis of plasma paracetamol concentrations following intravenous injection of 12 mg kg−1 in aqueous solution to normal subjects was performed using analogue and digital computer methods. Using a ‘simplex’ non-linear optimization procedure, the pharmacokinetic parameters were found to be influenced considerably by the choice of the weighting factors (Wi) attributed to individual data points. The plasma half-life of paracetamol varied by up to seven-fold with the weighting factors selected. However, the predicted mean steady-state plasma concentrations were shown to be relatively little affected by the different weighting factors.
A comparison of the binding constant (Kd) of 125I-labelled 3-(4-iodophenoxy)-1-isopropylamino-propan-2-ol obtained on β-adrenoceptors in guinea-pig myocardial membranes, with its dissociation constants (Kb) obtained on guinea-pig isolated atria and trachea
Authors: O'Donnell Stella R , Woodcock Elizabeth A
Published: April 2011

The dissociation constant of binding (KD) of 125I-labelled 3-(4-iodophenoxy)-1-isopropyl-aminopropan-2-ol (IIP) to guinea-pig myocardial membrane preparations was 2·2 × 10−8m. In pharmacological experiments with the non-labelled material and 60 min contact time, IIP produced a parallel shift in the orciprenaline concentration-response line on guinea-pig isolated tracheal and atrial preparations. The dissociation constant (Kb) of IIP was 2·9 × 10−8m on atria (pA2 7·54) and 3·3 × 10−8m on trachea (pA2 7·48). These values indicate that IIP is not a selective β-adrenoceptor blocking drug. In addition, agreement was found between the affinity constant of this antagonist for β-adrenoceptors as determined by a direct binding study and an indirect pharmacological study.
Stimulation of human platelets by carrageenans
Authors: McMillan R M , MaCintyre D E , Gordon J L
Published: April 2011

The rank order of four carrageenans tested as inducers of human platelet aggregation was the same (iota > lambda > gelcarin > kappa) as their relative inflammatory potencies in vivo. All four carrageenans caused some precipitation of plasma proteins, and induced aggregation in platelet-rich plasma or washed platelet suspensions. The second phase of aggregation was citrate-dependent and associated with secretion of 5-hydroxytryptamine and lysosomal enzymes. Platelets could provide a useful model for investigating the actions of carrageenans on cell membranes.
Compactibility of granules prepared by a novel method of granulation and their dissolution
Authors: Ho Tak , Hersey John A
Published: April 2011

Increasing particle size during prolonged grinding by a ballmill has been used as a novel means of producing a pharmaceutical granulation. The compactibility properties of granules of sodium chloride and of paracetamol produced by this method have been elucidated and compared with those produced by conventional granulation techniques. Force-displacement diagrams and double compactions were used to measure the net energy input on tableting. When compared with conventional granulation methods, the agglomerative phase of comminution (APOC) method produced mechanically stronger tablets with a higher dissolution rate than those compacted from granules made by a conventional wet granulation method irrespective of the compaction energy used. Tablet tensile strength is related to the elasticity and yield strength of the substance used. It is suggested that binderless tablets may be prepared using this method, thus simplifying tablet formulation and enhancing stability. A possible mechanism for the increased dissolution rate is the increased internal surface area of the granules produced by the prolonged grinding method.
Thermodynamic parameters of molecular complexes in aqueous solution: enthalpy-entropy compensation in a series of complexes of caffeine with β-naphthoxyacetic acid and drug-related aromatic compounds
Authors: DONBROW M , SAX PHILIP
Published: April 2011

Stability constants and thermodynamic parameters have been evaluated for the complexation reaction in aqueous solution of caffeine with β-naphthoxy acetic acid. The values were higher than those previously reported for the complexation of other ligands with methyl xanthines. In nearly all aromatic ligands complexing with caffeine and theophylline for which data are available, both entropy and free energy of complexation were linearly related to the enthalpy, giving an isoequilibrium relationship. Salicylamide, sodium benzoate and cis-methyl cinnamate exhibited slight deviations on the ΔG-ΔH plot; the non-aromatic dehydroacetic acid showed the largest deviation. The isoequilibrium relationship was shown to be valid statistically (349–365 K, caffeine systems; 353–372 K, caffeine and theophylline systems) indicating underlying chemical causation. Thermodynamic equations are presented for analysis of the factors involved, which are attributed to a combination of substrate-ligand interactions and solvent effects. The substrate-ligand overlap area is considered as a common parameter through which the solvent and interaction forces might cooperate to give rise to linearity in the isoequilibrium relationship. The increasingly negative experimental values of the enthalpy and entropy with increase in ligand planar overlap area are discussed in relation to the underlying forces involved in the complexation.
The influence of gel formulation on the diffusion of salicylic acid in polyHEMA hydrogels
Authors: WOOD J M , ATTWOOD D , COLLETT J H
Published: April 2011

The influence of solute concentration, gel hydration, and crosslinking density on diffusion rates in polyHEMA hydrogels has been investigated using a radio-tracer technique. At hydrations above 31% water, diffusion is by pore flow, and increases in the crosslinking density of gels bring about a decrease in the diffusion coefficient, D. Below 31% hydration, diffusion is predominantly by solution diffusion and changes in crosslinking density have little effect on the diffusion coefficient. The diffusion coefficient is invariant with solute concentration within the range reported, although at a very high solute concentration, for the gels of lower hydration, the diffusion coefficient is higher than expected. A high value for D may be due to saturation of the binding sites of the diffusant on the polymer chains, leaving a greater proportion of diffusant available for transport.
A novel conjugate as a major metabolite of bromperidol in man
Authors: HAWKINS D R , BIGGS S R , BRODIE R R , CHASSEAUD L F , MIDGLEY I
Published: April 2011

The major urine metabolites of the neuroleptic drug, bromperidol, after oral doses to rats and dogs are p-fluorophenylacetic acid and its glycine conjugate resulting from oxidative N-dealkylation. While the same metabolites were also detected in human urine, also present was a major unknown component representing 50% of the total urine metabolites, which apparently was not formed by rats and dogs to any extent. Mass spectroscopic investigations of the metabolite showed that it could be thermally degraded to bromperidol and contained a substituent attached to the tertiary hydroxyl group. The mass spectrum of the metabolite after trifluoroacetylation was consistent with an O-glucofuranosiduronolactone conjugate of bromperidol.
Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system
Authors: KOLASA K , FUSI R , GARATTINI S , CONSOLO S , LADINSKY H
Published: April 2011

Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25–30% was produced at the dose of 20 mg kg−1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.
Determination of porosity variations in powder beds
Authors: WOODHEAD P J , HARDY J G , NEWTON J M
Published: April 2011

A gamma-ray attenuation technique for detecting local porosity variations in packings of pharmaceutical powders has been developed and assessed. It proved necessary to employ an empirical expression describing the attenuation coefficient of the model material, lactose, as a function of porosity. The precision of measurement of local porosity can be pre-selected due to the statistical basis of the method, and local porosity measurements with 95% confidence intervals of ±0.005 can readily be carried out. A method of producing grey-scale images of porosity distributions has been employed to enable the degree of inhomogeneity of a powder bed to be seen.