bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane
Authors: SUMMERS R. J.
Published: July 2012

. In cats, the effects of intraperitoneal injections of four monoamine oxidase (MAO) inhibitors, tranylcypromine, pheniprazine, pargyline, and nialamide, were examined on rectal temperature and on the hypothermia during anaesthesia produced by a 2 hr period of halothane inhalation.

. A 2 hr period of halothane inhalation produced a steady fall in temperature amounting to between 2° and 3·5° C. After discontinuation of halothane inhalation, temperature quickly returned to the pre‐anaesthetic level but no pyrexia developed. A peculiar stiffness of the leg muscles occurred in several experiments either at the beginning of the inhalation or after its discontinuation.

. An injection of tranylcypromine (5 mg/kg) caused a rise in rectal temperature and prevented the hypothermia of halothane anaesthesia. This effect lasted for at least 4 hr; 20 hr after the injection, halothane again caused hypothermia.

. An injection of pheniprazine (10 mg/kg) usually caused a small rise in temperature which was not sustained. Pheniprazine not only prevented the hypothermia of halothane anaesthesia during the subsequent 20 hr, but during the first few hours after the injection halothane inhalation actually produced a steep rise in temperature.

. An injection of pargyline (50 mg/kg) had no effect on temperature but the hypothermia due to halothane inhalation was prevented 1 hr after the injection and attenuated after 20 hr. Injection of 200 mg/kg caused a steady rise in temperature which was accelerated when halothane was administered 1 hr later.

. An injection of nialamide (10, 25 or 50 mg/kg) had no immediate effect on temperature, but pyrexia developed overnight after the two larger doses. The effect on the hypothermia due to halothane inhalation was greater 20 hr after the injection than it was after 1 to 2 hr. Twenty hours after injection of the two larger doses, halothane no longer produced hypothermia but caused a lethal rise in temperature either during or after its inhalation.

. In rabbits, the effect on temperature of halothane inhalation varied. Either temperature rose slightly or it fell, but not as much as in cats. In one rabbit in which the inhalation had produced a transient rise, pyrexia developed 40 min after discontinuation of halothane.
Some properties of the denervated anterior gracilis muscle of the rat
Authors: TURKANIS S. A.
Published: July 2012

. Microdrops of acetylcholine (ACh) were topically applied to denervated, mammalian skeletal muscle in vivo, and ACh‐evoked depolarization and contracture were recorded simultaneously.

. Contracture tension was directly proportional to the degree of ACh‐elicited depolarization.

. Atropine and (+)‐tubocurarine increased the amount of ACh required to produce a given amount of depolarization, but these anticholinergic agents did not alter the relationship between the degree of ACh‐evoked depolarization and contracture tension.

. Topically applied catecholamines did not produce either depolarization or contracture, despite the fact that parenterally administered catecholamines elicited both responses.
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 and

it is likely that the correlation also applies to pilocarpine in humans. No such correlation was observed with physostigmine.
pP2 of eserine and neostigmine on acetylcholine responses of isolated ileum
Authors: Edge N. D.
Published: July 2012

pPsvalues of 7·9 and 8·0 for eserine and neostigmine show that these compounds are respectively about 200 and 300 times more potent in potentiating acetylcholine (ACh) responses on isolated cavy ileum than was previously found on frog rectus muscle. The increased tone and spontaneity usually produced by eserine and neostigmine were not prevented by morphine (10 to 100 μg/ml), which itself potentiated both ACh and histamine responses.
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

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

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.
Phase separation in solutions of noradrenaline and adenosine triphosphate: influence of bivalent cations and drugs
Authors: BERNEIS K. H. , PLETSCHER A. , DA PRADA M.
Published: July 2012

From aqueous solutions of biogenic amines, such as noradrenaline plus adenosine triphosphate (ATP), a second liquid phase spontaneously separates in the presence of small amounts of bivalent cations such as calcium. This separation is reversible and temperature‐dependent; the concentration of amine and ATP in the bottom phase is several times higher than in the supernatant.

Analytical ultracentrifugation provides evidence that the second phase consists of high molecular weight aggregates of the amine and ATP.

The separated second phase of the noradrenaline‐ATP system dissolves isothermally on addition of tyramine and amphetamine which in vivo are known to liberate biogenic monoamines and which have a low tendency to aggregate with ATP. The apparent molecular weights of noradrenaline‐ATP aggregates are decreased by tyramine and amphetamine. Dopamine does not diminish the second phase and it can also form aggregates of high molecular weight with ATP.

Bivalent cations in high concentrations diminish or abolish the separation of a second phase.

Small amounts of reserpine affect phase separation.

It is concluded that the physico‐chemical properties of aggregates of biogenic amines with ATP may be of importance for understanding the storage and release of the amines in vivo.
Interactions of inhibitors of noradrenaline uptake and angiotensin on the sympathetic nerves of the isolated rabbit heart
Authors: SCHÜMANN H. J. , STARKE K. , WERNER U.
Published: July 2012

The interaction of angiotensin and several inhibitors of the uptake of noradrenaline across the neuronal membrane (cocaine, desipramine, protriptyline, and pronethalol) on the output of noradrenaline produced by sympathetic nerve stimulation has been studied in the isolated perfused rabbit heart.

Most of these drugs increased noradrenaline outflow—angiotensin, for example, by 175%. Cocaine (10−4m) did not change the amine overflow, probably because this very high concentration inhibited not only the re‐uptake but also the liberation of noradrenaline.

Desipramine, protriptyline, and pronethalol, although infused in concentrations which enhanced the noradrenaline output, were not able to impair the angiotensin‐induced increase of transmitter overflow. In the presence of cocaine (10−4m) the increase elicited by angiotensin was slightly reduced, though lower concentrations of cocaine, as previously described, do not interfere with the effect of angiotensin.

In contrast to the interaction between uptake inhibitors and angiotensin, the augmented output of noradrenaline caused by an uptake inhibitor could not be increased further by infusion of a second uptake inhibitor.

It is concluded that the increase of the outflow of noradrenaline during sympathetic nerve stimulation by small doses of angiotensin is not caused by an inhibition of re‐uptake. On the contrary, the transmitter liberation seems to be facilitated. This is a novel principle of drug action on the sympathetic nerve terminals.
The distribution of antibacterial agents between plasma and lymph in the dog
Authors: ACRED P. , BROWN D. M. , CLARK B. F. , MIZEN LINDA
Published: July 2012

Plasma, peripheral and thoracic lymph concentrations of penicillin V, phenethicillin, carbenicillin, ampicillin, cloxacillin, penicillin G, chloramphenicol and sulphadiazine were determined at various time intervals up to 6 h following intramuscular administration of 50 mg/kg to dogs.

Peak plasma concentrations of the penicillins occurred within half an hour after administration with the peak lymphatic concentrations occurring 1.5 to 3 h afterwards. For the remaining period of the test the concentration in the lymph exceeded the corresponding concentration in the plasma. Sulphadiazine gave concentrations in thoracic lymph equal to the plasma concentration, but the peripheral lymph concentrations were lower while the concentrations of chloramphenicol in both peripheral and thoracic lymph were always lower than the plasma concentrations.

After the peak concentrations were reached, the concentration curves for penicillins in lymph followed the same pattern as found in plasma, the penicillin concentrations declining exponentially. Sulphadiazine produced more persistent levels both in lymph and in plasma while the concentrations of chloramphenicol were still rising 6 h after administration.

The free concentrations of penicillin in lymph were equal to the free concentrations in plasma, whereas the concentrations of free sulphadiazine and chloramphenicol in lymph were less than those in the plasma.
The effect of acute administration of (meta trifluoro methyl‐phenyl)‐l‐(benzoyl oxy) ethyl amino‐2‐propane (780 SE) and fenfluramine on human sleep
Authors: Firth H. , Lewis S. A. , Ogunremi O. O. , Oswald I.
Published: July 2012

In contrast to other amphetamine derivatives, fenfluramine (40 mg) and 780 SE (300 mg) had no effect on the rapid eye movement (REM) phase of sleep. Like other amphetamines they disturbed sleep, increasing the number of shifts to stage 1 (drowsiness) and stage W (arousal).
Protection against burn, tourniquet and endotoxin shock by histamine, 5‐hydroxytryptamine and 5‐hydroxytryptamine derivatives
Authors: MARKLEY K. , SMALLMAN ELIZABETH , THORNTON S. W.
Published: July 2012

5‐Hydroxytryptamine (5‐HT), tryptamine, 5‐methyltryptamine, 5‐methoxytryptamine, N‐methyltryptamine, 5‐hydroxy‐N,N‐dimethyltryptamine, and histamine markedly protect mice subjected to burn, tourniquet and endotoxin shock. All of these compounds protect when given 30 min before the production of shock, but not when administered afterwards.

The above compounds, as well as purines and purine derivatives have a similar chemical structure. Protection requires the compounds to contain a 5‐membered ring with one unsubstituted N atom and a side chain with a basic N atom three atoms from the ring.

All other biological amines tested without this chemical structure did not protect.

Since the simplest compound containing all the prerequisites for protection is histamine, this compound may play the key role in protection, for both 5‐HT and purines release histamine from tissues.

Protective doses of 5‐HT and histamine prevent swelling of the injured area after tourniquet trauma and produce an increased bleeding volume and lower haematocrit value after burning. These actions of the drugs on the circulation may account for the increased survival after thermal trauma.
Uptake of nicotine and extracellular space markers by isolated rat ganglia in relation to receptor activation
Authors: BROWN D. A. , HALLIWELL J. V. , SCHOLFIELD C. N.
Published: July 2012

Uptake of 3H‐nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically.

Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5·3 × 10−6m.

Both ganglia accumulated nicotine when incubated in 3·1 × 10−5m 3H‐nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean ± s.e. of mean): SCG, 3·49 ± 0·13; NG, 2·50 ± 0·09.

Total water contents, estimated by drying to constant weight, were: SCG, 83·8 ± 0·12%; NG, 80·1 ± 0·21%. Extracellular spaces, measured as 3H‐mannitol space, were: SCG, 38·8 ± 1·3; NG, 40·3 ± 0·8% wet weight. These values were not significantly altered by nicotine.

Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for 3H‐nicotine at 3·1 × 10−5m were: SCG, 7·4; NG, 5·6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3·1 × 10−7 and 1·6 × 10−4m.

When the nicotine concentration was sufficiently great (6·2 × 10−6m or more) to evoke large SCG depolarizations, hexamethonium (2·5 × 10−3m) reduced 3H‐nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6·2 × 10−6m, hexamethonium did not modify uptake by either ganglion.

It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.
Inotropic actions of lignocaine and phenytoin
Authors: KENNEDY BARBARA L. , NOOKHWUN CHONGKOL , SADAVONGVIVAD CHIRAVAT , TANCHAJJA S.
Published: July 2012

The inotropic effects of two antiarrhythmic drugs, lignocaine and phenytoin, were studied in electrically driven isolated rabbit atrial preparations. The time‐effect relationship of each drug was investigated with different concentrations and frequencies of stimulation.

The effects of time of exposure, drug concentration and heart rate on the development of beat alterations (cessation of beat, skipped beat, alternating variation of force of contraction and extrasystole) were also studied.

When the chronotropic effects of both drugs were prevented, the inotropic effects were positive or negative depending on the concentration of drug, time of exposure and frequency of stimulation.

At concentrations higher than those obtained in the blood of man on maintenance doses, alteration of the beat occurred but was consistent with the peak blood concentrations immediately after the injection of standard clinical doses. The time of onset of beat alteration shortened when either drug concentration or frequency of stimulation was increased.

The beat alteration produced by antiarrhythmic drugs can account for various adverse effects associated with their clinical use. These effects include transient ventricular tachycardia and extrasystole during and shortly after injection of drug, ventricular tachycardia, ventricular fibrillation and cardiac arrest due either to excessive dose or to persistent tachyarrhythmia if the dose is not excessive.
Evidence for the presence of α‐adrenoceptors in the central thermoregulatory mechanism of rabbits
Authors: DHAWAN B. N. , DUA P. R.
Published: July 2012

The effects of intracerebroventricular administration of some α‐ and β‐adrenoceptor stimulants and antagonists on the body temperature of rabbits were investigated.

Noradrenaline produced a dose dependent rise in body temperature. Other catecholamines were less active.

The noradrenaline response was blocked by α‐adrenoceptor blocking agents while β‐adrenoceptor antagonists had no effect.

α‐Methyl‐noradrenaline and metaraminol had some hyperthermic effect, but significantly reduced the response of noradrenaline.

The possible presence of α‐adrenoceptors in the central thermoregulatory mechanisms is suggested.
Effect of receptor blocking drugs on the depletion of brain glycogen by amphetamine
Authors: HUTCHINS D. A. , ROGERS K. J.
Published: July 2012

Amphetamine sulphate (5 mg/kg), administered intraperitoneally, reduces the concentration of glycogen in the mouse brain by 25–30% after 30 minutes.

The effect of several receptor blocking drugs on the amphetamine‐induced cerebral glycogenolysis was studied.

dl‐Propranolol (0·25 mg/kg) and pronethalol (10 mg/kg) antagonized the depletion of brain glycogen by amphetamine.

Phentolamine, methysergide, atropine and mepyramine failed to antagonize the amphetamine‐induced glycogenolysis.

d‐Propranolol, chlorpromazine and phenoxybenzamine antagonized the glycogenolytic effect of amphetamine only when administered in sedative doses.

It is concluded that amphetamine‐induced glycogenolysis in the mouse brain may be mediated through a β‐adrenoceptor.
1‐Hydroxy‐3‐amino‐pyrrolidone‐2 (HA‐966): a new GABA‐like compound, with potential use in extrapyramidal diseases
Authors: BONTA I. L. , DE VOS C. J. , GRIJSEN H. , HILLEN F. C. , NOACH E. L. , SIM A. W.
Published: July 2012

The drug HA‐966 (1‐hydroxy‐3‐amino‐pyrrolidone‐2), which chemically resembles the cyclic form of GABA, has been studied for neuro‐pharmacological properties and for effects on the catecholamine content of the corpus striatum.

The acute effects on spontaneous behaviour of rodents included flaccid catalepsy and reversible tranquillization in doses which were 5% or less of the lethal dose. Long lasting depression of the CNS, followed by complete recovery, was produced in the cat and the dog. In the monkey HA‐966 caused periodical sleeping episodes.

The exploratory behaviour and the amphetamine‐induced motor activity in mice were blocked by HA‐966. The toxicity of amphetamine in aggregated mice was only moderately reduced, suggesting that HA‐966 differs from neuroleptics.

Tremors induced by chemical agents (nicotine, zinc and tremorine) were markedly inhibited by HA‐966. The muscarinic effects of tremorine were not reduced by HA‐966, indicating a selective central antitremor effect.

HA‐966 elevated the threshold to strychnine convulsions and abolished the ipsilateral flexor reflex, while not having motor endplate blocking properties. It is suggested that HA‐966 depresses central internuncial neurones.

In rats and rabbits HA‐966 produced synchronous EEG and inhibited the sensory arousal in doses not causing sedation. In the monkey the drug caused a periodical dissociation between ‘sleep‐EEG’ and behaviour.

In rat brain, HA‐966 selectively elevated the dopamine content in the corpus striatum, while no changes in noradrenaline and 5‐hydroxytryptamine contents could be demonstrated. The effect was still present when dopa synthesis was inhibited with α‐methyl‐p‐tyrosine.

Several effects of intravenously administered HA‐966 became manifest after an appreciable delay and in hepatectomized mice the effects were much reduced. It is postulated that HA‐966 is converted to a pharmacologically active metabolite.

The results are discussed in the light of current views on drug therapy in extrapyramidal conditions and a GABA‐related hypothesis as to the mode of action of HA‐966 is presented.
Effect of phenmetrazine, aminorex and (±) p‐chloramphetamine on the motor activity and turnover rate of brain catecholamines
Authors: COSTA E. , NAIMZADA K. M. , REVUELTA A.
Published: July 2012

The minimal doses (μmol/kg i.v.) of phenmetrazine, (±)‐p‐chloramphetamine, and aminorex which increase motor activity are 5·6, 3·5, and 1·5, respectively. We detected stereotype behaviour neither in rats receiving intravenous doses 3 times greater nor in animals injected intraperitoneally with 44, 62 and 112 μmol/kg of (±)‐p‐chloramphetamine, aminorex and phenmatrazine, respectively.

The latter doses of the three amphetamine congeners were tested for their action on tissue monoamine content. Only (±)‐p‐chloramphetamine decreased the concentration of tel‐diencephalon 5‐hydroxytryptamine (5‐HT) and this decrease lasted longer than 24 hours. This and the other two amphetamine congeners failed to affect the concentration of noradrenaline (NA) in brain, heart and lung.

Aminorex (1·5 μmol/kg i.v.) and (±)‐p‐chloramphetamine (3·5 μmol/kg i.v.) decreased the turnover time of striatum dopamine (DM) but failed to change the turnover time of tel‐diencephalon and brainstem NA. Phenmetrazine (5·6 μmol/kg i.v.) changed neither the turnover time of striatum DM nor that of NA in the two brain areas assayed.
Some neurochemical effects of amphetamine, methylamphetamine and p‐bromomethylamphetamine in the rat
Authors: LEONARD B. E. , SHALLICE SUSAN A.
Published: July 2012

Low doses of d‐amphetamine increased brain noradrenaline concentrations in the rat; doses greater than 5 mg/kg, however, caused a decrease. Methylamphetamine also showed this dual effect, but a reduction in brain noradrenaline concentration only occurred when doses greater than 10 mg/kg were administered. p‐Bromomethylamphetamine did not significantly reduce brain noradrenaline concentrations even at a dose of 60 mg/kg. The order of potency in reducing the concentration of noradrenaline correlated with the central stimulant effects; d‐amphetamine produced the greatest and p‐bromomethylamphetamine the least increase in motor activity.

d‐Amphetamine and d‐methylamphetamine potentiated the action of 4,α‐dimethyl‐m‐tyramine (H77/77) in depleting brain noradrenaline; the greatest potentiation was produced by d‐amphetamine. This suggests that the phenylethylamines may affect brain noradrenaline concentrations by acting on the reserpine resistant uptake mechanism.

Differences were found in the effect of the three drugs on brain dopamine concentrations; d‐amphetamine caused a decrease while p‐bromomethylamphetamine caused an increase. Methylamphetamine had no effect on the concentration of dopamine. Only p‐bromomethylamphetamine significantly reduced the depletion of brain dopamine concentrations caused by H77/77.

Methylamphetamine and p‐bromomethylamphetamine reduced the concentration of 5‐hydroxytryptamine (5‐HT) in the brain; administration of the same dose of d‐amphetamine did not change the concentration of 5‐HT.

Changes in the blood and brain concentrations of tyrosine and tryptophan, and in the concentration of γ‐amino‐n‐butyric acid in the brain could not be correlated with the changes observed in the concentrations of biogenic amines in the brain.
Secondary excitation of intestinal smooth muscle
Authors: FURNESS J. B.
Published: July 2012

A period of stimulation of intrinsic or extrinsic nerves to intestinal muscle is often followed by a secondary contraction. In the present work, the basis for such secondary contractions in the longitudinal muscle of the large bowel of guinea‐pigs and rabbits was examined.

In general, the action of cholinergic nerves did not contribute significantly to the secondary contractions. Concentrations of atropine or hyoscine, which completely blocked primary cholinergic contractions, potentiated or did not significantly reduce secondary contractions.

Atropine resistant, nerve mediated primary contractions of the guinea‐pig ileum were inhibited by anticholinesterases, although these drugs potentiated secondary contractions in other segments of the gut.

The occurrence of a secondary contraction following inhibition of smooth muscle activity did not depend on the nature of the initial inhibition. Thus, secondary contractions were observed following the responses to both non‐adrenergic and adrenergic inhibitory nerves, adenosine triphosphate, noradrenaline and brief periods of anoxia. The secondary contractions following hyperpolarizing drugs or anoxia were not prevented by tetrodotoxin in a concentration sufficient to paralyse all nerves.

It is concluded that cholinergic nerves do not contribute significantly to secondary contractions except at frequencies of stimulation higher than about 50 Hz or after the inhibition of cholinesterases. In the segments of gut examined, the secondary contractions were principally myogenic.
Effects of nicotine on salivary amylase secretion from rabbit parotid gland
Authors: INOKI R. , KOJIMA S. , TAMARI Y. , YAMAMOTO I.
Published: July 2012

The effects of nicotine on amylase secretion induced by auriculo‐temporal nerve stimulation were studied.

Nicotine caused a transient increase in secretion as well as flow rate of amylase.

No difference in nicotine action was found between acute sympathetic decentralization of the gland and acute denervation.

The increase in amylase secretion due to nicotine was not inhibited by phenoxybenzamine, bretylium and chronic denervation, but was prevented by hexamethonium, propranolol and adrenalectomy.

The increase in flow rate due to nicotine was not inhibited by propranolol, chronic denervation and adrenalectomy, but was prevented by hexamethonium, phenoxybenzamine and bretylium.

These results show that the action of nicotine in increasing amylase secretion is neither a direct action on the ganglion nor on the nerve terminal of the cervical sympathetic nerve, but is an indirect action of catecholamines released from the adrenal medulla on the post‐junctional receptors.

The study also suggests that the initial acceleration of salivary flow due to nicotine is characterized by a mechanism different from that of amylase secretion.
Some endocrinological aspects of barbiturate dependence
Authors: NORTON P. R. E.
Published: July 2012

Hypophysectomized rats become dependent on barbitone and show the same withdrawal syndrome as intact animals.

Barbitone dependent rats have larger thyroid and adrenal glands, a larger liver, smaller gonads and larger secondary sex organs than untreated animals. The levator ani muscle of the males is smaller.

In contrast, dependent female hypophysectomized rats only showed a decreased gonad weight and increased liver weight.

Histologically, the thyroid gland of dependent rats appears more active, but the concentration of iodine bound to plasma protein, basal metabolic rate and body temperature are similar in dependent and untreated animals.

Resting plasma corticosterone concentration appears to be unchanged in barbitone dependent animals, but stress induced increases in the concentration of corticosterone in plasma are less in dependent animals.

Immature barbitone dependent rats grow at a faster rate than untreated animals, but hypophysectomized rats of similar age receiving barbitone do not.

The additional body weight gained by barbitone dependent animals is of normal body composition.

Administration of growth hormone has an identical growth inducing effect in dependent hypophysectomized animals and in untreated hypophysectomized animals.

Barbitone dependent rats do not exhibit the ‘frustration effect’ in a double runway. In barbitone dependent rats approach to a potentially ‘frustrating’ situation is slower than in untreated animals.