bluuebunny/crossref_metadata_2025_split huggingface dataset:
A third class of anti‐arrhythmic action. Effects on atrial and ventricular intracellular potentials, and other pharmacological actions on cardiac muscle, of MJ 1999 and AH 3474
Authors: SINGH B. N. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

Summary
Both MJ 1999 and AH 3474 protected guinea‐pigs anaesthetized with urethane against ouabain‐induced ventricular fibrillation.
MJ 1999 had 1/90, and AH 3474 1/30, of the activity of procaine in reducing the height of the action potential of frog sciatic nerve.
MJ 1999 and AH 3474 reduced the rate of rise of intracellularly recorded action potentials at concentrations in excess of 160 × 10−6m (50 mg/l.). It was concluded that direct depression of depolarization could have contributed little to the protection against ouabain‐induced fibrillation.
MJ 1999, but not AH 3474, greatly prolonged the duration of the action potential in acute experiments on isolated atrial and ventricular muscle, and prolonged the Q‐Tc interval of the electrocardiogram in anaesthetized guinea‐pigs. It is suggested that this effect contributes to anti‐arrhythmic activity.
At concentrations up to 80 × 10−6m AH 3474 had positive chronotropic and inotropic effects on isolated rabbit atrial muscle, but at higher concentrations these were superseded by negative effects. MJ 1999 was depressant at all concentrations studied, the threshold concentrations being 19 × 10−6m for chronotropic, and 162 × 10−6m for inotropic effects.
Effects of drugs acting alone and in combination on the motor activity of intact mice
Authors: FRANK G. B. , JHAMANDAS K. 
Published: July 2012

Summary
When administered to intact white mice, the central depressants—diphenhydramine, promethazine, chlorpromazine, gammahydroxybutyrate, gammabutyrolactone, hyoscine, and pethidine—produced sedation in small doses, but excitement and convulsions in higher doses. When given to mice pretreated with subanaesthetic doses of phenobarbitone these drugs abolished the righting reflex both in convulsant doses (hyoscine excepted) and in non‐convulsant doses. These effects are similar to the effects previously observed with local anaesthetics.
Meprobamate, diazepam and chlorpromazine produced a loss of righting reflex both when given alone and following phenobarbitone. When given alone in higher doses, chlorpromazine induced convulsions.
The central stimulants bemegride and picrotoxin antagonized the loss of righting reflex produced by phenobarbitone, but nikethamide, caffeine and strychnine did not alter the depressant effects of phenobarbitone.
On the basis of these and previous studies with intact white mice a tentative classification of drugs having generalized depressant and stimulant effects on the central nervous system was proposed and discussed.
The role of monoamine oxidase in the response of the isolated central artery of the rabbit ear to tyramine
Authors: LANDE I. S. de la , HILL B. D. , JELLETT L. B. , McNEIL J. M. 
Published: July 2012

Summary
Monoamine oxidase activity was demonstrated histochemically throughout the media of the rabbit ear artery but not in the adventitia at its border with the media where the sympathetic nerve terminals are concentrated. Neither intensity nor distribution of enzyme activity was perceptibly altered up to 60 days after sympathetic denervation.
Iproniazid and nialamide increased the sensitivity of the artery to intraluminal tyramine much more than that to extraluminal tyramine, so that the difference between the potencies for the two routes of administration became less marked.
The results indicate that inactivation by monoamine oxidase in the media is a factor contributing to the relatively low potency of intraluminal tyramine on the artery.
Effects of hemicholinium and bretylium on the release of autonomic transmitters in the isolated sino‐atrial node
Authors: APPEL W. C. , VINCENZI F. F. 
Published: July 2012

Summary
In the isolated, spontaneously beating, sino‐atrial node of the rabbit selective electrical excitation of intranodal autonomic nerve fibres results in a biphasic chronotropic response. This chronotropic response (negative followed by positive chronotropism) is due to the release of the autonomic transmitters (acetylcholine and noradrenaline, respectively) from intranodal nerve fibres.
In the presence of 2 × 10−4 g/ml hemicholinium, the negative chronotropic (cholinergic) response is abolished while the positive chronotropic (adrenergic) response is unaltered.
In the presence of 5 × 10−6 g/ml bretylium, the positive chronotropic response is abolished while the negative chronotropic response is little affected.
After blockade of the negative chronotropic response by hemicholinium, bretylium abolishes the remaining positive chronotropic response. The effect of bretylium is not altered in the presence of hemicholinium.
Considering currently accepted mechanisms of action for hemicholinium and bretylium, the results of these experiments do not lend support to the cholinergic link hypothesis of adrenergic neuro‐effector transmission.
Effects of adenosine 3‘,5’‐monophosphate on renal function in the rabbit
Authors: BARRACLOUGH M. A. , JONES N. F. 
Published: July 2012

Summary
Intravenous injections of adenosine 3′,5′‐monophosphate (cyclic‐AMP) were given to five conscious, diuretic rabbits, and the effects on urinary flow and composition were compared with those of intravenous injections of vasopressin given to the same animals.
Cyclic‐AMP produced antidiuresis with increases in urinary osmolality and in the urinary concentrations of creatinine, urea and usually of sodium.
The fractional reabsorption of urea from renal tubular fluid increased during cyclic‐AMP induced antidiuresis.
The effects of cyclic‐AMP thus closely resembled those of vasopressin and are consistent with the view that cyclic‐AMP mediates the action of this hormone.
Actions of some sympathomimetic bronchodilator and beta‐adrenoceptor blocking drugs on contractions of the cat soleus muscle
Authors: BOWMAN W. C. , NOTT M. W. 
Published: July 2012

(–)‐Isoprenaline, salbutamol, orciprenaline and quinterenol injected intravenously decreased the tension and degree of fusion of incomplete tetanic contractions of the soleus muscle of the anaesthetized cat.
Under the most sensitive conditions, the smallest effective dose of (–)‐isoprenaline was of the order of 0.01 μg/kg intravenously. Salbutamol was usually 6–10 times, orciprenaline 20–30 times and quinterenol about 35 times less potent than isoprenaline. The effects of salbutamol were about 1.6 times, of orciprenaline about 1.8 times and of quinterenol more than 20 times as long lasting as those of (–)‐isoprenaline.
The effects of the sympathomimetic amines were blocked by propranolol, H56/28, H35/25 and butoxamine but not by ICI 50172. The combined results with agonists and antagonists indicate that the receptors involved can be classified as of the β2 type.
The effect of the amines on the cat soleus muscle appears to be analogous to that causing enhancement of physiological tremor in man, which suggests that skeletal muscle tremor may be an occasional unwanted side effect of the use of these bronchodilators.
Inhibition of the development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis
Authors: COX B. M. , OSMAN O. H. 
Published: July 2012

A study has been made of the effects of a number of drugs which have as a common property the ability to inhibit RNA or protein synthesis, on the development of tolerance to the analgesic effects of morphine, given by intravenous infusion, in rats.
Measurements were also made of the effects of the drugs on the incorporation of 14C‐lysine into rat brain protein, and 14C‐orotic acid into rat brain RNA.
Actinomycin D, 6‐mercaptopurine and 5‐fluorouracil reduced the acquisition of tolerance to morphine at doses which also produced significant inhibition of incorporation of orotic acid into brain RNA. Tolerance development was only affected by 6‐mercaptopurine and 5‐fluorouracil after intracerebral administration.
6‐Mercaptopurine and 5‐fluorouracil did not significantly affect the incorporation of lysine into protein, although a small but significant reduction in lysine incorporation was produced by infusion of actinomycin D at 20 μg/kg per hr.
Development of tolerance to the analgesic effects of morphine was also reduced by cycloheximide and puromycin. These drugs markedly reduced the incorporation of lysine into brain protein. Puromycin and low doses of cycloheximide (50 μg/kg per hr) did not significantly affect RNA synthesis as measured by orotic acid incorporation, but RNA synthesis was clearly reduced by administration of cycloheximide at 200 μg/kg per hr.
These results support the hypothesis that the synthesis of new RNA and protein in the brain is an essential feature of the development of tolerance to morphine in rats.
Effects of drugs on tremor and increase in brain acetylcholine produced by oxotremorine in the rat
Authors: COX B. , POTKONJAK D. 
Published: July 2012

In rats the effect of drugs on oxotremorine tremor and oxotremorine‐induced increase in brain acetylcholine has been investigated.
Reserpine, (±)‐α‐methylmetatyrosine and diethyldithio‐carbamic acid, drugs which have in common the ability to decrease tissue noradrenaline concentration, inhibited oxotremorine tremor without preventing the oxotremorine‐induced increase in brain acetylcholine.
(±)‐p‐chlorophenylalanine, a depletor of tissue 5‐hydroxytryptamine, did not inhibit oxotremorine tremor.
Phenoxybenzamine and propranolol inhibited oxotremorine tremor, and propranolol was without effect on oxotremorine‐induced increase in brain acetylcholine.
The toxicity of oxotremorine was increased by reserpine and phenoxybenzamine.
The significance of these findings is discussed with regard to the mode of action of oxotremorine.
Mechanisms of histamine release by compound 48/80
Authors: ROTHSCHILD A. M. 
Published: July 2012

Rat and guinea‐pig lung tissues were incubated for 20 min at 37° C in Krebs‐Ringer phosphate buffer at pH 7.4, or in Tyrode‐Tris buffer at pH 8.2, and the release of histamine produced by adding different concentrations of compound 48/80 to the incubation medium was determined.
At pH 7.4, increasing concentrations of 48/80 increased the release of histamine from the rat lung, with a tendency towards a maximum. No release of histamine from guinea‐pig lung was observed at this pH. At pH 8.2, histamine release occurred both from rat and guinea‐pig lung, and was proportional to the logarithm of the concentration of compound 48/80.
Histamine release from rat lung by 20 μg/ml. of 48/80 decreased when the pH was raised from 7.4 to 8.2; but the release caused by 1 mg/ml. of 48/80 increased both in rat and guinea‐pig lung as the pH was raised.
2–4‐Dinitrophenol (DNP) inhibited the release of histamine from rat lung by a concentration of 20 μg/ml. of 48/80; the inhibition was prevented by glucose. DNP did not affect histamine release from rat or guinea‐pig lung by a concentration of 1 mg/ml. of 48/80 and enhanced the release when the pH was raised from 7.4 to 8.2.
1 mg/ml. of 48/80 did not inhibit the enhanced oxygen consumption produced by DNP in the isolated rat diaphragm.
Iodoacetic acid (IAA) or a Ca/Mg‐free medium inhibited the release of histamine by 20 μg/ml. of 48/80 from rat lung but not the release produced by 1 mg/ml. in either rat or guinea‐pig lung.
The degranulation of rat mesentery mast cells caused by 20 μg/ml. of compound 48/80 was inhibited by DNP. The degranulation evoked by 1 mg/ml. of 48/80 was also sensitive to this inhibitor; in this instance, however, the metachromatic staining reaction of the mesentery mast cells was greatly diminished.
It is concluded that two processes of histamine release by compound 48/80 occur in rat lung. One, dependent on cell metabolism, involves mast cell granule secretion. The other, independent of cell metabolism, seems to consist of a simple exchange reaction between histamine and compound 48/80, and this is the only one occurring in guinea‐pig lung.
Effects of amphetamine derivatives on brain dopamine and noradrenaline
Authors: BREESE G. R. , KOPIN I. J. , WEISE VIRGINIA K. 
Published: July 2012

Summary
. Intracisternally administered metaraminol, α‐methyl‐octopamine, α‐methyl‐m‐tyramine, and α‐methyl tyramine were found to lower brain noradrenaline without having an effect on brain dopamine.
. Amphetamine, mephentermine, and norephedrine had no effect on brain catecholamines after intracisternal injection.
. There was no reduction in brain dopamine content after intracisternal injection of α‐methyl‐m‐tyramine, yet the resulting brain concentration of α‐methyl‐m‐tyramine was several times higher than after intraperitoneal injection of α‐methyl‐m‐tyrosine, which decreased brain dopamine.
. The decreased synthesis of labelled catecholamines from 14C‐tyrosine after α‐methyl‐m‐tyrosine suggested that this compound inhibits tyrosine hydroxylase in addition to its action of displacing brain amines.
The concentration of catecholamines in the brain of the domestic fowl (Gallus domesticus)
Authors: CALLINGHAM B. A. , SHARMAN D. F. 
Published: July 2012

Summary
. The concentrations of adrenaline and noradrenaline in the brains of chickens (Gallus domesticus) have been determined using two different methods of fluorimetric analysis.
. The concentrations of adrenaline, noradrenaline and also dopamine were found to increase with age, as did the relative amount of adrenaline present in the chicken brain.
. It was observed that the differential assay of adrenaline by the trihydroxyindole method often underestimated the amount of adrenaline present.
Actions of some cholinergic antagonists on fast‐twitch and slow‐twitch skeletal muscle of the cat
Authors: BRIMBLECOMBE R. W. , EVERETT SALLY D. 
Published: July 2012

Summary
. The anticholinergic drug N‐ethyl‐2‐pyrrolidylmethylcyclopentylphenyl glycollate (PMCG) has been studied for its effects on the contraction of fast‐twitch (flexor hallucis longus, FHL) and slow‐twitch (soleus) muscles in the cat.
. In both muscles lower doses (0·25 to 10 mg intra‐arterially) potentiated and higher doses (10 mg and above) depressed twitches produced by indirect stimulation. Similar effects were obtained in directly stimulated muscles.
. The effects of the drug on muscles stimulated repetitively were dependent on both dose and frequency of stimulation. Doses which potentiated twitches also potentiated low frequency tetani (5–30 Hz for soleus; 10–50 Hz for FHL). There was a depression and non‐maintenance of higher frequency tetani (80 Hz and above for soleus; 150 Hz and above for FHL).
. Both atropine and caramiphen had similar dose dependent potentiating and depressant actions. Hyoscine acted similarly in some cats; in others it had only a depressant action.
. It is suggested that the potentiating actions of PMCG, caramiphen, atropine and hyoscine are due to a direct musculotropic action. The depressant actions resulting from higher doses are due, in part, to a curare‐like action and in part to a direct action on the muscle fibres.
Studies on the antibacterial and antifungal properties of 1, 4‐naphthoquinones
Authors: AMBROGI V. , ARTINI D. , de CARNERI I. , CASTELLINO S. , DRADI E. , LOGEMANN W. , MEINARDI G. , DI SOMMA M. , TOSOLINI G. , VECCHI E. 
Published: July 2012

Summary
. New halogenated 1,4‐naphthoquinones were synthesized and together with other known 1,4‐naphthoquinones, were screened for antibacterial activity by a turbidimetric method, and for antifungal activity by the diffusion method on agar plates.
. The half‐wave potentials and the influence on the oxidative phosphorylation of some of these compounds were determined.
. 2‐chloro‐3,2′‐chloro‐ethyl‐1,4‐naphthoquinone (half‐wave potential = −187 mV) was the most active compound, completely inhibiting cell respiration.
. While the natural active naphthoquinones, vitamin K and ubiquinones, possess, as substituent, the electron repelling methyl group, the microbiologically active 1,4‐naphthoquinones are substituted, in the quinone moiety, with electron attracting groups such as OH or Cl.
. The half‐wave potentials can give only an initial indication of the activity of the compounds studied; a good correlation, on the contrary, can be found between the ultraviolet spectra of such compounds and their activity which seems to depend on the ability of active compounds to exist in an extensively conjugated structure and to form hydrogen bonds.
Pharmacological properties of centrally administered ouabain and their modification by other drugs
Authors: DOGGETT N. S. , SPENCER P. S. J. 
Published: July 2012

Summary
Ouabain given by intracerebroventricular injection to mice in small doses (0·1–0·4 μg) produced a dose related depression of central nervous activity, characterized by a reduction in spontaneous locomotor activity, hypothermia, catalepsy and ptosis, lowered body posture and lack of response to external stimuli. Doses above 0·4 μg were excitatory, convulsant and lethal.
The depressant effects could be antagonized by (+)‐amphetamine, desmethylimipramine, dibutyryl cyclic 3′5′‐adenosine monophosphate and caffeine.
The MAO inhibitor nialamide produced only a small antagonism of ouabain, resulting in a greater rate of recovery from the depressant effects of ouabain.
The depressant effects were associated with a marked elevation of whole‐brain dopamine levels with little change in noradrenaline or 5‐hydroxytryptamine.
The dopamine‐β‐hydroxylase inhibitor sodium diethyldithiocarbamate, administered by intracerebroventricular injection, produced effects qualitatively similar to those seen after ouabain.
An interference with central transmitter function is postulated as a possible mode of action of intracerebroventricularly injected ouabain.
Effect of paraoxon on erythrocyte metabolism as measured by oxygen uptake in vitro
Authors: SANTOLUCITO J. A. , WHITCOMB E. 
Published: July 2012

Summary
Oxygen consumption in vitro and persistence in the general circulation of rabbit erythrocytes treated with the cholinesterase inhibitor paraoxon were determined.
Paraoxon in vitro reduced oxygen consumption below a measureable level within 2 hours. By contrast, the metabolic inhibitor N‐ethylmaleimide (NEM) produced complete inhibition within 15 minutes.
Erythrocytes from rabbits orally dosed with parathion also exhibited marked depression of oxygen consumption.
Glutathione (GSH) restored oxygen uptake to pretreatment levels within 15 min in erythrocytes previously inhibited with NEM or paraoxon.
Erythrocytes treated with NEM were rapidly removed from the general circulation while paraoxon treated cells were removed at a rate comparable to untreated cells.
Intracellular enzymes and protein synthesis in rabbit skin after thermal injury
Authors: LEWIS G. P. , PETERS JUDY , WHITE A. M. 
Published: July 2012

Summary
The concentrations of several intracellular enzymes in rabbit skin have been measured 5 min, 2, 6 and 24 h after thermal injury.
At 5 min and 2 h after a burn (60° C for 1 min) there was a significant fall in the enzyme activities whereas at 6 h their activities were higher than control.
It appears that the increase in enzyme concentrations in the lymph during the first few hours after thermal injury is associated with a fall in the enzyme concentrations in the tissues and therefore might be the result of leakage of enzyme from storage sites in the injured cells.
The second increase in enzyme concentrations in the lymph which has been observed 6–18 h after thermal injury occurs at a time when there is also an increase in the enzyme concentrations in the tissue.
It seems unlikely that these increased activities are due to new synthesis since there was no apparent correlation between tissue enzyme concentrations and protein synthetic activity, and the changes still occurred after administration of cycloheximide.
There was a change in the LDH isoenzyme pattern after injury towards a predominance of LDH‐1. This change did not occur immediately after the burn, but was present at 2 and 6 h, and returned to normal 24 h later.
Disturbed patterns of behaviour in morphine tolerant and abstinent rats
Authors: KUMAR R. , MITCHELL E. , STOLERMAN I. P. 
Published: July 2012

Summary
Eating, drinking and spontaneous motor activity were studied in rats receiving large daily doses of morphine. These forms of behaviour were largely suppressed when the rats were made abstinent and were restored when morphine was given again.
Compensation for depressions of behaviour during abstinence did not seem sufficient to account for all the stimulant effects of morphine in tolerant rats. Morphine also had slight stimulant actions in non‐tolerant rats.
In tolerant rats, the repeated pairing of the effects of morphine with the re‐emergence of behaviour such as eating and drinking may intensify the rewarding value of the drug.
Effects on cardiac muscle of the β‐adrenoceptor blocking drugs INPEA and LB46 in relation to their local anaesthetic action on nerve
Authors: SINGH B. N. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

Summary
As a local anaesthetic on frog nerve, LB46 had 0·4 times the activity of procaine and 2 times that of INPEA.
In reducing the maximum rate of depolarization (MRD) of intracellularly recorded cardiac action potentials, LB46 was 20 times more potent than INPEA.
As an antagonist of the chronotropic effect on atrial muscle and of the inotropic effects on ventricular muscle of isoprenaline the pA2 values for LB46 were 9·05 ± 0·15 and 9·30 ± 0·06 respectively, and for INPEA 6·00 ± 0·16 and 6·10 ± 0·12.
LB46 was 8 times more active than racemic propranolol in blocking the effects of isoprenaline on isolated cardiac muscle, and since its direct action on the cardiac membrane was only 0·1 times that of propranolol, there was a net gain of 80 times in the specificity of LB46 for class 2 (antisympathetic) over class 1 (depression of MRD) antidysrhythmic actions.
INPEA was 2·5 times less active as a β‐adrenoceptor blocking drug on cardiac muscle than (+)‐propranolol, and 1,300 times less active than LB46.
INPEA, but not LB46, prolonged the duration of both atrial and ventricular intracellular action potentials.