bluuebunny/crossref_metadata_2025_split huggingface dataset:
Destruction of chlorpromazine during absorption in the rat in vivo and in vitro
Authors: CURRY S. H. , D'MELLO A. , MOULD G. P. 
Published: July 2012

Summary
Concentrations of total radioactivity in plasma of rats given intravenous and oral 35S‐chlorpromazine, were similar. Concentrations of unchanged drug, however, were lower after oral doses.
Chlorpromazine circulated in solution through isolated loops of rat intestine was rapidly absorbed by the tissue. Measurements of glucose transport and histological examination indicated that the tissue was intact. In these in vitro experiments some of the chlorpromazine was converted to products, which together with unchanged drug, were partly retained in the intestinal wall and partly transferred to the serosal side of the tissue. Observations at three concentrations supported the hypothesis that transfer of unchanged drug occurred by passive diffusion.
Conversion of chlorpromazine to metabolites in the intestine in vivo, would account for the differences in concentrations of chlorpromazine and total radioactivity in plasma after oral doses.
Some observations on the estimation of 3‐methoxytyramine in brain tissue
Authors: GULDBERG H. C. , SHARMAN D. F. , TEGERDINE P. R. 
Published: July 2012

Summary
A new method for the estimation of 4‐hydroxy‐3‐methoxyphenylethylamine (3‐methoxytyramine) in brain tissue is described. This is based on the formation of a fluorescent derivative by oxidation with potassium ferricyanide in ammonium hydroxide solution.
The effects of some drugs on the concentration of 3‐methoxytyramine in the brain are reported.
The significance of changes in the striatal concentration of 3‐methoxytyramine is discussed.
Studies on prostaglandin antagonists
Authors: BENNETT A. , POSNER J. 
Published: July 2012

Summary
Three prostaglandin antagonists have been examined for their ability to block PGE2 and PGF2α on human, guinea‐pig and isolated rat gastrointestinal muscle.
7‐oxa‐13‐Prostynoic acid was either a non‐selective antagonist, or was ineffective on the tissues studied; it had marked spasmogenic activity on the rat fundus.
1‐Acetyl‐2‐(8‐chloro‐10,11‐dihydrodibenz (b,f)(1,4) oxazepine‐10‐carbonyl)hydrazine selectively antagonized the excitatory effects of PGE2 and PGF2α in guinea‐pig and rat tissues, but not in human muscle.
Polyphloretin phosphate selectively antagonized the excitatory effects of prostaglandins in both human and guinea‐pig muscle preparations, but it caused stimulation of the rat fundus.
All the antagonists lowered the tone in many tissues. They also reduced contractions caused by potassium.
None of the compounds blocked the inhibitory effect of PGE2 on intestinal circular muscle.
The implication of these results on the nature of prostaglandin receptors, and the value of each compound as a prostaglandin antagonist are discussed.
Antagonism by β‐adrenoceptor blocking agents of the antianaphylactic effect of isoprenaline
Authors: ASSEM E. S. K. , SCHILD H. O. 
Published: July 2012

Summary
β‐Adrenoceptor blocking agents antagonized the inhibitory (antianaphylactic) effect of isoprenaline on antigen‐induced histamine release in isolated, passively sensitized, human lung and actively sensitized guinea‐pig lung suggesting that the effect is exerted through β‐adrenoceptors. No antagonism was obtained with the human allergic leucocyte preparation.
The antianaphylactic effect of isoprenaline was antagonized not only by propranolol but also by the ‘selective’ β‐adrenoceptor blocking agents, practolol and butoxamine.
The classification of β‐adrenoceptors is discussed. Certain similarities between antianaphylactic and lipolytic β‐adrenoceptors are noted.
Effects of narcotic analgesics and antagonists on the in vivo release of acetylcholine from the cerebral cortex of the cat
Authors: JHAMANDAS K. , PHILLIS J. W. , PINSKY C. 
Published: July 2012

Summary
In cats under light allobarbitone anaesthesia, the effects of intravenous injections of narcotic and non‐narcotic analgesics, of a general depressant, and of narcotic antagonists were investigated on the spontaneous release of acetylcholine (ACh) from the surface of the sensorimotor cortex.
The narcotic analgesics morphine (0·1, 1·0 and 5 mg/kg), meperidine (1·0 and 2·0 mg/kg), methadone (1·0 mg/kg) and codeine (5·0 and 10·0 mg/kg) greatly reduced ACh release.
The non‐narcotic analgesics pentazocine (1·0 and 2·0 mg/kg) and propoxyphene (5·0 and 10·0 mg/kg) as well as the depressant chlorpromazine (0·25, 0·5 and 1·0 mg/kg) also greatly reduced ACh release.
Two of the three narcotic antagonists examined, levallorphan (0·1, 1·0 and 5 mg/kg) and nalorphine (1·0 mg/kg) had the property of reducing ACh release. They were thus partial agonists. With levallorphan the greatest reduction occurred with the smallest dose injected and the effect was regularly obtained, whereas with nalorphine a reduction was obtained in some experiments only. The third, naloxone, was a specific narcotic antagonist and did not reduce the ACh release in any dose (0·01, 0·1, 0·5 and 1·0 mg/kg) examined. In a dose of 1·0 mg/kg it actually produced a small increase in Ach release.
Naloxone (0·1–1·0 mg/kg) restored the reduction in ACh release produced by the narcotic analgesics and by the partial agonist levallorphan. It partially restored the reduction produced by the non‐narcotic analgesics and by nalorphine, but had no effect on the reduction produced by chlorpromazine.
The relevance of these results with regard to analgesia and to the narcotic abstinence syndrome is discussed.
Biliary excretion of barbiturates
Authors: KLAASSEN C. D. 
Published: July 2012

Summary
Pentobarbitone and phenobarbitone are excreted into the bile of rats.
The concentration of pentobarbitone and/or its metabolites in the bile is 22‐fold higher than in the plasma; the concentration of phenobarbitone and/or its metabolites in bile is 10‐fold higher than in the plasma.
Probenecid decreases the excretion of the barbiturates into the bile.
Twenty‐eight per cent of a 35 mg/kg dose of pentobarbitone and 18% of a 75 mg/kg dose of phenobarbitone is excreted in the bile in 6 hours.
Most of the pentobarbitone and phenobarbitone excreted into the bile is not in the form of the parent compound but rather as a more polar metabolite or metabolites.
Comparison of human serum, parotid and mixed saliva levels of phenoxymethylpenicillin, ampicillin, cloxacillin and cephalexin
Authors: SPEIRS C. F. , STENHOUSE D. , STEPHEN K. W. , WALLACE EDITH T. 
Published: July 2012

Summary
A study has been made of serum, mixed and parotid salivary levels attained in normal volunteers following oral dosage of 500 mg phenoxymethylpenicillin tablets, 500 mg crushed phenoxymethylpenicillin tablets in capsules, 500 mg ampicillin, 500 mg cloxacillin and 500 mg cephalexin.
High mixed saliva levels were obtained with phenoxymethylpenicillin tablets and it is considered that these were due to rapid intra‐oral dissolution of surface powder from friable tablets. No saliva levels were detected when tablets from the same batch were put into capsules.
Low or no saliva levels were achieved with ampicillin, cloxacillin and cephalexin.
The mode of action of antibiotics in oral infections is discussed.
Effects of some sympathomimetic drugs and their antagonists on afterdischarges elicited in chronically isolated slabs of cerebral cortex
Authors: KRIP G. , VÁZQUEZ J. 
Published: July 2012

Summary
The role of sympathomimetic agents in the maintenance and termination of induced cortical epileptiform activity was studied in chronically neuronally isolated slabs of cerebral cortex in the suprasylvian gyrus of unanaesthetized, unrestrained cats.
The administration of the sympathomimetic agents (+)‐amphetamine, methamphetamine, tyramine, and ephedrine resulted in a highly significant decrease in the duration of epileptiform afterdischarge (EADs).
The α‐adrenoceptor blocking drugs phenoxybenzamine, phentolamine and tolazoline did not significantly alter the duration of EADs but prevented the decrease in duration of EADs produced by the sympathomimetic drugs.
The effect of atropine and arecoline on the duration of EADs, previously described, were not modified by the α‐adrenoceptor blocking drugs, but atropine prevented and reversed the inhibitory action of amphetamine.
It is suggested that (1) in the chronically neuronally isolated cortical slab there is normally no spontaneous adrenergic activity, (2) a cortical, cholinergic inhibitory mechanism, previously described, is modulated by ascending adrenergic influences, (3) adrenergic cholinergic linkages might be arranged in the cortex in an alternating network, as proposed by Feldberg.
Effect of reserpine on the activity of adrenal enzymes involved in the synthesis of adrenaline
Authors: BHAGAT B. , BURKE W. J. , DAVIS J. W. 
Published: July 2012

Summary
After administration of reserpine to rats, the tyrosine hydroxylase (TH) and phenylethanolamine‐N‐methyl transferase (PNMT) activity in their adrenal glands was found to be increased under in vitro conditions.
The increase in TH activity occurred at 12–18 h after reserpine whereas the PNMT activity increased at 30 hours. Unlike the TH, the increase in PNMT activity did not appear to be neuronally mediated since ganglion blockade by chlorisondamine failed to antagonize the reserpine‐induced increase in PNMT activity. The increase in PNMT activity may be a response to increased utilization of catecholamines.
Hypophysectomy resulted in a diminution of the activities of both enzymes; the activity of TH, but not of PNMT, could be partially restored by reserpine. ACTH restored the activities of both enzymes almost to normal.
The differential effect of reserpine suggests that the activities of these two enzymes are controlled by different mechanisms.
Factors influencing the aggressiveness elicited by marihuana in food‐deprived rats
Authors: CARLINI E. A. , HAMAOUI A. , MÄRTZ REGINA M. W. 
Published: July 2012

Summary
Aggressive behaviour was elicited in rats that had been deprived of food for 20 h daily (starved), by chronic administration of Cannabis sativa extract or (—)‐Δ9‐trans‐tetrahydrocannabinol.
The influence of intraperitoneal (i.p.) or oral glucose administration, cold environment, acidosis, and corn, and protein‐free diets on this aggressiveness was studied.
Intraperitoneal injections of glucose (100–1,600 mg/kg) did not alter the aggressiveness induced by marihuana in starved rats; glucose given orally, however, blocked this behaviour.
Low temperature (14° C) strongly potentiated the aggressive behaviour induced by marihuana in the starved rats.
Lactic acid in doses capable of potentiating thiopental anaesthesia, failed to alter the marihuana‐aggressiveness of starved rats or to facilitate this effect of marihuana in rats fed ad libitum. The same negative results were obtained with ammonium chloride.
In rats fed ad libitum with protein‐free or corn diets, marihuana administered chronically did not elicit aggressive behaviour. However, aggressiveness appeared when rats were fed for only 2 h daily on those diets.
The results suggest that the stress of hunger (and not hypoglycaemia, acidosis or lack of specific nutrients due to starvation) is the factor that facilitates the development of aggressive behaviour by chronic administration of marihuana.
Prostaglandins, oxygen tension and smooth muscle tone
Authors: ECKENFELS A. , VANE J. R. 
Published: July 2012

Summary
By using indomethacin to inhibit their intramural synthesis, we have investigated the contribution of prostaglandins to the maintenance of (a) the intrinsic tone of isolated smooth muscle preparations and (b) contractions produced by drugs or high oxygen concentration.
When treated with indomethacin, the rat stomach strip and chick rectum preparation slowly relaxed, whether they were bathed in Krebs solution or blood. Although their sensitivity to added prostaglandin was somewhat enhanced, they became insensitive to changes in oxygen or glucose concentration. However, another smooth muscle preparation, the rat colon, was neither relaxed by indomethacin nor contracted by high oxygen concentration.
These results support the hypothesis that intramural generation of prostaglandin maintains the tone of some smooth muscle preparations.
Contractions of the guinea‐pig isolated colon were induced by histamine. These contractions were normally well maintained but in Krebs solution lacking either oxygen or glucose, only the initial spike contraction remained. In the presence of indomethacin the histamine contraction was also poorly sustained, but maintenance was restored by a low concentration of prostaglandin E2.
Thus, the effects on smooth muscle of oxygen or glucose lack may also be mediated by reduction in the synthesis or effects of an intramural prostaglandin. Extension of this hypothesis to intestinal and vascular smooth muscle in vivo is discussed.
A method for measuring human behavioural and physiological responses at different stress levels in a driving simulator
Authors: ASHTON HEATHER , SAVAGE R. D. , THOMPSON J. W. , WATSON D. W. 
Published: July 2012

Summary
A method is described by which a car simulator can be used to measure, simultaneously, motor‐perceptual performance and physiological responses of human subjects under different levels of task difficulty or stress.
Motor‐perceptual performance was measured in terms of reaction times taken by subjects to carry out steering, braking and operation of traffic indicators in the simulator. Subjects were instructed to carry out the different driving manoeuvres by means of a command panel containing five coloured lights. Three levels of task difficulty or stress were devised. In level 1 only the light signals were used. In level 2 the driving simulator film was shown and all of the light signals reinforced the movements of the car in the film. Level 3 was similar to level 2, with the exception that whilst some of the light signals reinforced the movements of the car, others deliberately conflicted with it.
Physiological responses measured were heart rate, blood pressure, respiration and calf blood flow. Personality was also measured by means of the Cattell 16 personality factor questionnaire.
Analysis of variance of the performance of 15 subjects showed significant variation between the three task levels (P = <0·001 for steering reaction times; P = <0·01 for brake and indicator reaction times). In all cases the reaction times were longest for level 3, indicating that this was the most difficult task. The number of anticipated responses to steering, braking and traffic indicator signals was highest in level 2, while the number of corrections to steering and braking responses was lowest in level 2. None of these differences was statistically significant.
Of the physiological variables, the heart rate showed a progressive increase from task levels 1 to 3 but only those between levels 1 and 3 were statistically significant (P<0·05).
The results are discussed in relation to the validity of the method. It is concluded that by means of this method it is possible to produce controlled and reproducible degrees of stress and under conditions which are also suitable for the investigation of pharmacological agents upon it.
The effects of some phosphodiesterase inhibitors on the conductance of the perfused vascular beds of the chloralosed cat
Authors: HAMILTON T. C. 
Published: July 2012

Summary
The vasoactivity of a number of phosphodiesterase inhibitors in the autoperfused splanchnic region and hindquarters of the cat have been investigated.
Theophylline, dipyridamole and 4‐(3,4‐dimethoxybenzyl)‐2‐imidazolidinone (Ro 7–2956) and its analogues were more potent vasodilators in the splanchnic region than in the hindquarters, whereas papaverine was a potent vasodilator in both these vascular beds.
The vasodilator response to the phosphodiesterase inhibitors in the splanchnic region and hindquarters was not susceptible to β‐adrenoceptor blockade.
Infusion of dibutyryl cyclic AMP into the superior mesenteric artery increased vascular conductance of the splanchnic region. This effect was enhanced by Ro 20–1724 in doses below those in which this compound affected conductance.
These results are consistent with the hypothesis that accumulation of cyclic AMP in vascular smooth muscle mediates the vasodilator response to phosphodiesterase inhibitors.
Effects of an isolated toxin from Australian Tiger snake (Notechis scutatus scutatus) venom at the mammalian neuromuscular junction
Authors: HARRIS J. B. , KARLSSON E. , THESLEFF S. 
Published: July 2012

Summary
The acute effects of a purified toxin from Australian Tiger snake (Notechis scutatus scutatus) venom have been investigated at the mammalian neuromuscular junction.
The toxin was injected into the tail vein of mice. Death was due to respiratory paralysis.
The resting membrane potential, and action potential of muscle fibres in muscles from in vivo intoxicated animals were normal.
The frequency of miniature end plate potentials (m.e.p.p.s) from intoxicated nerve‐muscle preparations was reduced, although m.e.p.p. amplitude was unaltered.
Nerve stimulation resulted in end plate potentials (e.p.p.s) of quantal amplitude; only rarely was the e.p.p. large enough to give rise to an action potential.
High (20 mm) K+ did not increase m.e.p.p. frequency in intoxicated preparations.
The toxin was largely ineffective in vitro.
The similarities and differences between this toxin, β‐bungarotoxin and botulinum toxin are discussed.
N,O‐di andN,N,O‐tri [3H] acetyl α‐bungarotoxins as specific labelling agents of cholinergic receptors
Authors: CHANG C. C. , CHEN T. F. , CHUANG SING‐TAI 
Published: July 2012

Summaryα‐Bungarotoxin isolated from the venom ofBungarus multicinctuswas acetylated with [3H] acetic anhydride andN‐[3H] acetyl imidazole. Tri‐N‐acetyl and hexa‐N‐acetyl derivatives were obtained from the former, andN,O‐di,N,N,O‐tri andN,N,N,O‐tetraacetyl derivatives from the latter reaction, respectively.There were parallel decreases in both neuromuscular blocking action in the phrenic nerve—diaphragm preparation of rats and depression of acetylcholine response of the rectus abdominis muscle of frogs with increased acetylation. Also, a parallel but greater decrease of toxicity in mice was found.N,O‐Di andN,N,O‐triacetyl toxins were localized mostly in the motor endplate region of the rat diaphragm, whereas a slight nonspecific binding along the whole muscle fibre in addition to the peak in the endplate region was observed withN,N,N,O‐tetraacetyl and tri‐N‐acetyl toxins. In contrast, there was a marked nonspecific binding with hexa‐N‐acetyl toxin and no peak was observed at the endplate zone.The specific binding was saturable and irreversible. The number of toxin‐receptive sites in one endplate was 1·9–2·2 × 107for all of the labelled toxins irrespective of their potency.(+)‐Tubocurarine protected effectively against the binding as well as the irreversible neuromuscular blocking effect of the toxins.Denervation of the rat diaphragm caused an increase of toxin‐receptive sites beginning from the endplate zone at 1–2 days and then along the whole muscle fibre, reaching the maximum at about 18 days. The total receptive sites increased by about 30‐fold.The significance of the findings is discussed and it is concluded thatN,O‐di andN,N,O‐tri‐[3H] acetyl α‐bungarotoxins are specific and irreversible labelling agents for the cholinergic receptors of skeletal muscle.
The structure of hydroxyethyl starch
Authors: BANKS W. , GREENWOOD C. T. , MUIR D. D. 
Published: July 2012

Summary
It is suggested that the structure currently used to describe hydroxyethyl starch (a blood plasma volume expander) is a gross oversimplification.
A model having a much more complex substitution‐pattern is proposed, and an accurate, rapid test has been devised for distinguishing between the two models.
This test shows that the simple model has no basis in reality, and that the more complex substitution pattern is correct.
Studies involving the enzymic hydrolysis of hydroxyethyl starch are shown to provide qualitative support for the new model, and the significance of the findings is discussed.
Further observations on mesenteric vasoconstriction, survival and the clotting defect after endotoxin administration
Authors: COHEN M. M. , GREENWAY C. V. , INNES I. R. , LISTER G. E. , MURTHY V. S. , SCOTT G. D. 
Published: July 2012

Summary
The initial response after endotoxin administration (3 mg/kg) in cats involved pulmonary vasoconstriction. This was not seen when endotoxin was given by slow infusion and it could be prevented after a bolus injection of endotoxin by pretreatment of the cats with aspirin (10 mg/kg). Intense mesenteric vasoconstriction occurred in all the cats.
The mesenteric vasoconstriction was a specific response of the mesenteric blood vessels. At the time the mesenteric bed constricted, the renal bed dilated, the hepatic arterial bed remained unchanged and the smooth muscle of the intestinal wall relaxed.
Arterial blood from cats with a fully developed mesenteric vasoconstriction after endotoxin administration was perfused through a normal intestine. No immediate vasoconstriction developed but the perfused intestine constricted slowly over 60 minutes. This suggests that mesenteric constriction was not due to circulating vasoconstrictor factors or the intestinal innervation, but involved a slow local mechanism within the intestine. It could not be prevented or reversed by a variety of pharmacological agents.
These observations suggest that endotoxin caused a unique type of mesenteric vasoconstriction in cats by a local mechanism which took up to 60 min to develop, was sufficiently potent to reduce mesenteric flow to <30% control, and was maintained until death of the cats. Blood from these animals did not clot when placed in a glass tube.
The mesenteric constriction and the clotting defect could be prevented by repeated administration of aminophylline and dextran solution before and after a bolus intravenous injection of endotoxin. Arterial pressure and mesenteric flow were maintained for at least 10 h in these experiments. Inadequate treatment intensified rather than reduced the intestinal mucosal damage.
Cats were treated with aspirin, endotoxin and the optimal regimen for prevention of the mesenteric constriction and allowed to recover from the anaesthetic agent. In this series, 63% survived indefinitely compared to 25% after aspirin and endotoxin treatment and 0% after endotoxin alone.
The possible mechanisms of action of aspirin and aminophylline‐dextran solution are discussed. Our failure to obtain 100% survival is probably due to pulmonary damage which develops 10–24 h after endotoxin administration. This delayed pulmonary action of endotoxin is not prevented by aspirin treatment and it seems unlikely that aspirin will be of any value in the treatment of the pulmonary lesion in man.