bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antagonism by fenamates and like‐acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea‐pig
Authors: COLLIER H. O. J. , JAMES G. W. L. , PIPER PRISCILLA J. 
Published: July 2012

Nine non‐steroidal anti‐inflammatory drugs were tested for antagonism of bradykinin‐induced bronchoconstriction in guinea‐pig lungs in vivo. Only one, benzydamine, was inactive.
The descending order of potency of the active anti‐inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>glafenine>ibufenac.
Of eight other drugs tested, chlorpromazine, phenoxybenzamine and four others were inactive, whereas phenelzine and mebanazine possessed activity.
In tests at two dose‐levels of meclofenamate, the dose‐ratio of bradykinin increased proportionately with the dose of meclofenamate.
The anti‐bradykinin effect of meclofenamate was still observed after destruction of the brain and spinal cord, after bilateral adrenalectomy or after blockade of β‐receptors for adrenaline.
Meclofenamate did not release catecholamines from the adrenal medulla or prevent such a release by bradykinin given intra‐arterially.
The fenamates and like‐acting drugs reduced the intensity of anaphylactic bronchoconstriction in guinea‐pigs treated with mepyramine or propranolol. The descending order of potency was meclofenamate>flufenamate>mefenamate.
Dose/response curves for the antagonism of anaphylactic bronchoconstriction by the fenamates, in the presence of propranolol, turned downwards at high doses.
These findings suggest that the fenamates may find a useful place in the treatment of bronchial asthma or other conditions involving allergic ventilatory impairment.
The action of acetylcholine and other drugs on the efflux of potassium and rubidium from smooth muscle of the guinea‐pig intestine
Authors: BURGEN A. S. V. , SPERO L. 
Published: July 2012

A method is described for measuring continuously the efflux of potassium or rubidium from smooth muscle of the guinea‐pig.
Muscarinic drugs cause at maximum a 100‐fold increase in the efflux rate, due to a direct increase in permeability and only to a minor extent secondary to depolarization. With acetylcholine the dose response curve for producing efflux is displaced to 1,000 times higher concentrations than that for contraction.
The shift varies with different agonists. The efflux and contractile responses to agonists are antagonized to an equivalent extent by atropine and several other reversible antagonists but benzhexol has a relatively greater effect on efflux. An estimate of spare receptors was obtained with benzilylcholine mustard and was similar for both responses. Dibenamine and local anaesthetics led to a parallel shift of the contraction dose response curve but a depression without shift in the efflux response.
The most satisfactory explanation of these results is that there are two types of the muscarinic receptor in the smooth muscle of the guinea‐pig intestine.
Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise
Authors: BRICK I. , HUTCHISON K. J. , McDEVITT D. G. , RODDIE I. C. , SHANKS R. G. 
Published: July 2012

The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responsesAfter the pre‐treatment of subjects with atropine or hexamethonium, I.C.T. 50172 produced a significant reduction in an isoprenaline tachycardia. This reduction was not competitive and did not exceed 50%.The intravenous injection of 4 mg I.C.I. 50172 reduced an exercise tachycardia; its effect was less than that of 4 mg propranolol. This difference became greater as the doses of the two drugs were increased. The dextro isomer of propranolol had no effect on the exercise tachycardia; I.C.I. 45763 reduced it to the same extent as propranolol.The intravenous injection of I.C.I. 50172 reduced the increase in heart rate produced by tilting a normal subject from the supine to 80° head‐up position. After the administration of atropine, I.C.I. 50172 almost abolished the response. In the presence of atropine, I.C.I. 50172 was as active as propranolol in reducing the increase in heart rate on tilting.The reason for the differences in the effects of I.C.I. 50172 on the increases in heart rate brought about by the three procedures is not clear.The increase in forearm blood flow produced by the infusion of isoprenaline into the brachial artery was not reduced by the intra‐arterial administration of I.C.I. 50172.
The assay of anti‐pyretic drugs in mice, using intracerebral injection of pyretogenins
Authors: CASHIN C. H. , HEADING CHRISTINE E. 
Published: July 2012

A simple, cheap, and reliable method is described for the screening of new compounds for anti‐pyretic activity. It involves the intracerebral injection of a suitable pyretogenin in conscious mice.
The pyretic response is related to the logarithm of the dose in a substantially linear manner when “E” Pyrogen is used.
A selection of established anti‐pyretic drugs were effective in oral doses approaching those used clinically, which shows that the method is unusually sensitive.
The response to intracerebral pyretogenin is not unduly influenced by drugs known to cause hypothermia.
It is suggested that “E” Pyrogen injected intracerebrally has a direct effect on the central nervous system, rather than an indirect action through release of endogenous pyrogen.
Taloximine, a new respiratory stimulant with bronchodilator properties
Authors: DALY M. J. , LIGHTOWLER J. E. , PICKERING R. W. 
Published: July 2012

A novel phthalazine analogue taloximine (1‐hydroxyimino‐4(2‐dimethylaminoethoxy)‐1, 2‐dihydrophthalazine monohydrochloride monohydrate) stimulated respiration in conscious rabbits at doses of 7 mg/kg and above.
Taloximine antagonized the depressant action of morphine on respiration in rabbits at doses of 10 mg/kg. At high doses it resuscitated rabbits after they had been given lethal doses of sodium pentobarbitone.
In in vitro preparations of the trachea or bronchus taloximine was about equiactive with aminophylline. In the Konzett‐Rössler preparation the intravenous ED50 for taloximine was about 18% of that of aminophylline, whereas after oral administration the two drugs were equiactive.
Taloximine, unlike aminophylline, did not protect guinea‐pigs against anaphylactic microshock to egg albumen.
Taloximine shortened the duration of the loss of righting reflex in mice due to hexobarbitone more effectively than bemegride, nikethamide or vanillic acid diethylamide.
In the dose required to stimulate respiration taloximine had only slight cardiovascular effects. Up to four times this dose produced no evidence of general excitation of the central nervous system.
Relationship between the uptake, binding and pharmacological action of procaine in the isolated heart
Authors: BOULLIN D. J. , SULLIVAN T. J. 
Published: July 2012

The uptake, efflux and pharmacological actions of procaine hydrochloride were studied on isolated hearts of female guinea‐pigs. The hearts were perfused with Krebs solution containing 14C‐procaine (0.1–500 μg/ml.) by the Langendorff technique at 37° C, using a constant flow pump. Hearts and cardiac effluent were assayed for procaine by liquid scintillation spectrometry.
Accumulation of procaine did not appear to involve active transport mechanisms for the following reasons. The rate of procaine uptake was most rapid at the highest perfusion concentration (500 μg/ml.), when it was three times faster than at the lowest concentration (0.1 μg/ml.); it was not affected by lowering the temperature to 3° C. The ratio of the concentration of procaine in the heart to the concentration in the perfusing fluid decreased with increasing concentration in the perfusion fluid.
When the efflux of 14C‐procaine from hearts previously perfused with procaine‐containing Krebs solution for 10 min was compared with the efflux of 14C‐inulin, the patterns of efflux of both compounds were similar, and showed at least two exponential components. At the highest concentration of procaine (500 μg/ml.) the efflux of procaine was more rapid than that of inulin.
A relationship was found between the pharmacological action of procaine, the rate of uptake and the level of procaine in the heart. When the procaine‐containing perfusion fluid was changed to a procaine‐free solution, the heart rate increased rapidly, and there was a rapid decline in the levels of procaine in the hearts.
It is concluded that guinea‐pig hearts accumulate procaine by a passive diffusion process, and that the pattern and rate of efflux indicate that the drug is loosely bound. If it is permissible to extrapolate from these findings to the antiarrhythmic effect in man, the short duration of its action may be due to loose binding rather than to rapid metabolic inactivation.
Metabolism and excretion of 3‐hydroxyphenyltrimethylammonium and neostigmine
Authors: HUSAIN M. A. , ROBERTS J. B. , THOMAS B. H. , WILSON A. 
Published: July 2012

Carbon‐14 labelled 3‐hydroxyphenyltrimethylammonium (3‐OH PTMA), an active metabolite of neostigmine, has been given to rats by intramuscular injection and its excretion, distribution and metabolism have been studied.
A method is described for the separation and estimation of free and conjugated 3‐OH PTMA in urine and liver.
In the first hour, about 20% of a dose is excreted in the urine as free 3‐OH PTMA and thereafter the rate of excretion of glucuronide conjugate exceeds that of free 3‐OH PTMA. In 24 hr 76.8% of the dose is excreted in urine mainly as the conjugate.
The peak concentration of radioactivity in blood occurs within 30 min and in liver within 1 hr after administration. More than 90% of the radioactivity in liver occurs as the glucuronide conjugate. Relatively high concentrations of radioactivity were found in liver and heart.
In the hen 3‐OH PTMA is rapidly excreted by renal tubular secretion.
Experiments with carbon‐14 labelled neostigmine show that up to 1 hr mainly unchanged neostigmine is excreted in urine; thereafter increasing amounts of free 3‐OH PTMA and its glucuronide conjugate are excreted.
It is concluded that the duration of action of neostigmine is determined by its rapid renal excretion and by its metabolism to the glucuronide conjugate of 3‐OH PTMA.
Interactions of ouabain and noradrenaline in isolated rabbit's atria
Authors: TODA N. 
Published: July 2012

The present study was made using sympathetic nerve‐atria preparations, conventional atrial preparations and left atria isolated from rabbits in order that interactions of ouabain and noradrenaline on the transmembrane potential of S‐A nodal pacemaker fibres, the pacemaker rate and the contractile force of the left atrium could be investigated.
In pacemaker action potentials, the maximal diastolic potential was decreased, the early repolarization was accelerated and the late repolarization was slowed by toxic concentrations of ouabain. Oscillating potentials of the diastolic pacemaker membrane were produced.
Stimulation of the postganglionic sympathetic nerve caused an increase in the slope of diastolic depolarization, resulting in an acceleration of the pacemaker rate. In the presence of ouabain, the pacemaker action potential configuration was significantly altered by nerve stimulation in preparations which showed ouabain‐induced bradycardia, but the potential configuration was not changed by nerve stimulation in preparations which showed ouabain‐induced tachycardia. Cardiac noradrenaline altered the ion permeability of the cardiac pacemaker membrane during diastole, but it had no effect during systole. Sympathetic nerve stimulation transiently corrected the overshoot and the repolarization of atrial action potentials altered by toxic concentrations of ouabain.
The positive chronotropic effect of sympathetic nerve stimulation was not affected by either therapeutic or toxic concentrations of ouabain. Ouabain shifted the concentration‐chronotropic response curve for exogenous noradrenaline to the left, but did not shift the curve for tyramine.
Relationship between the developed tension and the rate of contraction was altered differently by ouabain and by noradrenaline. The positive inotropic effect of noradrenaline was not significantly altered by therapeutic concentrations of ouabain but it was inhibited by toxic concentrations.
The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions
Authors: EVANS M. H. 
Published: July 2012

It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride.
Both saxitoxin and tetrodotoxin inhibit lithium‐generated action potentials. The concentration of toxin needed to inhibit the lithium‐generated action potentials is similar to that needed to inhibit sodium‐generated action potentials.
If magnesium chloride is added to the saline to give a concentration of 10–15 mm there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions.
Glycol metabolites of noradrenaline in brain tissue
Authors: SHARMAN D. F. 
Published: July 2012

A gas chromatographic method using electron capture detection is described for the estimation of those catecholamines and their metabolites which possess one or two free alcoholic hydroxyl groups. It is based on acetylation of phenolic hydroxyl and primary and secondary amino groups in aqueous solution, extraction into a water immiscible solvent and esterification of alcoholic hydroxyl groups with heptafluorobutyric anhydride.
The method has been successfully applied to the detection and estimation of free 4‐hydroxy‐3‐methoxyphenylethylene glycol (MOPEG) and free 3,4‐dihydroxyphenylethylene glycol (DOPEG) in hypothalamic brain tissue.
Although it was possible to measure noradrenaline and normetanephrine by the same method in pure solution, crude tissue extracts could not be used, despite their suitability for estimating the glycol metabolites.
Actions of adrenaline on the potassium balance of the isolated heart
Authors: STAFFORD ANNE 
Published: July 2012

The action of adrenaline on the K+ balance of the isolated heart was found to depend on the ionic composition and the temperature of the perfusion fluids used.
When the perfusion fluid contained 145 mm Na+, 1·7 mm Ca++ and 3–9 mm K+, adrenaline caused the hearts to gain K+; when the K+ concentration was reduced to 1·2 mm, adrenaline caused a loss of K+. Both were actions on β receptors.
When the Ca++ or the Na+ concentration in the perfusion fluid was reduced, together with a reduction in K+, adrenaline no longer produced K+ loss from the hearts, but produced a gain of K+.
When the temperature of the perfusion fluid was reduced to 25° C, adrenaline still produced a gain of K+ by hearts perfused with fluid containing 3·2 mm K+, but did not produce a loss of K+ from hearts perfused with fluid containing 1·2 mm K+.
Liberation of a bradykinin‐like substance in the circulating blood of dogs by trypsin, chymotrypsin and nagarse
Authors: FERREIRA S. H. , SILVA M. ROCHA E 
Published: July 2012

Using the blood‐bathed organ technique with cat jejunum as the test organ, it was shown that kinin was regularly released by infusions of trypsin, chymotrypsin and nagarse into the blood supervising the tissue or into the jugular vein of dogs.
Intravenous injections of the three enzymes, in doses which did not change plasma bradykininogen (BKG) level, induced generation of kinin in the circulating blood.
Nagarse in kinin‐liberating concentrations did not liberate angiotensin in the circulating blood.
The responses of the cat jejunum strip, and the systemic hypotension induced by the three enzymes, were enhanced by treatment of the dog with a bradykinin potentiator.
Injection of the enzymes in the blood perfused hind leg of the dog caused a fall in the vascular resistance. In this preparation, bradykinin potentiating factor (BPF) potentiated trypsin, but not the effects of chymotrypsin and nagarse injections.
It is suggested that the blood pressure lowering effect of low doses of trypsin is due mainly to kinin release. Chymotrypsin and nagarse, in addition to having a direct action on the vascular smooth muscles, also have indirect hypotensive effects due to the liberation of kinin.
The action of certain haloalkylamines on some biological activities of bradykinin
Authors: AL‐KATIB H. A. , BABA W. I. 
Published: July 2012

Bradykinin and histamine reduced the blood pressure in normotensive anaesthetized rabbits. They produced a pressor or biphasic response when the initial arterial pressure was lowered by acute haemorrhagic shock or mecamylamine blockade. When blood pressure was lowered by pretreatment with reserpine, bradykinin remained depressor and histamine produced a biphasic response.
Phenoxybenzamine abolished the pressor responses to bradykinin and histamine, but potentiated and prolonged the depressor response to bradykinin.
Phenoxybenzamine‐OH and SY28‐OH modified neither the pressor nor depressor responses to histamine, nor the pressor response to bradykinin. However, they greatly potentiated and prolonged the hypotensive effect of bradykinin.
In the isolated rabbit ear preparation, the initial vascular tone influenced the responses to bradykinin and histamine. In preparations having low vascular tone they were vasoconstrictors, but when the tone was raised by angiotensin or noradrenaline, they were vasodilatators.
Phenoxybenzamine blocked the vasconstrictor effect of bradykinin in a rabbit ear preparation having low vascular tone and phenoxybenzamine or its related ethanolamine potentiated the vasodilator response to bradykinin in preparations in which the tone was high.
The significance of these findings is discussed.
3H‐Nicotine in cat superior cervical and nodose ganglia after close‐arterial injection in vivo
Authors: BROWN D. A. , HOFFMANN P. C. , ROTH L. J. 
Published: July 2012

Concentrations of 3H‐nicotine in the superior cervical and nodose ganglia of anaesthetized cats were measured after close‐arterial injection.
Shortly after injection there was a higher concentration of 3H‐nicotine in the superior cervical ganglion than in the nodose ganglion. Mean concentration ratios, superior cervical ganglion/nodose ganglion (S/N ratios) were: 2 min after injection, 1.60 ± 0.19; 4 min, 1.21 ± 0.19; 8 min, 0.92 ± 0.05. These ratios were independent of the dose of nicotine over the range 4 to 200 μg in 0.2 ml.
There was no comparable difference in the concentrations of injected 14C‐inulin or 3H2O in the two ganglia, or in total water content.
Procedures which reduced the pharmacological action of nicotine (pre‐treatment with hexamethonium, admixture of 14C‐inulin) tended to reduce the S/N ratio for nicotine.
Autoradiographs showed that nicotine entered the neurones of both superior cervical and nodose ganglia.
It was concluded that the higher concentration of nicotine in the superior cervical ganglion was probably related to its selective pharmacological action at this site, and may have been due to a greater intracellular retention of nicotine.
An uptake of radioactivity from (±)‐3H‐isoprenaline and its inhibition by drugs which potentiate the responses to (—)‐isoprenaline in the guinea‐pig isolated trachea
Authors: FOSTER R. W. 
Published: July 2012

The uptake of radioactivity derived from (±)‐3H‐isoprenaline by the guinea‐pig isolated trachea has been measured, and the assumption is made that all the radioactivity is due to isoprenaline.
40% of the total (±)‐3H‐isoprenaline taken up was loosely bound to the tissue while 25% was firmly bound.
The firmly bound component of the uptake was more susceptible to inhibition by drugs than the loosely bound component.
Desipramine and cocaine did not reduce the accumulation of firmly bound isoprenaline.
Cooling to 23° C, guanethidine and phentolamine caused a moderate reduction in the accumulation of firmly bound isoprenaline.
Phenoxybenzamine and (±)‐metanephrine caused a highly significant reduction in the accumulation of firmly bound isoprenaline.
These findings are discussed in relation to previous studies of the uptake of isoprenaline and of other processes which may be related.
The inhibition of uptake by the agents examined correlated with their potentiation of the action of (—)‐isoprenaline found previously.
It is suggested that a tissue uptake can significantly modify the pharmacological response to isoprenaline in vitro.
Intra‐hepatic vascular response to sodium nitrite
Authors: GEUMEI AIDA , ISSA I. , MAHFOUZ M. 
Published: July 2012

In the perfused liver of the dog, sodium nitrite produced vasoconstriction in the hepatic arterial bed and, particularly, in the portal venous vascular bed.
These effects on the hepatic vasculature may account in part for the reduction of venous return and diminution in cardiac output recorded by other workers, and may therefore be a factor in the clinical efficacy of the nitrites in angina pectoris.
Possible protective action of antialdosterone compounds in myocardial necrosis in rats
Authors: MOUDGIL LALTA RANI 
Published: July 2012

Experimental myocardial necrosis was produced in rats by injection of large doses of isoprenaline.
The effectiveness of four aldosterone antagonists in preventing this myocardial necrosis was studied.
The relative effectiveness of these compounds in preventing isoprenaline‐induced necrosis was found to be Sc 5233>Sc 9420 (spironolactone)>Sc 11927 and Sc 8109.
The reported relative effectiveness of these compounds as aldosterone antagonists is Sc 11927>Sc 9420, Sc 8109>Sc 5233.
The significance of these findings is discussed.
Histochemical fluorescence studies on noradrenaline accumulation by Uptake2in the isolated rat heart
Authors: CLARKE D. E. , JONES C. J. , LINLEY P. A. 
Published: July 2012

. The distribution of noradrenaline accumulated by Uptake2(Iversen, 1965) in the isolated perfused rat heart has been observed using histochemical fluorescence microscopy.. On the basis of the technique used, noradrenaline seems to be predominantly associated with the cardiac muscle cells, but sympathetic nerves and other cardiac structures also serve as retention sites.. Phenoxybenzamine, normetanephrine and perfusion with noradrenaline at 20° C all decreased noradrenaline accumulation.. Lowered temperature significantly increased the perfusion pressure and significantly decreased the [14C]‐sorbitol space in perfused hearts.. The implications of these results are discussed.
Actions of phenylephrine on β‐adrenoceptors in guinea‐pig trachea
Authors: CHAHL LORIS A. , O'DONNELL STELLA R. 
Published: July 2012

. Phenylephrine produced relaxation of the isolated guinea‐pig tracheal chain preparation, its potency being 1/5 that of noradrenaline on normal tissues.
. The potentiation of phenylephrine by cocaine (10−5M) was only slight. Thus on cocaine‐treated tissues phenylephrine was 1/45 as potent as noradrenaline.
. The dose‐response lines to phenylephrine were shifted in a parallel manner by propranolol 10−8M and 10−7M, suggesting that the relaxations were mediated through β‐adrenoceptors.
. Phenylephrine had a lower intrinsic activity than the catecholamines and produced multiphasic dose‐response lines at the higher doses used in the presence of propranolol (10−6M). These observations have been explained by the evidence obtained that phenylephrine is a partial agonist with β‐adrenoceptor blocking activity.
. From experiments using α‐adrenoceptor blocking drugs, it has been concluded that stimulation of α‐adrenoceptors has little influence on the β‐adrenoceptor relaxation to phenylephrine on the guinea‐pig tracheal chain preparation.