bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of noradrenaline, other sympathomimetic amines and antagonists on neurones in the brain stem of the cat
Authors: BOAKES R. J. , BRADLEY P. B. , BROOKES N. , CANDY J. M. , WOLSTENCROFT J. H. 
Published: July 2012

Summary
The effects of (–)‐noradrenaline ((–)‐NA) and related compounds on brain stem neurones in decerebrate unanaesthetized cats have been investigated using the technique of iontophoretic application from micropipettes.
Four types of response to (–)‐NA have been described. These were short lasting inhibition, long lasting inhibition, excitation, and a biphasic response consisting of short lasting inhibition followed by excitation. A variable amount of desensitization of the excitatory response, but not of inhibitory responses, was observed.
Experiments in which small currents were used to pass (–)‐NA from pipettes with smaller tips did not lead to any appreciable change in the proportions of neurones excited or inhibited.
A variety of sympathomimetic agonists was tested. Short lasting inhibition was less sensitive than excitation to changes in molecular structure. Long lasting inhibition was more sensitive to molecular change and was not mimicked by some of the agonists which mimicked short lasting inhibition.
Although agonists without one ring hydroxyl had weaker effects than those with both, compounds in which both ring hydroxyl groups were absent (β‐hydroxyphenylethylamine, ephedrine and amphetamine) mimicked excitation strongly. It is possible that the compounds without both ring hydroxyl groups had some effect other than simple agonistic activity.
A dissociation was observed between responses to dopamine and (–)‐NA. p‐Tyramine mimicked dopamine, rather than (–)‐NA.
Neither the α‐agonist, phenylephrine nor the β‐agonist, isoprenaline mimicked neuronal responses to (–)‐NA. The α‐antagonists phentolamine and phenoxybenzamine and the β‐antagonists dichloroisoprenaline, propranolol and d(–)‐INPEA and combinations of propranolol with phentolamine or phenoxybenzamine were ineffective in blocking either excitation or inhibition. Thus, the central receptors appear to be different from peripheral α‐ and β‐receptors.
The most effective antagonist of excitation was (–)‐α‐methylnoradrenaline. Metaraminol and dihydroergotamine also had some antagonistic activity. None of the compounds tested blocked inhibition. The effects of (–)‐α‐methylnoradrenaline have been discussed in relation to the hypotensive action of α‐methyldopa.
Distribution kinetics and intestinal absorption of practolol in the rat
Authors: BARBER H. E. , BOURNE G. R. 
Published: July 2012

Summary
After intravenous injection of practolol the blood concentration‐time curve is fitted by a bi‐exponential function. A two compartment open system model is therefore a minimal requirement in order to describe adequately the distribution of the drug in the body.
The parameters of the two compartment model for practolol were determined. The mean values for the ‘fast disposition’ half life and the ‘slow disposition’ half life were 0.5 min and 13.3 min, respectively.
The rate constants of distribution and elimination were similar in different animals. The volume of the central compartment was related to the weight of the animal.
The absorption of practolol from an intestinal site was measured by its appearance in the blood. The rate constant for this process was estimated to be 0.03 min−1.
Mechanism of the inhibitory action of indomethacin on smooth muscle
Authors: NORTHOVER B. J. 
Published: July 2012

Summary
Strips of muscle from the wall of the guinea‐pig stomach contracted in response to electrical field stimulation (100 ms pulses, 0.2 Hz) or to histamine (1 μg/ml), and these responses were inhibited by indomethacin (2–20 mg/100 ml).
Glycerol‐extracted strips of stomach muscle developed tension when exposed to a mixture of ATP, CP, magnesium chloride and calcium chloride. The tension response was not altered by indomethacin (50 mg/100 ml).
Indomethacin failed to alter the content of ATP or of CP in strips of stomach muscle.
The calcium content of strips of stomach muscle increased in response to 30 min of electrical stimulation (100 ms pulses, 0.2 Hz). The uptake of calcium and the contraction of the strips were inhibited by indomethacin (2–20 mg/100 ml) to a similar extent.
Calcium uptake by electrically stimulated guinea‐pig aorta was inhibited by lower concentrations of indomethacin than were required by stomach muscle.
Effect of amphetamine on the transmission of repetitive impulses through the isolated superior cervical ganglion of the rat
Authors: DOWNING O. A. 
Published: July 2012

Summary
The cervical sympathetic trunk of the isolated rat superior cervical ganglion was stimulated with short bursts of repetitive pulses. At room temperature with rates of stimulation of 4 Hz and above, the ganglionic action potentials were reduced in size.
Amphetamine (2·7 × 10−5m), which caused some depression of transmission during stimulation at 0·1 Hz, caused a partial reversal of the depression of transmission occurring with rates of stimulation above 4 Hz.
This action of amphetamine was mimicked by adrenaline (3 × 10−5m) and noradrenaline (9·6 × 10−5m) but not by isoprenaline (1·8 × 10−5m) and was unaffected by propranolol (1·4 × 10−5m) but was abolished by prior application of phenoxybenzamine (5·8 × 10−6m). Furthermore, this action of amphetamine was unaltered in ganglia taken from rats pretreated with reserpine (single dose of 6 mg/kg, 16 h before dissection).
Amphetamine had no effect on the surface potentials of the ganglion or on changes in these potentials produced by concentrations of carbachol (5·5 × 10−6m to 5·5 × 10−3m).
It is concluded that amphetamine has a direct action on α‐adrenoceptors situated at presynaptic sites.
Binding of bromosulphthalein sodium by human serum albumin using a continuous diafiltration technique
Authors: CRAWFORD J. S. , JONES R. L. , THOMPSON J. M. , WELLS W. D. E. 
Published: July 2012

Summary
The recently introduced ultrafiltration‐cum‐dialysis technique termed continuous diafiltration has been used to obtain detailed binding isotherms of equilibrium solution concentration of bromosulphthalein (BSP) versus the number of molecules of BSP bound per molecule of human serum albumin for pure human serum albumin solutions (albumin concentrations: 1·59–3·39 g/100 ml) and for three dilutions of pooled human serum (albumin concentrations: 1·45–2·85 g/100 ml) in 310 ideal milliosmolar phosphate buffer at pH 7·4 and 22° C.
Qualitative analysis of the isotherms seems to indicate that there is a competition between the polymerization of the albumin to dimers and high oligomers and the binding of BSP by albumin.
The binding capacity of pure human serum albumin at total BSP (bound and free) concentrations below 2·3 mm is greater than that of the pooled serum at an equivalent albumin concentration, possibly indicating the blockage of binding sites by more strongly binding ligands.
The binding capacity of pure albumin at total BSP concentrations greater than 2·3 mm is less than that of pooled serum at an equivalent albumin concentration, suggesting the presence of other non‐ultrafilterable materials in the serum capable of binding BSP.
Relative activities on and uptake by human blood platelets of 5‐hydroxytryptamine and several analogues
Authors: BORN G. V. R. , JUENGJAROEN KANCHANA , MICHAL F. 
Published: July 2012

Summary
The specificity of platelet receptor sites for 5‐HT uptake and for the rapid morphological change and aggregation was investigated with 5‐hydroxytryptamine (5‐HT) and seventeen analogues as well as with some antagonists of 5‐HT.
The analogues, with the exception of 5‐hydroxy‐N'N'‐dibutyltryptamine, caused the rapid morphological change in platelets. In concentrations below those needed to produce the agonistic action (viz. 0·05–2·0 μm), these analogues themselves inhibited competitively the shape change caused by 5‐HT.
The velocity of change in shape caused by 5‐HT was reduced in low Na media.
Ten analogues produced platelet aggregation; three of these, viz. 5‐methoxy‐α‐methyltryptamine, 5‐hydroxy‐α‐methyltryptamine and 5‐hydroxy‐N'N'‐diisopropyltryptamine), were approximately equipotent with 5‐HT. Six analogues did not induce platelet aggregation.
All the analogues which prevented the initial change in shape of platelets caused by 5‐HT also inhibited its aggregating effect, apparently competitively with low Ki values (0·02–1·6 μm).
As with the inhibition of shape change, the inhibition of aggregation shows relatively low structural specificity of the receptor site.
Methysergide was a potent inhibitor of shape change and aggregation (Ki˜0·03 μm); imipramine was much less inhibitory (Ki˜5–10μm).
Only one analogue (5‐hydroxy‐α‐methyltryptamine) was taken up like 5‐HT by platelets. All the other analogues inhibited the uptake of 5‐HT by platelets (Ki = 0·2–2·7 μm).
Methysergide was a weak inhibitor of 5‐HT uptake (Ki˜125 μm) whereas imipramine was very effective (Ki˜0·3 μm).
Our results show that the initial change in shape of platelets is required for and precedes aggregation. The structural specificity of the platelet receptor concerned with shape change and aggregation caused by 5‐HT appears low whereas the uptake mechanism is a highly specific one. The uptake probably proceeds through more than one step, the relationship between the steps is not yet clear.
Effects of infusions of catecholamines, angiotensin, vasopressin and histamine on hepatic blood volume in the anaesthetized cat
Authors: GREENWAY C. V. , LAUTT W. W. 
Published: July 2012

Summary
Hepatic volume was recorded by a plethysmographic technique in cats anaesthetized with pentobarbitone; the hepatic artery and portal vein remained intact. Dose‐response curves were obtained for intravenous infusions of adrenaline, noradrenaline, angiotensin, vasopressin and histamine.
Adrenaline and noradrenaline decreased hepatic blood volume and did not differ significantly in potency. Up to 40% of the hepatic blood volume was expelled by doses within the range secreted by the adrenal medullae.
Isoprenaline, infused into the hepatic artery, had no significant effect on hepatic blood volume in doses which caused maximal vasodilatation of the hepatic arterial bed. Relaxation of hepatic capacitance vessels mediated by β‐adrenoceptors did not occur.
Angiotensin infusions in doses previously shown to cause intestinal and splenic vasoconstriction, decreased hepatic blood volume and on a molar or microgramme basis, angiotensin was the most potent of the agents tested. Doses within the probable physiological range of endogenous production decreased hepatic blood volume by up to 20%. The responses were not significantly different when the hepatic nerves were intact or sectioned.
Vasopressin infusions produced only small decreases in hepatic blood volume. Doses within the range secreted by the posterior pituitary which constrict the intestinal and splenic resistance vessels, did not decrease hepatic blood volume by more than 10%.
Histamine produced no change in hepatic blood volume in doses which readily produce outflow block in dogs. Either the specific hepatic venous smooth muscle involved in outflow block is absent in the cat or it has no histamine receptors.
After the rapid change in hepatic blood volume at the onset of the infusion, hepatic volume remained steady for the duration of each infusion. There was no evidence that these agents caused net transsinusoidal fluid movements.
Selective inhibition of angiotensin pressor responses in the pithed rat by tetraethylthiuram disulphide (disulfiram) and sodium diethyldithiocarbamate (DDC)
Authors: DAY M. D. , HALL J. M. , OWEN D. A. A. 
Published: July 2012

Summary
Pressor responses to sympathetic outflow stimulation, noradrenaline and angiotensin have been recorded in pithed rats.
Disulfiram (50 mg/kg) and sodium diethyldithiocarbamate (DDC) (5–100 mg/kg) both caused an initial increase in the pressor response to all three procedures followed by a selective inhibition of the angiotensin responses.
Penicillamine (1–100 mg/kg) and ascorbic acid (1–500 mg/kg) increased the pressor responses to all three procedures without any subsequent blocking action.
Reserpine (5 mg/kg daily for 3 days) abolished responses to sympathetic outflow stimulation but did not impair angiotensin or noradrenaline responses.
In reserpinized rats, the initial enhancement of angiotensin responses after disulfiram and sodium diethyldithiocarbamate was absent or reduced and the onset of the subsequent block was accelerated.
Possible mechanisms for the angiotensin‐blocking action of disulfiram and sodium diethyldithiocarbamate are discussed.
Effect of sympathomimetic drugs in eliciting hypertensive responses to reserpine in the rat, after pretreatment with monoamineoxidase inhibitors
Authors: CASHIN C. H. 
Published: July 2012

Summary
The effects of some rapidly metabolized sympathomimetic amines, such as β‐phenylethylamine and p‐tyramine, in eliciting hypertensive responses to reserpine in the anaesthetized rat, have been studied.
Retardation of metabolism, by pretreatment with the monoamineoxidase inhibitors iproniazid or phenelzine, causes β‐phenylethylamine (which in untreated rats has no effect) to induce hypertensive responses to reserpine. Tyramine and other hydroxy substituted phenylethylamines are much less active in this respect, probably because of relatively poor lipid solubility.
Hypertensive responses to reserpine are due to catecholamine release, which is believed to be from stores made accessible to indirectly acting sympathomimetic amines with high lipid solubility by an action of reserpine on cell membranes.
Nature of the calcium dependent potassium leak induced by (+)‐propranolol, and its possible relevance to the drug's antiarrhythmic effect
Authors: GLYNN I. M. , WARNER ANNE E. 
Published: July 2012

Summary
Manninen (1970) recently reported that in the presence of calcium ions, (+)‐propranolol causes a massive loss of potassium ions from human red cells, together with a marked inward ‘counter‐transport’ of potassium ions from the medium.
This paper shows, theoretically, that counter‐transport of the kind he observed may be accounted for by the setting up of a diffusion potential across the cell membrane and does not imply that, under the influence of propranolol, potassium ions cross the membrane by some process other than free diffusion.
The physiological and pharmacological significance of this interpretation of Manninen's findings is briefly discussed.
Metabolism of amylobarbitone in patients with chronic liver disease
Authors: MAWER G. E. , MILLER N. E. , TURNBERG L. A. 
Published: July 2012

Summary
A single dose of amylobarbitone (3·23 mg/kg) was given by intravenous injection to each of ten healthy controls and two groups of five patients with chronic liver disease. A curve of serum amylobarbitone concentration against time was prepared for each subject and the proportion of the serum amylobarbitone bound to protein determined. The urinary excretion of the metabolite hydroxyamylobarbitone, ethyl (3 hydroxyisoamyl) barbituric acid was measured.
The degree of protein binding of serum amylobarbitone was reduced in the five patients (group I) with abnormally low concentrations of albumin in serum (<3·5 g/100 ml) but was normal in the five patients (group II) with normal serum albumin concentrations (>3·5 g/100 ml).
The equation for a double exponential decay was fitted to the concentration/time curves for amylobarbitone free in the serum water. The mean intercepts and rate constants were used to calculate the dimensions of mathematical models based on a two compartment open system.
The five patients (group I) who had abnormally low concentrations of albumin in serum showed impairment of amylobarbitone metabolism; the rate constant β(h−1) for the second exponential decay of serum amylobarbitone concentration was reduced (P<0·01), the urinary excretion of hydroxyamylobarbitone was reduced (P<0·001) and the mean serum water clearance (Ce ml/min) representing amylobarbitone elimination by metabolism was reduced.
The five patients (group II) who had normal concentrations of albumin in serum showed no impairment of amylobarbitone metabolism. Within the total patient group there were strong and significant positive correlations between the serum albumin concentration and each of the indices of the rate of amylobarbitone metabolism.
Both patient groups showed an increase in the first dispositional rate constant α(h−1) and in the clearance (Ct ml/min) representing transfer between central and peripheral compartments. The physiological basis for this observation is uncertain.
The clinical response to the single intravenous dose of amylobarbitone was not significantly greater (P=0·11) in the patient group (I) with slow amylobarbitone metabolism than in the patient group (II) with a normal rate of amylobarbitone metabolism.
Pharmacology of o‐chlorobenzylidene malononitrile (CS)
Authors: BRIMBLECOMBE R. W. , GREEN D. M. , MUIR A. W. 
Published: July 2012

Summary
The effects of o‐chlorobenzylidene malononitrile (CS) have been studied on several isolated organs and tissues, anaesthetized animals and cat encéphale isolé preparations.
On the isolated guinea‐pig ileum an initial dose of CS produced a small, non‐maintained contraction. Subsequent doses had reduced effects. There was no effect on peristalsis when the substance was given intraluminally.
No significant effects of CS were detected on the rat phrenic nerve‐diaphragm preparation, the isolated perfused rabbit heart or on the contractor response of the indirectly stimulated cat tibialis muscle.
In the cat encéphale isolé preparation 1 mg/kg (i.v.) produced a brief period of electrocortical alerting but no abnormal activity in the electrocorticogram. Doses in excess of 10 mg/kg produced cortical depression.
Intravascular injection into the chloralose anaesthetized cat resulted typically in a pressor response accompanied by a brief period of apnoea. The threshold dose for the pressor response varied with the route of administration, but generally lay between 2·5 and 12·5 μg/kg; the threshold dose for apnoea was slightly higher. Small variations in this pattern of response were seen with different species and other anaesthetics.
When administered by stomach tube to chloralose anaesthetized cats, CS produced no measurable effects at doses of up to 100 mg/kg.
No changes in blood pressure or respiration were detected in anaesthetized cats given pure CS aerosol for 1 h in concentrations of between 345 mg/m3 and 1·39 g/m3 via a tracheal cannula or through the upper respiratory tract. Pure CS solution given by slow intravenous infusion at a similar dose and over a similar period produced significant effects on blood pressure and respiration.
Pyrotechnically generated (grenade) CS produced variable effects when given by inhalation in concentrations of between 460 and 1,040 mg/m3 for 1 hour. Respiratory depression, possibly reflex in nature, regularly occurred when the material was given via the upper respiratory tract, and respiratory stimulation occurred when it was given via a tracheal cannula.
Some cats were pre‐exposed to a dose of 500 (mg/min)/m3 on 4 successive days and on the fifth day anaesthetized and exposed to high concentrations of grenade CS. Three out of six cats died during or after this final exposure compared to one out of six among animals not so pre‐exposed. The general pattern of response to the final exposure to CS in the two groups was similar.
The physiological disposition of 14C‐methsuximide in the rat
Authors: NICHOLLS P. J. , ORTON T. C. 
Published: July 2012

Summary
. 14C‐Methsuximide (N‐methyl‐14C‐2‐methyl‐2‐phenylsuccinimide) was rapidly absorbed from the small intestine of the rat (t½ 17·4 min).
. The drug was rapidly and fairly evenly distributed throughout the body with peak blood and tissue levels occurring 1 h after oral administration. At all times, adrenals, body fat, kidneys and liver had higher levels of 14C‐methsuximide than other tissues and the drug freely traversed the blood‐brain barrier. However, radioactivity disappeared rapidly from most tissues after the initial phase of the distribution.
. During 24 h, 26% of the orally administered radioactivity was recovered in urine and 29% appeared in expired air as 14CO2. The excretion of 14CO2 indicated N‐demethylation of 14C‐methsuximide to 2‐methyl‐2‐phenylsuccinimide. 2·7% of an administered dose of methsuximide was excreted unchanged in 24 h urine and 2·7% appeared as 2‐methyl‐2‐phenylsuccinimide. 2‐Methyl‐2‐phenylsuccinimide was also detected as a urinary metabolite of methsuximide in man.
. 2‐Methyl‐2‐phenylsuccinimide possesses anticonvulsant activity and it is suggested that this metabolite contributes to the overall anticonvulsant activity and toxicity of methsuximide.
. Rat urine also contained a radioactive substance with similar chromatographic properties to one of the products of alkaline hydrolysis of methsuximide. This compound may arise from the spontaneous decomposition of the parent drug in vivo.
Relative importance of the enzymic hydrolysis of suxamethonium in plasma and tissues: studies in Rhesus monkeys
Authors: PECK ANTHONY W. 
Published: July 2012

Summary
. Suxamethonium was given by intravenous infusion to anaesthetized Rhesus monkeys and the infusion rate required to produce after 10 min a 50% reduction in twitch tension of the indirectly stimulated gastrocnemius or tibialis anterior muscle (IR50) was calculated from results obtained with paired infusions of two concentrations, repeated at intervals. The IR50 values in three monkeys were (388, 958 and 1,010 nmol/kg)/minute.
. In one experiment the cholinesterase activity in plasma was increased to 125 and then to 182% of the initial value by infusions of purified human cholinesterase (usual enzyme). This increased the IR50 by 34 and then by 60%, respectively.
. Inhibition by iso‐OMPA of cholinesterase activity in plasma and tissues (four monkeys) by more than 90% lowered the mean IR50 value to (69 ± 11 (s.e. m.) nmol/kg)/minute. Restoration of cholinesterase activity in the plasma of these animals by infusion of purified human cholinesterase raised the IR50's to values within the normal range.
. It is concluded that in the Rhesus monkey most of the infused suxamethonium is hydrolyzed by the cholinesterase in plasma before reaching the motor endplates. This agrees with observations in man with usual cholinesterase and contrasts with experiments in the cat where the hydrolysis of suxamethonium by cholinesterase in tissues was found to be more important than the hydrolysis by cholinesterase in plasma.
The effects of isoprenaline and phenylephrine on oxygen consumption in isolated smooth muscle
Authors: WESTON A. H. 
Published: July 2012

Summary
. Simultaneous measurements of oxygen consumption and mechanical activity have been made in isolated preparations of guinea‐pig taenia coli, rabbit abdominal aorta and the longitudinal muscle of rabbit duodenum.
. Mean resting oxygen consumption was greater in mechanically‐active preparations (taenia coli and duodenum) than in the aorta which showed no spontaneous activity.
. The relaxation produced by isoprenaline in guinea‐pig taenia coli and rabbit duodenum was accompanied by a dose‐dependent fall in oxygen consumption.
. The relaxation produced by phenylephrine in guinea‐pig taenia coli was accompanied by a dose‐dependent fall in oxygen consumption whereas, in the rabbit duodenum, the transient fall in tension was not accompanied by any significant change in oxygen consumption.
. The increase in tension produced by phenylephrine in rabbit abdominal aorta was accompanied by an increase in oxygen consumption.
. Changes in mechanical activity and oxygen consumption produced by isoprenaline and phenylephrine were antagonized by propranolol and phentolamine respectively.
. It is concluded that the variations in oxygen consumption associated with spontaneous or drug‐induced mechanical changes are simple reflections of altered mechanical activity. The possibility of additional direct metabolic actions of isoprenaline and phenylephrine is discussed.