bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of effect of morphine‐like analgesics on transmurally stimulated guinea‐pig ileum
Authors: FENNESSY M. R. , HEIMANS R. L. H. , RAND M. J. 
Published: July 2012

. Morphine‐like analgesic drugs caused depression of twitches of the isolated guinea‐pig ileum in response to transmural electrical stimulation. The drugs tested were the narcotic analgesics codeine, diamorphine, fentanyl, morphine, morphine‐N‐oxide, normorphine, oxymorphone, pethidine, phenazocine and phenoperidine and the analgesic narcotic antagonists nalorphine and pentazocine.
. With the first application of one of these drugs the extent of depression of twitches was proportional to concentration. Except in the case of pethidine, there was no further depression when additional drug was added to the organ bath. With the second application of a drug after washing out the first dose, the depressant effect was less; that is, tolerance developed. With pethidine, the depression of twitches was proportional to concentration and tolerance could not be observed.
. When tolerance had been produced by cumulative addition of these drugs, a concentration was reached at which further addition resulted in increased activity of the ileum.
. With codeine, morphine and normorphine, the twitches were increased in height and regular.
. With diamorphine, fentanyl, oxymorphone, pentazocine, phenazocine and phenoperidine there were increased but irregular responses to transmural stimulation.
. Having reached the concentration at which these effects were observed, washout of the drug resulted in reduction of activity; the twitches became smaller or the irregular responses ceased.
. Readministration of a drug after activity of the ileum had been depressed by withdrawal of that drug resulted in restoration of activity, the ileum being dependent on the presence of the drug for its activity.
. Codeine and nalorphine did not produce as great an increase in activity on readministration to a dependent ileum as did morphine: they seem to act as partial agonists in producing this effect.
. In similar experiments with the isolated urinary bladder of the rat and guinea‐pig, morphine was less active in depressing responses to stimulation than it was on the ileum, and tolerance to the drug and dependence on it did not occur.
. These observations have been discussed in relation to analgesic activity, tolerance and dependence in man.
Sedative properties of simple analgesics
Authors: HUNT J. N. , LALLEMAND R. C. 
Published: July 2012

. An attempt has been made to assess under double blind conditions the sedative action of phenacetin, paracetamol, and aspirin by testing their ability to prolong sleep in the face of a rapidly filling bladder.
. The volume in the bladder on awakening was independent of the rate of urine formation.
. Although phenacetin prolonged sleep there was no corresponding increase in urine volume on awakening. Apparently phenacetin sensitized the bladder to the distending volume and reduced the rate of urine formation. It was unnecessary to postulate sedative action to explain the results.
. Paracetamol had no effect on the mean sleep interval or mean urine volume although the drug was not totally inactive since it increased the variance of the results for sleep interval and urine volume.
. Aspirin prolonged sleep interval, but this effect would be explained if it were an antidiuretic because there was no increase in urine volume on awakening.
. Apparently no sedative or hypnotic has been shown to increase the urine volume on awakening under similar conditions.
The effect of aflatoxin on blood clotting in the rat
Authors: BABABUNMI E. A. , BASSIR O. 
Published: July 2012

. The action of aflatoxin on blood clotting of rats was investigated. Aflatoxin B1 prolonged the blood clotting time of rats.
. Aflatoxin B1 was effective as an anticoagulant in much smaller doses than 4‐hydroxycoumarin.
Role of the sympathetic nervous system in daunomycin‐induced arrhythmia in the monkey
Authors: BURKA B. , HERMAN E. , VICK J. 
Published: July 2012

Infusion of daunomycin 50 mg/kg in the monkey consistently induced ventricular arrhythmias which were not influenced by bilateral vagotomy.
A central sympathetic component to the arrhythmias was suggested because spinal transection, ganglionic blockade or bilateral stellate ganglion‐ectomy prevented any alterations in the e.c.g.
Bilateral adrenalectomy or splanchnic nerve section protected three of six animals. This source of catecholamines may not be necessary in every case to initiate the arrhythmia.
Guanethidine was a relatively ineffective antiarrhythmic agent. Timing appears to be important with this agent.
Pargyline, by monoamine oxidase inhibition or other mechanisms, significantly lowered the arrhythmic dose of daunomycin. Reserpine pre‐treatment, on the other hand, prevented any e.c.g. alterations following daunomycin.
Phenoxybenzamine exerted significant protection which may be related to its cardiodepressant properties.
Alterations in e.c.g. were seen in all (+)‐propranolol pretreated animals, although the arrhythmic period was modified in two of three experiments. Racemic (±)‐propranolol, which exerts direct myocardium depression as well as β‐adrenoceptor blockade, was completely protective in four of five experiments. The results of the present experiments indicate that the sympathetic nervous system is intimately involved in the daunomycin arrhythmia.
The effects of dimethothiazine on muscle spindle activity in the decerebrate cat
Authors: MAXWELL D. R. , RHODES K. F. 
Published: July 2012

The effects of dimethothiazine have been studied on the response of afferent fibres from primary and secondary endings of muscle spindles in the soleus muscle of the decerebrate cat during stretching of the muscle under controlled conditions.
Dimethothiazine in doses of 1 to 4 mg/kg intravenously reduced the discharge frequency of primary and secondary endings. Higher doses of dimethothiazine had little further significant effect on the discharge frequency.
The discharge frequency recorded from de‐efferented muscle spindles in soleus of the decerebrate cat were similar to the discharge frequencies obtained in preparations with intact ventral roots which had received a high dose of dimethothiazine.
Dimethothiazine had little significant effect on the discharge frequency of afferent fibres from muscle spindles in the soleus muscle of decerebrate preparations where the ventral roots were cut.
These effects of dimethothiazine on muscle spindle activity were not related to any changes in blood pressure of the decerebrate cat.
Dimethothiazine appears to reduce the effects of both the dynamic and static fusimotor fibres on the spindle.
The doses of dimethothiazine which effect spindle discharge frequency are similar to those required to reduce decerebrate rigidity.
Adrenoceptors in the cat choledochoduodenal junction studiedin situ
Authors: LIEDBERG G. , PERSSON C. G. A. 
Published: July 2012

The effects of adrenaline, noradrenaline, isoprenaline and terbutaline (PINN), 1‐(3,5‐dihydroxyphenyl)‐2(t‐butylamino)‐ethanol, on the sphincter of Oddi were studied in anaesthetized cats. Both adrenaline and noradrenaline (1–4 μg/kg) increased resistance to flow through the sphincter. This effect was blocked by dibenamine (0·5–2·5 mg/kg) and by phenoxybenzamine (0·5–1·0 mg/kg).Isoprenaline (0·5–5·0 μg/kg) as well as terbutaline (0·5–10·0 μg/kg) inhibited the spontaneous sphincter activity and decreased flow resistance. In these doses, isoprenaline provoked marked tachycardia and relaxation of the duodenum, whereas the cardial and intestinal effects of terbutaline were minimal. The effects were blocked by propranolol (0·5–1·0 mg/kg).The results confirm earlier observations of the presence of α‐adrenoceptors active in contraction of the sphincter musculature and of β‐adrenoceptors active in its relaxation. It is suggested that the β‐adrenoceptors belong to the β2type according to Lands' classification.
Studies on the receptors involved in the action of the various agents in the phenylbenzoquinone analgesic assay in mice
Authors: SMITSs S. E. , TAKEMORI A. E. 
Published: July 2012

Tolerance to the activity of several narcotic analgesics (morphine, levorphanol, and methadone) and several narcotic‐antagonist analgesics (pentazocine, cyclazocine, and nalorphine) was studied in the mouse phenylbenzoquinone stretching test. Virtually complete tolerance was induced by chronic treatment with each of the narcotic agents, while no apparent tolerance was induced by the narcotic antagonists.
In morphine‐tolerant mice there was a high degree of cross‐tolerance to the effects of not only the other narcotic drugs but also to those of the narcotic antagonists, acetylsalicylic acid, and physostigmine.
The effects of morphine and pentazocine were antagonized by naloxone but not by atropine, while the effects of physostigmine were antagonized by atropine but not by naloxone. Neither atropine nor naloxone antagonized the effect of acetylsalicylic acid.
The results of the tolerance study suggest that there is a fundamental difference in the consequences of receptor interaction for the narcotic and the narcotic‐antagonist analgesics. Morphine‐tolerant mice exhibit cross‐tolerance non‐specifically. The selectivity of naloxone and atropine differentiates the narcotic and narcotic‐analgesics from the other two agents used in this analgesic test.
Comparative chronotropic activity of β‐adrenoceptive antagonists
Authors: BARRETT A. M. , CARTER J. 
Published: July 2012

. Chronotropic dose‐response curves (non‐cumulative) for β‐adrenoceptive antagonists were constructed from results in rats anaesthetized with pentobarbitone and depleted of catecholamines by pre‐treatment with syrosingopine.. Depletion of catecholamines lowered resting heart rate and reduced the threshold to the chronotropic action of isoprenaline by about 50%. Eight β‐adrenoceptive antagonists produced a dose‐dependent chronotropic response but the maximum response was in all cases smaller than that obtained with isoprenaline. The order of activity was dichloroisoprenaline>LB 46>practolol>INPEA>oxprenolol>pronethalol>alprenolol>I.C.I. 45,763 (Kö 592). Propranolol and sotalol were without significant activity. The duration of the chronotropic response to the antagonists was more prolonged than that to isoprenaline. Propranolol caused a parallel shift to the right of the dose‐response curves for the agonist effects of the antagonists.. Estimation of β‐adrenoceptor blocking activity in anaesthetized cats gave an order of activity dissimilar to that found for maximum agonist responses: LB 46 > Oxprenolol > alprenolol > propranolol > I.C.I. 45,763 > practolol > dichloroisoprenaline > sotalol > INPEA > pronethalol.. Consideration of chemical structure and physico‐chemical properties did not explain the differences between the agonist activities of the adrenoceptive antagonists.
The effect of ethyl alcohol and chlorpromazine on the response of the hand blood vessels to cold
Authors: DOWNEY J. A. , FREWIN D. B. 
Published: July 2012

. The response of hand blood flow to a measured cold stimulus was determined using venous occlusion plethysmography in normal subjects, before and after orally administered alcohol, and in patients on chlorpromazine therapy.
. The average resting hand blood flow of the patients taking chlorpromazine, as well as the constriction of these blood vessels to cold, was the same as in the normal subjects.
. Oral alcohol caused a rise in resting hand blood flow in the normal subjects and also modified the response of the hand blood vessels to cooling.
. A patient with a completely denervated hand was also studied. Oral alcohol did not increase the blood flow through the part, but it modified the hand vascular response to cold.
. These results suggest a diminished reactivity of the hand blood vessels to cold in the presence of alcohol.
Effects of chronic metaraminol treatment on the sympathetic activity of intact and adrenal demedullated rats kept in warm or cold environments
Authors: JOHNSON G. E. , PUGSLEY T. A. 
Published: July 2012

. Rats were placed at 27° C or 4° C and given metaraminol ((10 mg/kg)/day) in their drinking water for 8 weeks. One experiment was run using adrenal demedullated rats. These animals were treated with metaraminol, as mentioned above, and kept at 4° C for 4 weeks.
. Body temperature and metabolic rate were determined at selected intervals. Urine was collected on day 7 of each week and analysed for adrenaline, noradrenaline, metanephrine, normetanephrine and 3‐methoxy‐4‐hydroxyphenyl‐glycol (MHPG). At the end of each study the rats were killed and the tissues removed and analysed for metaraminol, adrenaline and noradrenaline.
. All animals survived the metaraminol treatment and no change in metabolic rate or body temperature was seen. Metaraminol depressed the growth rate of the rats.
. Metaraminol caused a fall in tissue noradrenaline concentrations, with only negligible quantities being found in brain, heart, lung, liver, kidney and spleen. Only the adrenals contained significant quantities of catecholamines. All tissues contained large amounts of metaraminol.
. Despite the almost complete depletion of noradrenaline from sympathetic nerves, metaraminol did not depress the excretion of noradrenaline, normetanephrine and MHPG, in fact excretion of the latter two substances was higher in the treated animals. The failure of the drug to impair the normal cold‐induced increase in noradrenaline secretion explains the survival of the rats at 4° C.
. Adrenal demedullation did not prevent the metaraminol‐treated rats from excreting large quantities of noradrenaline, normetanephrine and MHPG in the cold. It is apparent, therefore, that in the intact rats the noradrenaline emanated from the practically depleted nerves. The increase in MHPG excretion, seen during metaraminol treatment, suggests an increased rate of noradrenaline turnover.
. In conclusion, although metaraminol uptake is accompanied by a fall in tissue noradrenaline concentrations, the presence of metaraminol does not depress noradrenaline release. These results do not support the concept that metaraminol can replace noradrenaline and function as a false transmitter.
The effects of “autonomic drugs” on villous movement in the small intestine of the pigeon
Authors: HOOPER PATRICIA A. , SCHNEIDER R. 
Published: July 2012

. The responses of pigeon duodenal villi to intravenous injection or local application of “autonomic drugs” were studied and compared with those reported in dogs by other workers.
. Choline esters, anticholinesterases, noradrenaline, adrenaline and nicotine all stimulated villous movement in the pigeon. Similar responses to these drugs have been reported in the dog. The effects of these drugs on villous activity could be inhibited by pretreatment of the bird with suitable antagonists, although hexamethonium was ineffective in preventing the effects of nicotine. Some of the antagonists also stimulated the villi.
. Isoprenaline caused inhibition of villous movements, which could be prevented by pretreatment of the bird with propranolol. It appears that in pigeons the villi have both α‐adrenoceptors, stimulation of which increases villous activity, and β‐adrenoceptors, stimulation of which depresses villous movements.
The action of pharmacologically active substances on the flow and composition of cat hind limb lymph
Authors: LEWIS G. P. , WINSEY N. J. P. 
Published: July 2012

. Lymph flow, blood flow and lymph protein concentrations have been measured in cat hind limb.
. When naturally occurring pharmacologically active compounds were infused close arterially to the hind limb it was found that histamine, bradykinin and acetylcholine were the most potent in increasing lymph flow.
. Dilatation of blood vessels per se is not sufficient to cause an increase in lymph flow since potent vasodilator agents such as isoprenaline and prostaglandins were not very active in increasing lymph flow.
. The effect on blood flow was rapid in onset and in return to basal flow, whereas the effect on lymph flow was delayed and prolonged. The duration of the effect on lymph flow was considerably greater with histamine and bradykinin than with acetylcholine.
. An increase in the protein concentration in the interstitial fluid is not a pre‐requisite of an increase in lymph flow because (a) in some experiments an increase in lymph flow was not accompanied by an increase in lymph protein concentration after infusion of vasoactive substance and (b) the glucofuranoside, Glyvenol, was found to inhibit the increase in protein concentration but not the increase in lymph flow caused by infusion of histamine or bradykinin.
. In contrast the specific antihistamine, mepyramine, abolished the effect of histamine on lymph flow and lymph protein concentration and considerably reduced the effect on blood flow.
. An increase in venous pressure alone caused a small increase of lymph flow in about 50% of experiments, but when the venous pressure was increased at a time when vascular permeability was high, there was an increase in lymph flow in all experiments.
. When the venous pressure was low only histamine caused a significant increase in the lymph protein concentration, whereas bradykinin sometimes caused a small increase and acetylcholine mostly caused a decrease in the concentration of lymph protein.
. When the venous pressure was high, bradykinin and histamine and occasionally acetylcholine caused an increase in protein concentration in the lymph.
. Infusions of histamine, bradykinin or prostaglandin E1 did not increase the leakage of intracellular enzymes into the lymph.
Distribution and metabolism of l‐3‐O‐methyldopa in rats
Authors: BARTHOLINI G. , KURUMA I. , PLETSCHER A. 
Published: July 2012

. After intraperitoneal administration of l‐2−14C‐3‐O‐methyldopa (14C‐O‐methyldopa) to rats, the amino‐acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. 14C‐O‐methyldopa showed a biological half‐life of about 12–13 h in blood, brain and heart.
. The concentration curve of 14C‐O‐methyldopa in brain (after increasing doses of the amino‐acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h.
. The concentrations of 14C‐O‐methyldopa metabolites (mainly homovanillic acid and 4‐hydroxy‐3‐methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue.
. Twenty‐four hours after administration of 14C‐O‐methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main 14C‐homovanillic acid and 14C‐4‐hydroxy‐3‐methoxyphenyllactic acid) and of 5% of unchanged 14C‐O‐methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end‐products.
. It is concluded that 14C‐O‐methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino‐acid undergoes a slow metabolism. The different shape of the concentration curves for 14C‐O‐methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino‐acid.
Turnover rate of brain 5‐hydroxytryptamine increased by D‐amphetamine
Authors: REID W. D. , DERR JULIA 
Published: July 2012

. Administration of two doses of amphetamine HCl (5 mg/kg intraperitoneally) 45 min apart raised body temperature of rats by an average of 3·4° C and increased the turnover rate of brain 5‐hydroxytryptamine (5‐HT) by almost one‐half.
. Both effects were blocked by exposure to 4° C or by pretreatment with the β‐blocker Kö 592 (1‐(2‐methylphenoxy)‐3‐isopropylamino‐2‐propanol), but not by the administration of the ganglionic blocker chlorisondamine combined with atropine.
. Since it has previously been shown that hyperthermia per se increases the turnover rate of brain 5‐HT, and that amphetamine does not directly affect the uptake and release of 5‐HT in brain slices, it is concluded that the amphetamine‐induced increase in 5‐HT turnover may be secondary to the rise in temperature produced by the drug.
Positive correlation between initial pupil diameter and amplitude of miotic response to pilocarpine in rabbits and to carbachol in man
Authors: Burns J. , Horlington M. , Robson D. 
Published: July 2012

A linear correlation between amplitude of miotic response and initial pupil diameter has been demonstrated in rabbits using various concentrations of pilocarpine HC1. The same correlation was found when published results in humans using carbachol were examined andit is likely that the correlation also applies to pilocarpine in humans. No such correlation was observed with physostigmine.
The sensitivity of the brain to barbiturate during chronic administration and withdrawal of barbitone sodium in the rat
Authors: STEVENSON I. H. , TURNBULL M. J. 
Published: July 2012

Summary
The sensitivity of the central nervous system to barbiturate was determined in rats during the chronic administration of barbitone sodium and after its withdrawal.
The brain barbiturate concentration determined on awakening from a hypnotic dose administered intraperitoneally was found to increase throughout the period of barbitone administration.
A similar gradual development of central nervous system tolerance was indicated by measuring the duration of anaesthesia following an intraventricular injection of pentobarbitone.
The change in sensitivity of the brain which occurred during the period of barbitone administration was not demonstrable from the measurement of sleeping time following intraperitoneal injection of barbitone or pentobarbitone.
After withdrawal, the sensitivity of the brain to barbiturate gradually returned to normal.
It was concluded that the hypersensitivity to pentobarbitone, but not to barbitone, which develops after withdrawal of barbitone sodium is due to a decreased drug‐metabolizing capacity.
An improved method for studying the peristaltic reflex in the isolated colon
Authors: FRIGO G. M. , LECCHINI S. 
Published: July 2012

Summary
A method is described for studying the peristaltic reflex in the guinea‐pig or cat isolated colon, using a graded localized intraluminal stimulus consisting of a solid bolus.
The method gives an easy evaluation of propulsive activity and makes it possible to record simultaneously the segmental activity of the circular muscle in relation to the site of stimulation and the contractions and relaxations of the longitudinal muscle coat.
The velocity of propulsion, which is a reliable measure of propulsive activity, is dependent on the degree of distension and is easily affected by physical agents and nervous stimulation. A solid bolus is propelled only when there is simultaneous ascending contraction and descending inhibition of the circular musculature.
Since the peristaltic reflex could not be elicited from areas from which the mucosal and submucosal layers had been removed, these layers are essential for the triggering of the peristaltic reflex and for the propulsion of solid contents in the colon.