bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action of some bisquaternary derivatives of phthalic acids and related substances on neuromuscular transmission
Authors: DANILOV A. F. , KVITKO I. J. , LAVRENTIEVA V. V. , MICHELSON M. J. , PORAI‐KOSHITS B. A. , ROZHKOVA E. K. , SHELKOVNIKOV S. A. 
Published: July 2012

Summary
All the bisquaternary derivatives of terephthalic acid with three methyl groups on each nitrogen atom (PK‐107, PK‐95, PK‐97 and PK‐126) were depolarizing neuromuscular blocking agents. The most active was the compound PK‐97, in which the two quaternary groups are separated by sixteen atoms and are about 20 Å (2 nm) apart. Activity was reduced many fold either by decreasing the separation to twelve atoms or by increasing it to eighteen atoms. It was also reduced several hundred fold when one trimethylammonium group in PK‐97 was replaced by a hydrogen atom (as in PK‐119).
The presence and position of the ester groups in these compounds is important; depolarizing activity is in most cases greatest when the ester groups are the same distance from the quaternary nitrogen atoms as in acetylcholine, that is, in carbolonium, sebacoyldicholine and PK‐154. The monoquaternary analogues of carbolonium and sebacoyldicholine are appreciably active, having between about one‐tenth to one‐fifth of the activity of their bisquaternary analogues.
The relationships between the structure and activity of these compounds are discussed, particular consideration being given to the structure of the chain separating the quaternary groups and the arrangement of acetylcholine receptors on cells and of esterbinding groups within these receptors.
Renal excretion of metolazone, a new diuretic
Authors: BELAIR E. J. , COHEN A. I. , YELNOSKY J. 
Published: July 2012

Summary
Metolazone, a new diuretic, was found to be excreted by glomerular filtration and renal tubular secretion.
The secretory mechanism was antagonized by probenecid but this did not affect the diuretic action of metolazone.
Effects of McN‐A‐343 and DMPP on the uptake and release of 3H‐noradrenaline by guinea‐pig atria
Authors: ALLEN G. S. , RAND M. J. , STORY D. F. 
Published: July 2012

Summary
McN‐A‐343 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammoniuin chloride and DMPP (N,N‐dimethyl‐N'‐phenylpiperazinium iodide) inhibit the uptake of (±)‐3H‐noradrenaline by guinea‐pig atria, being approximately as potent as cocaine in this respect.
The inhibition of uptake produced by McN‐A‐343 or DMPP was not affected by atropine or hexamethonium in concentrations which antagonized actions on muscarinic and nicotinic receptors respectively.
McN‐A‐343 in the presence of atropine had a positive inotropic action on atria, but this was not accompanied by efflux of radioactivity from atria previously incubated with (—)‐3H‐noradrenaline.
In the presence of McN‐A‐343, responses of atria to noradrenaline were increased and those to tyramine were decreased.
DMPP had positive inotropic and chronotropic actions on atria, and these effects were accompanied by an increase in efflux of radioactivity from atria previously incubated with (—)‐3H‐noradrenaline.
A quantitative study of the anticholinergic action of several tricyclic antidepressants on the rat isolated fundal strip
Authors: ATKINSON J. , LADINSKY H. 
Published: July 2012

Summary
Investigations were carried out on the antagonism of the action of carbamylcholine chloride on the isolated fundus of the rat stomach by several tricyclic antidepressants.
The anticholinergic potency of the compounds was in the order: GP 45437>amitriptyline>protriptyline>desmethylimipramine>opipramol. All of the antagonists were less effective than atropine.
Statistical analysis was carried out to determine whether the theory of competitive antagonism would fit the data obtained.
The effects of cigarette smoking on the response to stress in a driving simulator
Authors: ASHTON HEATHER , SAVAGE R. D. , TELFORD ROSEMARY , THOMPSON J. W. , WATSON D. W. 
Published: July 2012

Summary
Some behavioural and physiological responses of cigarette smokers and non‐smokers exposed to varying degrees of stress in a driving simulator were compared.
When the smokers were smoking a cigarette, some of their reaction times to light signals differed significantly from those of non‐smokers, some being longer and some shorter. These differences disappeared when the smokers were not smoking.
Of the physiological measurements, only heart rate differed significantly between smokers and non‐smokers, being higher at all levels of stress in the smokers. There were no significant differences in blood pressure, calf blood flow and respiration rate between smokers and non‐smokers.
The results of the Cattell Sixteen Personality Factor Questionnaire showed that the smokers were significantly more extroverted and self‐reliant than the non‐smokers.
The results are discussed in relation to the pharmacology of cigarette smoking. It is concluded that the differences in reaction times and heart rates between smokers and non‐smokers were a consequence of cigarette smoking.
Actions of the sympathomimetic bronchodilator, rimiterol (R798), on the cardiovascular, respiratory and skeletal muscle systems of the anaesthetized cat
Authors: BOWMAN W. C. , RODGER L W. 
Published: July 2012

Summary
The actions of rimiterol [erythro(3,4‐dihydroxyphenyl, 2‐piperidyl methanol hydrobromide)], a new sympathomimetic bronchodilator, have been compared with those of salbutamol and laevoisoprenaline on the heart and lungs, and on contractions of the soleus muscle of cats under chloralose anaesthesia.
Rimiterol and salbutamol injected intravenously were about equipotent in all tests, and were about 8 times less potent than laevoisoprenaline both in opposing the bronchoconstrictor action of 5‐hydroxytryptamine, and in decreasing the tension and degree of fusion of incomplete tetanic contractions of the cat soleus muscle. They were about 19 times less potent than laevoisoprenaline in increasing heart rate.
The effect on the soleus muscle is considered to be analogous to the muscle tremor that often occurs in man, and the results therefore suggest that systemic administration of bronchodilator doses of rimiterol, like salbutamol, may produce muscle tremor as an unwanted side‐effect.
When equipotent doses to oppose 5‐hydroxytryptamine‐induced bronchospasm were compared, rimiterol and salbutamol produced less tachycardia than did laevoisoprenaline. In order to match the tachycardia produced by laevoisoprenaline, the doses of rimiterol or salbutamol had to be increased about two and a half times. This safety margin for salbutamol in the cat is considerably less than that reported by others for different species, which suggests that β1‐ and β2‐adrenoceptors may be less clearly differentiated in the cat than they are in other laboratory animals.
The effect of cold storage on the inhibitory action of isoprenaline, phenylephrine and nicotine on the mechanical and membranal activities of guinea‐pig taenia caecum
Authors: FUKUDA HIROYUKI , SHIBATA SHOJI 
Published: July 2012

Summary
The effects of prolonged cold storage on the mechanical and membranal responses to stimulation of α‐ and β‐adrenoceptors by phenylephrine and isoprenaline, respectively, were studied on the guinea‐pig taenia caecum.
Cold storage invariably caused a decrease in the resting membrane potential, and this effect was enhanced as the duration of treatment was prolonged.
After cold storage (18 days) the tissue potassium ion content (89·7 ± 1·7 mmol/kg wet wt.) was decreased to 30·5 ± 1·9 mmol/kg wet wt. whereas that for sodium (69·2 ± 1·4 mmol/kg wet wt.) increased to 134·0 ± 2·3 mmol/kg wet wt.
In the fresh preparations, phenylephrine (1 and 2 μm) caused a cessation of spontaneous action potentials, accompanied by hyperpolarization of the membrane and relaxation of the muscle. These effects were markedly diminished after 18 days of cold storage. Isoprenaline (1 and 2 μm) also blocked the action potentials and caused a concomitant muscle relaxation, but in most cases the hyperpolarization was not observed. After 14 days of cold storage these mechanical and membranal changes associated with isoprenaline treatment were not demonstrable in most preparations.
Nicotine (5 μm and 50 μm) produced a biphasic effect, cessation of the action potential, hyperpolarization and subsequent relaxation followed by a long lasting depolarization, an accelerated discharge of action potentials and an increase in muscle tension. After a few days of cold storage the hyperpolarization effect disappeared but the intensity of the long‐lasting depolarization as well as the contractile effects were increased. After cold storage for more than 7 days, nicotine did not affect mechanical or electrical activity.
Dibutyryl 3′5′ cyclic AMP (1 μm to 500 μm) failed to affect the mechanical and electrical activities of taenia caecum.
Phenylephrine and isoprenaline had no effect on the high potassium‐depolarized taenia.
These observations suggest that the electro‐mechanical effect of an α‐adrenoceptor stimulant on the guinea‐pig taenia caecum is more resistant to cold treatment than that of a β‐adrenoceptor stimulant. This inhibitory system of stimulation of both α‐ and β‐receptors of guinea‐pig taenia caecum may react by different mechanisms. The results also demonstrate that cold storage itself changes the membrane permeability to ions and the tissue ion content (Na+ and K+) of smooth muscle of guinea‐pig taenia caecum.
Effects of enzyme inhibitors of catecholamine metabolism and of haloperidol on the pancreatic secretion induced by l‐DOPA and by dopamine in dogs
Authors: FURUTA Y. , HASHIMOTO K. , IWATSUKI K. , TAKEUCHI O. 
Published: July 2012

Summary
Effects of inhibitors of DOPA decarboxylase, dopamine β‐hydroxylase and monoamine oxidase, and haloperidol on the secretion of pancreatic juice induced by l‐DOPA and dopamine were studied in preparations of the isolated blood‐perfused canine pancreas.
The increased secretion induced by the infusion of l‐DOPA (100 μg/min) was completely antagonized by Ro 4–4602 (300 μg), a DOPA decarboxylase inhibitor.
The secretogogue effect of dopamine (1–10 μg) intra‐arterially was not affected by Ro 4–4602, but was enhanced by the infusion of fusaric acid (100 μg/min), a dopamine β‐hydroxylase inhibitor.
The increase in the secretion induced by dopamine (1–10 μg) was enhanced by treatment with nialamide (100 mg/kg), a monoamine oxidase inhibitor, given intravenously.
Haloperidol (1 mg) intra‐arterially attenuated the dopamine‐induced pancreatic secretion.
It is concluded that l‐DOPA is converted to dopamine in the acinar cells which causes an increase in the secretion of pancreatic juice, thus the intracellular level of dopamine may be controlled by enzymatic equilibrium.
The prejunctional actions of some non‐depolarizing blocking drugs
Authors: BLABER L. C. 
Published: July 2012

Summary
Trains of end‐plate potentials (e.p.p.s) have been recorded from the isolated tenuissimus of the cat. The muscle was paralyzed either by transversely cutting the muscle fibres or by non‐depolarizing blocking drugs.
The following parameters of transmitter synthesis, storage and release have been calculated: the quantal content of the first e.p.p. in the train, the size of the available store, fractional release, quantum size, and the rate of refilling of the available store.
Tubocurarine and benzoquinonium depressed the rate of refilling of the available store causing its depletion at high rates of stimulation. This was offset by an increase in fractional release, which in the case of tubocurarine was sufficient for the quantal content of the first e.p.p. to be unchanged.
Dimethyltubocurarine and pancuronium had a similar effect to tubocurarine on the rate of refilling of the store and depletion of the store at high rates of stimulation but did not increase fractional release. There was, therefore, a decrease in the quantal content of the first e.p.p.
Lignocaine depressed the rate of refilling of the store and depleted the store at high rates of stimulation. Fractional release was also depressed.
It is suggested that the non‐depolarizing drugs have a weak local anaesthetic action retarding the influx of sodium into the nerve terminal which slows the rate of refilling of the store. This effect is due to the quaternary ammonium head. The presence of a phenolic group increases fractional release due either to an increased influx of calcium into the nerve terminal or to a potentiation of the actions of calcium.
Influence of allopurinol on drug metabolism in man
Authors: RAWLINS M. D. , SMITH S. E. 
Published: July 2012

Summary
Elimination rates of phenylbutazone and warfarin after single oral doses in human volunteers, and steady‐state plasma concentrations of these drugs in patients have been measured before, during and after administration of allopurinol.
Allopurinol, in usual clinical doses, had no significant influence on the elimination rate of either drug in the group of volunteers as a whole although in a few individuals an apparent inhibitory effect was observed.
No significant changes in the steady‐state plasma concentrations of either phenylbutazone or warfarin were observed in patients during the administration of allopurinol.
It is concluded that although allopurinol may have an apparent inhibitory effect on drug elimination in a few individuals, its administration to most patients on anticoagulant therapy is unlikely to alter dose requirements.
Influence of chloride ions on changes in membrane potential during prolonged application of carbachol to frog skeletal muscle
Authors: JENKINSON D. H. , TERRAR D. A. 
Published: July 2012

Summary
Micro‐electrodes were used to follow changes in the membrane potential at the end‐plate region of single fibres in narrow strips of frog skeletal muscle exposed to carbachol applied in continuously flowing Ringer solution containing tetrodotoxin (200 nm) and neostigmine (3 μm).
The depolarizations elicited by carbachol (5–20 μm) usually developed in two phases, the first of which was generally complete within 30 s whereas several min were required for the second.
Repolarization after carbachol also occurred in two phases, the second of which outlasted the time needed to clear the bath, and varied with the magnitude and duration of the depolarization which carbachol had caused.
These findings could best be explained in terms of the consequences of net entry of chloride ions into the fibre during the depolarization caused by carbachol. This hypothesis is supported by three lines of evidence:

Replacement of the chloride content of the Ringer solution by the less permeant anion isethionate abolished the slow phases of the carbachol response.
Reduction of chloride permeability (by lowering pH) caused rapid repolarization during the recovery period after carbachol.
When the membrane potential was clamped at the resting level throughout the action of carbachol, so avoiding chloride redistribution, the clamping current records did not show the slow phases attributed to chloride movement.

Chloride redistribution contributes to the gradual spread of depolarization during prolonged applications of depolarizing agents to skeletal muscle. It also complicates the interpretation of the dose‐response relationship, and may make it more difficult to assess the extent to which the receptors become desensitized during the action of agonists applied in the bath.
On the pharmacology of the glycine receptors on the cuneo‐thalamic relay cells in the cat
Authors: KELLY J. S. , RENAUD L. P. 
Published: July 2012

Summary
In cats either decerebrated or anaesthetized with sodium pentobarbitone, strychnine released by iontophoresis from electrodes containing a 5 mm solution in 165 mm of NaCl, abolished the action of glycine and β‐alanine on cuneo‐thalamic relay cells without disturbing their response to equally effective applications of γ‐aminobutyric acid (GABA) and β‐guanidino‐propionic acid.
The loss of glycine sensitivity appeared to increase as long as the strychnine release continued until even the largest currents tolerated by the electrode were unable to eject effective amounts of glycine. Parallel shifts of the glycine log‐current response curves, equivalent to an equipotent dose‐ratio of about 20 only occurred when the duration of the strychnine applications by current in excess of 28 nA was restricted to a few minutes.
Without modifying either the frequency of the spike discharge or the amplitude or shape of the action potential, currents larger than 28 nA occasionally caused a loss of GABA sensitivity.
Strychnine administered either intravenously (0·2 mg/kg) or applied topically to the surface of the cuneate (0·5 mm) blocked the response to glycine without any obvious effect on the response to GABA.
It was concluded that the discovery of a strychnine‐sensitive component of the inhibitory potentials recorded from the cuneate nucleus will reveal the physiological role of the glycine receptors on cuneo‐thalamic relay cells.
Acute systemic anaphylaxis in the horse
Authors: EYRE P. , LEWIS A. J. 
Published: July 2012

Summary
Histamine in small doses caused systemic depressor responses in horses, whereas greater doses caused biphasic effects. All doses of 5‐hydroxytryptamine (5‐HT) were pressor and all doses of bradykinin depressor. All three active substances raised pulmonary artery pressure and lowered central venous pressure. 5‐HT reduced ventilation volume. Histamine caused brief apnoea followed by hyperpnoea only.
Acute anaphylaxis in the horse was accompanied by a severe systemic arterial depressor response, a pressor response in the pulmonary artery and vena cava, and alternating phases of apnoea and dyspnoea.
During anaphylaxis, profound haemoconcentration, leucopoenia, thrombo‐cytopoenia and hyperkalaemia were in evidence. Early during anaphylactic shock (2 to 4 min) there were profound increases in plasma histamine (five to six‐fold) and plasma kinin activity (four to five‐fold). Plasma 5‐HT concentrations were reduced initially but recovered. Later in anaphylaxis (10 to 20 min) whole blood histamine concentration fell significantly. This coincided with the most profound period of leucopoenia.
No significant differences were observed in histamine concentration in any of five tissues between six ponies subjected to anaphylaxis and six controls. Mast cell numbers were not reduced but mast cells were more metachromatic (pink) and there was spilling of mast cell granules.
Gross pathological changes were noted mainly in the lungs which were extensively oedematous and congested. Inflamed, congested and oedematous areas in the large colon and caecum were seen, and the kidneys, spleen and liver were engorged. Alveolar emphysema, peribroncheolar oedema (containing mononuclear cells and neutrophils) were recorded. Alveoli contained erythrocytes.
The action of bombesin on the kidney of the anaesthetized dog
Authors: ERSPAMER V. , MELCHIORRI P. , SOPRANZI N. 
Published: July 2012

Summary
In the anaesthetized dog bombesin had a potent antidiuretic effect, and sometimes arrested urine flow completely. Threshold doses, by i.v. infusion, were of the order of 0·5–1 (ng/kg)/minute. Antidiuresis was the result of a reduction in glomerular filtration rate provoked by a fall in intraglomerular hydrostatic pressure. This, in its turn, was due to afferent vasoconstriction.
The spasmogenic effect of bombesin on the smooth muscle of the afferent arterioles was directly demonstrated by the radioactive microspheres technique and indirectly by the 85Kr washout method and by [3H]‐p‐aminohippurate clearance. The vascular compartment most sensitive to bombesin was that of the outer cortical zone, especially in its external half.
Filtration fraction decreased under the influence of bombesin, indicating that the effect of the polypeptide on postglomerular arterioles was, if present, only of minor importance.
At high infusion rates (above 6 (ng/kg)/min), bombesin produced a decrease in [3H]‐p‐aminohippurate extraction. The effect of the polypeptide on fractional distal delivery of sodium varied with the dose: at moderate infusion rates it decreased, at high infusion rates it increased. The total glucose appearing in urine following a glucose load was sharply reduced by bombesin. However, the glomerular filtration rate/maximum tubular glucose transport ratio did not show any appreciable change.
Afferent vasoconstriction produced by bombesin was accompanied by an intense activation of the renin‐angiotensin system, as shown by a conspicuous increase in renin secretion, followed by increases in renin activity and angiotensin II concentration in arterial blood. When bombesin was infused into one renal artery only the infused kidney showed afferent vasoconstriction and increased renin secretion. The time‐course of renin secretion produced by bombesin depended upon the rate of infusion of the polypeptide. At low rates an increased renin secretion was observed throughout the infusion period, at high rates two peaks of renin secretion could be seen, one at the beginning of the infusion, the other soon after the infusion had finished.
The mechanism of action of bombesin is discussed and the interest of the polypeptide as a possible hormonal regulator of the circulation and function of the kidney is pointed out.
A study of compounds which initiate and block nerve impulses in the perfused rabbit liver
Authors: ANDREWS W. H. H. , ORBACH J. 
Published: July 2012

Summary
A technique for the perfusion of the rabbit liver with Krebs solution is described: the hepatic nerves were monitored for centripetal action potentials. Spontaneous afferent activity, and a good response to stimulating agents persisted for 7 h or longer.
Action potentials were elicited by injections or infusions of acetylcholine, 5‐hydroxytryptamine, bradykinin, phenyldiguanide, adrenaline and various other compounds. From comparison with experiments carried out in vivo by other authors, it would appear that most of the nerves stimulated were afferent.
Inhibition of action potentials, either those occurring spontaneously or those elicited by injections, was produced by aspirin, paracetamol, mepyramine, chlorpheniramine, procaine and lignocaine but not by morphine or atropine. Pentolinium produced some inhibition, as did hexamethonium in concentrations of about 7·5 μg/ml.
Three methods for using the preparation for the assessment of local anaesthetic action are described.
Lobeline, potassium cyanide and 2,4‐dinitrophenol stimulated nerve bundles which were not stimulated by anoxia or hypoxia.
The time courses of the changes in contractile force and in transmembrane potentials induced by cardiac glycosides in guinea‐pig papillary muscle
Authors: LÜLLMANN H. , RAVENS URSULA 
Published: July 2012

Summary
The effects of ouabain, digoxin, digoxigenin monodigitoxoside, digoxigenin bisdigitoxoside and digitoxigenin bisdigitoxoside on the force of contraction and on the transmembrane action potential were compared in isolated papillary muscles of guinea‐pigs.
All cardiac glycosides studied had a dose‐dependent positive inotropic effect and simultaneously shortened the duration of the action potential at all levels of repolarization from the start of drug action.
In every instance, the reduction of the action potential duration developed more slowly than the increment in contractile force. However, the ratios between the two rates were independent of the concentrations used and seemed to be characteristic for the individual cardiac glycosides.
All cardiac glycosides had a biphasic effect on the time‐to‐peak tension. An initial increase was followed by a dose‐dependent decrease.
The results are discussed with respect to the possible sites of action. Taking into account the different rates as well as the different ratios, it is proposed that more than one site of action is involved in producing the different effects of cardiac glycosides on heart muscle.