bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of the cardiovascular actions of AQ 110 with those of isoprenaline and salbutamol
Authors: FOGELMAN F. , GRUNDY H. F.
Published: July 2012

. AQ 110 is a β‐adrenoceptor agonist which, like isoprenaline and salbutamol, acts directly on the receptors.

. Compared with isoprenaline, AQ 110 has relatively stronger actions on bronchial and vascular smooth muscle (β2‐adrenoceptors) than stimulant effects on heart muscle (β1‐adrenoceptors). The β2‐selectivity of AQ 110 is, however, much less than that of salbutamol, mainly due to the weak cardiac actions of the latter.

. At doses which were equipotent in decreasing the bronchoconstrictor effect produced by a standard dose of 5‐hydroxytryptamine, AQ 110 had marginally less hypotensive action than salbutamol and considerably less than isoprenaline.

. Although AQ 110, unlike salbutamol, possesses a catechol group it was found not to be a substrate for catechol‐O‐methyl transferase and this is considered to account for its significantly prolonged action, compared with isoprenaline, in vivo.
Physiological and drug‐induced changes in the glycogen content of mouse brain
Authors: HUTCHINS D. A. , ROGERS K. J.
Published: July 2012

. The effect of the method of killing on the concentration of glycogen in mouse brain was determined. The cerebral glycogen content of mice killed by immersion in liquid nitrogen did not differ significantly from that of animals decapitated and the heads immediately frozen. A delay before freezing led to the rapid loss of brain glycogen, with a 17% fall at 10 s and an 82% loss after 5 min.

. Hyperglycaemia, induced by the administration of d‐glucose, resulted in an 8.3% loss of brain glycogen after 120 min. Insulin hypoglycaemia produced a 10.7% fall in glycogen at 60 min followed by an 11.2% increase at 120 min.

. Exposure to either high (32° C) or low (10° C) ambient temperatures caused a depletion of brain glycogen.

. A circadian rhythm of brain glycogen concentration was found, with a nadir which was coincident with the peak of locomotor activity and body temperature.

. Drugs from several pharmacological classes were studied for their in vivo effect on the concentration of glycogen in mouse brain.

. Brain glycogen was increased by all the depressant drugs tested, and by some drugs which had little effect on behaviour (diphenhydramine, phenytoin and propranolol), or which caused excitation (caffeine and nialamide).

. Glycogen was depleted only by amphetamine‐like compounds or by bemegride‐induced convulsions.

. The results are discussed with particular reference to the possible relation between catecholamines and glycogen metabolism in the brain.
Pharmacology of some acetylcholine homologues
Authors: BARRASS B. C. , BRIMBLECOMBE R. W. , RICH P. , TAYLOR JOAN V.
Published: July 2012

. The acetates of several long chain (3 to 12 methylene groups) analogues of choline have been prepared and their pharmacological properties studied.

. None of the compounds had a high level of activity at the post‐ganglionic parasympathetic acetylcholine receptors. The lower members of the series showed weak agonist activity and the homologues with 8 to 10 methylene groups had very weak anticholinergic activity.

. All the compounds had a depolarizing action at the acetylcholine receptors of the neuromuscular junction and of sympathetic ganglia. At the neuromuscular junction there were two peaks of stimulant activity, one with the hexamethylene and one with the dodecamethylene homologue, whereas at the ganglion there was only one peak, with the hexamethylene homologue.

. The ganglion‐stimulant activity of the higher members of the series was blocked by pretreatment with the anticholinesterase drug dyflos, whereas the activity of lower members was either unaffected by such treatment or slightly potentiated.

. The results are discussed in terms of possible spatial arrangements of acetylcholine receptor units in the neuromuscular junction and the ganglion.
Lack of antagonism between thioglycerol and an oxytocin analogue not containing a disulphide bond
Authors: SCHILD H. O.
Published: July 2012

. The antagonistic effect of thioglycerol against oxytocin and an analogue of oxytocin not containing a disulphide bridge (desamino‐1‐carba‐oxytocin) has been compared in the rat isolated depolarized uterus.

. Thioglycerol clearly differentiated between the two compounds, 40 mm producing a dose ratio of 12 with oxytocin but only 1.5 with the carba compound.

. It was confirmed that thioglycerol produces no appreciable destruction of oxytocin in vitro.

. The mode of action of thiols in antagonizing specifically S–S polypeptides is discussed. It is concluded that they probably do not produce their effect either by inactivating receptors or by inactivating S–S polypeptides in solution. A possible mechanism is that thiols potentiate the destruction of S–S polypeptides at the receptor site.
Nonspecific supersensitivity of the guinea‐pig vas deferens produced by decentralization and reserpine treatment
Authors: WESTFALL D. P. , Burn J. H.
Published: July 2012

. The sensitivity of the guinea‐pig vas deferens to noradrenaline, histamine, methylfurmethide and potassium was examined in vitro following decentralization and reserpine treatment.

. One day after decentralization or administration of reserpine (1.0 mg/kg daily) the sensitivity of the vas deferens was not increased. After 5 days' treatment the muscle was supersensitive to all four stimulants.

. The magnitude of the sensitivity increase to an individual drug was the same following both chronic reserpine treatment and decentralization. However, the degree of supersensitivity differed for the four stimulants. The order of potentiation was noradrenaline>histamine>methylfurmethide>potassium.

. The magnitude of the supersensitivity was inversely correlated with the slope of the dose‐response curves to the four agonists. The dose‐response curve to potassium had the steepest slope, followed in order by methylfurmethide, histamine and noradrenaline.

. A hypothesis is presented to account for the inverse relationship between the slope of the dose‐response curve and the degree of supersensitivity which follows reserpine treatment or decentralization.
Studies on the interrelationship between the syntheses of noradrenaline and metaraminol
Authors: JOHNSON G. E. , PUGSLEY T. A.
Published: July 2012

. Experiments were conducted to determine the influence of the rate of noradrenaline synthesis on the conversion of alpha‐methyl‐m‐tyrosine to metaraminol.

. Male Wistar rats, 175–200 g, were placed into four groups and treated with (1) alpha‐methyl‐p‐tyrosine methyl ester, 250 mg/kg (2)dl‐alpha‐methyl‐m‐tyrosine, 400 mg/kg (3) alpha‐methyl‐p‐tyrosine methyl ester, 250 mg/kg plusdl‐alpha‐methyl‐m‐tyrosine, 400 mg/kg or (4) an equivalent volume of injection vehicle. All solutions were injected intraperitoneally.

. Immediately after treatment half of the rats were transferred to 4° C with the remaining animals being kept at 27° C.

. The rats were killed 4, 8 and 12 h after injection, the brains, hearts, spleens and adrenals removed and analysed for adrenaline, noradrenaline, metaraminol and alpha‐methyl‐m‐tyramine.

. In virtually all cases, both during rest (27° C) and sympathetic stress (4° C), treatment of the rats with alpha‐methyl‐p‐tyrosine methyl ester increased the amount of metaraminol formed from alpha‐methyl‐m‐tyrosine. The only organ not containing increased quantities of metaraminol in the presence of alpha‐methyl‐p‐tyrosine methyl ester was the adrenals, taken from the rats kept at 27° C. Adrenals removed from the cold‐exposed rats contained more metaraminol when alpha‐methyl‐p‐tyrosine methyl ester was combined with alpha‐methyl‐m‐tyrosine than when alpha‐methyl‐m‐tyrosine was used alone.

. These results demonstrate that the inhibition of noradrenaline synthesis, by treatment with the tyrosine hydroxylase inhibitor alpha‐methyl‐p‐tyrosine methyl ester, increased the conversion of alpha‐methyl‐m‐tyrosine to metaraminol. It is concluded that inhibiting the formation of dopa allowed increased amounts of alpha‐methyl‐m‐tyrosine to enter the biosynthetic pathway. These results support the false sympathetic transmitter concept advanced for metaraminol.
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

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

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

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

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

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

. 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

. 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

. 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

. 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

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

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

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

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

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.
Regional and subcellular changes in the concentration of 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid in the rat brain caused by hydrocortisone, DL‐α‐methyltryptophan l‐kynurenine and immobilization
Authors: CURZON G. , GREEN A. R.
Published: July 2012

In agreement with previous findings on whole brain, the intraperitoneal injection of hydrocortisone, DL‐α‐methyltryptophan or l‐kynurenine decreased the concentrations of 5‐hydroxytryptamine (5‐HT) and 5‐hydroxyindoleacetic acid (5‐HIAA) in different regions of the rat brain.

Hydrocortisone caused similar decreases in the concentrations of both 5‐HT and 5‐HIAA, suggesting decreased 5‐HT synthesis.

Changes in the concentration of 5‐HIAA after hydrocortisone corresponded significantly to those after α‐methyltryptophan. Changes in the concentration of 5‐HT did not correspond, possibly due to falsely high 5‐HT values because of interfering material derived from α‐methyltryptophan.

In general, kynurenine caused larger decreases in the concentration of 5‐HT than in the concentration of 5‐HIAA.

In agreement with previous findings with whole brain, immobilization of rats for 5 h decreased the concentration of 5‐HT and increased that of 5‐HIAA in most brain regions.

The order of the percentage decreases in the concentrations of 5‐HIAA 6 h after hydrocortisone injection was, in decreasing order: hypothalamus, striatum, cerebellum, mid‐brain, pons + medulla and cortex. The percentage increases after immobilization for 5 h were in the reverse order.

The differences between the percentage decreases in the concentration of 5‐HIAA after hydrocortisone and the percentage increases after immobilization were very similar in all regions except the hypothalamus. This is consistent with immobilization stress increasing the firing rate of 5‐hydroxytryptaminergic neurones similarly in different regions.

During the first 3 h of immobilization the concentrations of 5‐HIAA in the hypothalamus and in the rest of the brain increased approximately in parallel. Between 3 and 5 h, 5‐HIAA returned to control concentrations in the hypothalamus while continuing to rise in the rest of the brain.

Relative changes in the concentration of 5‐HT in particulate and supernatant fractions after the various treatments were comparable except 2 h after kynurenine injection when the concentration of 5‐HT fell in the particulate but not in the supernatant fraction. The concentration of 5‐HT did fall in the latter, though more slowly than in the former fraction, suggesting a concentration of amine synthesizing organelles in particulate material.
Selective blockade of the vasodepressor response to prostaglandin F2α in the anaesthetized rabbit
Authors: LEVY B. , LINDNER H. R.
Published: July 2012

The prostaglandin‐blocking activity of meclofenamic acid, N‐(2,6‐dichloro‐m‐tolyl)anthranilic acid (CI‐583), was analysed in the anaesthetized rabbit. PGF2α, PGE1 and isoprenaline were injected before and after meclofenamic acid infusion.

Isoprenaline produced a fall in blood pressure, a reduction in oviduct motility and a reduction in uterine motility if the uterus showed marked spontaneous motility. PGF2α uniformly produced a fall in blood pressure and an increase in both uterine and oviduct contractility. PGE1 produced a fall in blood pressure, a reduction in oviduct motility and no consistent effect on uterine motility.

Meclofenamic acid selectively blocked the vasodepressor response to PGF2α. The vasodepressor responses to PGE1 and isoprenaline as well as the effects of all three agonists on uterine and oviduct contractility were not reduced by treatment with meclofenamic acid.

Polyphloretin phosphate (PPP) administered to two rabbits in a cumulative dose of 94 mg/kg showed no significant blocking action on the vasodepressor or uterine and oviduct contractor responses to PGE1 or PGF2α though this compound, like meclofenamic acid, has been reported to antagonize the actions of PGE1 and PGF2α on isolated smooth muscle preparations.
Effect of dopamine on pancreatic secretion in the dog
Authors: HASHIMOTO K. , SATOH S. , TAKEUCHI O.
Published: July 2012

Effects of l‐dopa and dopamine on the secretion of pancreatic juice were investigated in preparations of the isolated blood‐perfused canine pancreas.

Dopamine (1–10 μg) given intra‐arterially caused a profuse flow of juice.

The secretory activity of dopamine (3 μg) was approximately equal to that of secretin (0·1 unit).

l‐Dopa (10–100 μg) given by a single intra‐arterial injection was ineffective, but infusion at 100 μg/min for 10 min caused a marked increase of secretion after a delay of a few minutes.

Intravenous administration of either l‐dopa (3 mg/kg) or dopamine (10–100 μg/kg) elicited a marked increase of pancreatic secretion, but was definitely less effective than intra‐arterial injection.

Dopamine‐induced secretion was not modified by atropine, phentolamine, propranolol, guanethidine or tetrodotoxin.

It is concluded that dopamine acts directly on the exocrine cells in the pancreas.
Kallikrein, trypsin‐like proteases and amylase in mammalian submaxillary glands
Authors: BHOOLA K. D. , DOREY GUNDULA
Published: July 2012

The tissue concentration of kallikrein, trypsin‐like proteases and amylase has been determined in the submaxillary glands of the cat, dog, rabbit, rat, hamster and guinea‐pig.

Submaxillary gland extracts of the six species showed a wide variation in kallikrein content. The esterase activity in the extracts, however, did not correlate with the kininogenase activity of kallikrein. Both activities in each of the six species were affected by proteinase inhibitors but not in the same way.

Evidence is presented which indicates that trypsin‐like proteases similar to those described in the rat, also occur in the hamster and cat submaxillary glands.

An even greater spread of amylase activity was observed between the species.

The assumption that mammalian submaxillary kallikreins are identical proteins is questioned.
Effect of inhibition of catecholamine synthesis on central catecholamine‐containing neurones in the developing albino rat
Authors: LOIZOU L. A.
Published: July 2012

Tyrosine hydroxylase is thought to be the rate limiting enzyme step in catecholamine biosynthesis. Inhibition of this enzyme using α‐methyl‐p‐tyrosine resulted in a time dependent depletion (and repletion) of formaldehyde induced fluorescence in catecholamine‐containing neurones of the central nervous system in developing and adult rats.

Dopamine‐containing neurones were depleted faster and more completely than noradrenaline‐containing neurones.

The extent of depletion caused by α‐methyl‐p‐tyrosine in the initial 6–9 h period was more or less comparable in young and adult rats from the age of 1 week onwards; this suggests that catecholamine turnover increases with age and parallels the increase in catecholamine levels.

The extent of depletion (and repletion) 18 h after administration of the inhibitor varied in animals of different age.

Administration of a monoamine oxidase inhibitor just before administration of α‐methyl‐p‐tyrosine resulted in a reduction of the extent of depletion caused by the latter drug, indicating that monoamine oxidase is important for the breakdown of catecholamines in rats of all ages.

It is suggested that the catecholamine‐containing neurones of the newborn are biochemically as well as functionally differentiated before completion of morphological differentiation.
Effect of aminoguanidine, chlorpromazine and NSD‐1055 on gastric secretion and ulceration in the Shay rat
Authors: Radwan A. G. , West G. B.
Published: July 2012

Both chlorpromazine and NSD‐1055 (a non‐steroidal anti‐inflammatory drug) markedly lower the volume and acidity of gastric contents of rats subjected to pyloric ligation (Shay technique) and reduce the degree of ulceration in the stomach. On the other hand, aminoguanidine (an inhibitor of histaminase) has no effect on acid secretion or ulceration in these animals.
Control of pancreatic amylase release in vitro: effects of ions, cyclic AMP, and colchicine
Authors: BENZ L. , ECKSTEIN B. , MATTHEWS E. K. , WILLIAMS J. A.
Published: July 2012

. The time course and concentration‐response relationship of amylase release from pieces of guinea‐pig pancreas in vitro in response to bethanechol and pancreozymin was determined.

. Removal of Ca++ from the medium had no effect on basal amylase release but abolished the stimulating effect on release of bethanechol.

. Elevation of the concentration of Mg++ in the medium increased basal amylase release and reduced the response to bethanechol.

. Elevation of the concentration of K+ in the medium increased amylase release; this effect was blocked by a concentration of atropine which blocked also the response to bethanechol.

. Cyclic AMP, dibutyryl cyclic AMP and theophylline failed to stimulate amylase release. Pancreatic cyclic AMP concentrations were found not to be increased by bethanechol, pancreozymin or an elevated concentration of K+ in the medium.

. Colchicine had no effect on basal amylase release or the response to bethanechol or pancreozymin.

. It is concluded that the coupling of stimulus to secretion involves ionic control but that neither cyclic AMP production nor microtubular mechanisms play a major role in controlling exocytosis in the pancreatic acinar cell. These findings are discussed in relation to the stimulus‐secretion coupling processes in other cells.
Anaesthetic, cardiovascular and respiratory effects of a new steroidal agent CT 1341: a comparison with other intravenous anaesthetic drugs in the unrestrained cat
Authors: CHILD K. J. , DAVIS B. , DODDS M. G. , TWISSELL D. J.
Published: July 2012

. The anaesthetic, cardiovascular, respiratory and adverse effects produced by the intravenous injection of CT 1341, thiopentone, methohexitone, pentobarbitone, propanidid and ketamine have been compared in unrestrained cats prepared with chronically implanted venous and arterial cannulae. Aortic blood pressure and heart rates were monitored before, during and after loss of consciousness.

. CT 1341 produced rapid induction of anaesthesia followed by moderately rapid recovery, was active over a wide range of doses and caused minimal respiratory depression and few adverse effects. It caused an initial short‐lasting tachycardia and fall in aortic blood pressure succeeded by a secondary depressor response.

. The safety margin was narrower with the barbiturate drugs than with CT 1341, and large doses induced apnoea and respiratory depression. Small doses of methohexitone elicited excitatory effects and large doses caused severe respiratory and circulatory depression, and recovery from anaesthesia was protracted.

. Propanidid induced short‐lasting light anaesthesia. The safety margin was narrowest with this drug and induction was associated with adverse circulatory, respiratory and other effects.

. Ketamine was active over a wide range of doses but exhibited qualitatively different properties from the other anaesthetics. Induction was slower after small doses and these produced circulatory stimulation, catatonia and bizarre behavioural effects. Large doses caused respiratory and circulatory depression and recovery was protracted.

. It is concluded that CT 1341 has a wider therapeutic latitude, produces less respiratory depression and has other advantages over the currently used intravenous anaesthetics.
A comparison of the excitatory and inhibitory effects of non‐adrenergic, non‐cholinergic nerve stimulation and exogenously applied ATP on a variety of smooth muscle preparations from different vertebrate species
Authors: BURNSTOCK G. , SATCHELL D. G. , SMYTHE ANNE
Published: July 2012

. The responses to non‐adrenergic, non‐cholinergic nerve stimulation have been compared with those to exogenously applied ATP on seventeen different tissues from a number of vertebrate classes.

. Stimulation of all the mammalian gut preparations studied (with the exception of the guinea‐pig ileum) after blockade of the effects of adrenergic and cholinergic nerve stimulation by guanethidine (3·5 μm) and hyoscine (1–3 μm) caused inhibition; exogenously applied ATP mimicked this inhibitory response.

. Stimulation of the guinea‐pig ileum in the presence of hyoscine and guanethidine, usually caused a diphasic response, relaxation followed by contraction; exogenously applied ATP mimicked this response, in contrast to acetylcholine and noradrenaline which caused excitation and relaxation respectively.

. Stimulation of preparations of lower vertebrate gut and guinea‐pig bladder in the presence of hyoscine and guanethidine caused contraction; exogenously applied ATP mimicked this contractile response.

. In each preparation the time course of the response to ATP was similar or identical to the response to non‐adrenergic, non‐cholinergic nerve stimulation.

. The results are consistent with the hypothesis that a purine nucleotide may be the transmitter substance released from non‐adrenergic, non‐cholinergic nerves supplying smooth muscle preparations from a number of vertebrate classes.
Effect of external lymph drainage and of coumarin treatment on thermal injury in the rat hind leg
Authors: FÖLDI‐BÖRCSÖK ETHEL
Published: July 2012

. External lymph drainage brings about a significant protective effect in thermal oedema of the rat hind leg. It is suggested that external lymph drainage prevents vasoactive substances drained from the site of injury from passing into the blood stream, which would further increase permeability of the injured blood capillaries.

. Coumarin (5,6‐benzo‐alpha‐pyron) brings about a significant protective effect against the same injury in sham‐operated rats.

. The strongest protective effect may be attained by combining external lymph drainage with the administration of coumarin.

. The additional therapeutic effect brought about by coumarin treatment in rats with external lymph drainage is not mediated by an increased flow. The possible mechanisms are discussed.
Pharmacokinetic and toxicological studies of antimony dextran glycoside (RL‐712)
Authors: CASALS J. BOU
Published: July 2012

. The absorption, tissue distribution and excretion of antimony dextran glycoside (RL‐712) has been studied in normal rodents.

. Some organs in the body, especially liver and spleen, retain large amounts of antimony for considerable periods of time. Excretion of antimony in the urine was low and only about 10–12% of the dose administered was excreted within the first 48 hours.

. Blood levels were maintained for at least 3 days after a single intramuscular dose to rabbits, corresponding to 14 mg Sb/kg body weight.

. Toxicity studies and tests on foetal toxicity in mice and rats, respectively, showed no abnormalities.

. The possible value of RL‐712 in the prophylaxis and treatment of leishmaniasis is discussed.
Acceleration of catecholamine biosynthesis in sympathetically innervated tissues by angiotensin‐II‐amide
Authors: BOADLE‐BIBER MARGARET C. , HUGHES J. , ROTH R. H.
Published: July 2012

. The effect of angiotensin‐II‐amide on the biosynthesis of catecholamines (CA) has been studied in a number of isolated tissues in vitro.

. Angiotensin increased the synthesis of CA from 14C‐tyrosine in guinea‐pig atria and portal vein, in rat vasa deferentia and the rabbit portal vein.

. Angiotensin had no effect on synthesis of CA from 14C‐labelled dl‐DOPA.

. The conditions required to demonstrate an increased synthesis were critical with respect to incubation time and angiotensin concentration. Effects were most readily apparent after incubation for 1 h with concentrations of angiotensin ranging from 10−9 to 10−7m. Higher concentrations caused a significant reduction in synthesis.

. An increased release of newly synthesized CA into the incubation medium was sometimes seen in the presence of angiotensin. However, there was no correlation between increased synthesis and release of CA.

. Angiotensin was rapidly destroyed when incubated with guinea‐pig or rat tissues in Krebs solution. The increase in CA synthesis was only apparent at a time when the incubation medium could have contained only a fraction of the original angiotensin activity.

. It is concluded that the effect of angiotensin is not due to increased release of noradrenaline (NA) or to inhibition of NA uptake into nerves. It is possible that angiotensin may influence the activity of tyrosine hydroxylase or its cofactors by an as yet unknown mechanism.
Inhibition of catecholamine uptake in the isolated rat heart by haloalkylamines related to phenoxybenzamine
Authors: IVERSEN L. L. , SALT P. J. , WILSON H. A.
Published: July 2012

. Twenty‐one haloalkylamine derivatives were tested as inhibitors of both the neuronal uptake of 3H‐noradrenaline (NA) by the Uptake1 mechanism and the extraneuronal uptake of 3H‐NA by the Uptake2 mechanism in the isolated rat heart.

. At a concentration of 50 μm most of the compounds tested caused a significant inhibition of both uptake processes, although there were wide differences in the relative effects on Uptake1 and Uptake2. Some tentative structure activity relationships for uptake inhibition were formulated from these results.

. Phenoxybenzamine was confirmed to be a potent inhibitor of both the Uptake2 and Uptake1 mechanisms, with IC50 values for these two systems of 2·8 μm and 0·9 μm respectively.

. The substances N‐(9‐fluorenyl)‐N‐methyl‐β‐chloroethylamine (SKF 550), N‐(3,4‐dimethoxyphenylisopropyl)‐N‐benzyl‐β‐chloroethylamine (SKF 625A) and N‐(4‐methoxyphenoxyisopropyl)‐N‐benzyl‐β‐chloroethylamine (SKF 784A) were significantly more potent than phenoxybenzamine as Uptake2 inhibitors, and were all less potent than phenoxybenzamine as Uptake1 inhibitors. The compound SKF 550 is the most potent and selective inhibitor of Uptake2 so far described. It has an IC50 for Uptake2 of 008 μm, and an IC50 for Uptake1 of approximately 400 μm.

. Comparison of the present results with the known activities of these blocking agents suggests that no correlation exists between adrenoceptor blocking activity and ability of the substances to act as inhibitors of Uptake2 or Uptake1.