bluuebunny/crossref_metadata_2025_split huggingface dataset:
The continuous bioassay of the release and disappearance of histamine in the circulation
Authors: FERREIRA S. H. , NG K. K. , VANE J. R. 
Published: July 2012

Summary
The blood‐bathed organ technique was used for the continuous assay of histamine in circulating blood.
Longitudinal strips of cat or kitten terminal ileum detect concentrations of histamine of 2–5 ng/ml; these are below the threshold at which hypotension is induced in dogs.
The cat or kitten terminal ileum also contract to bradykinin. However, the simultaneous use of a cat jejunum strip, which is selectively sensitive to bradykinin, will distinguish between histamine and bradykinin.
The utility of the method for detecting and quantitating circulating histamine was exemplified by measuring: (a) its half‐life in the circulation, (b) its disappearance during a passage through the vascular beds of lungs, liver and lower limbs, and (c) its release into the circulation by compound 48/80.
A CENTRAL VASODEPRESSOR EFFECT OF DYFLOS
Authors: EDERY H. , GUERTZENSTEIN P.G. 
Published: July 2012

Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 μl.
The topical application of dyflos (1–20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration.
Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect.
The two reactivators of acetylcholinesterase, obidoxime (100–200 mg/ml) and pralidoxime mesylate (100–200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect.
Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied.
The problem is discussed as to whether the reversal of the dyflos and carbachol‐induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine‐like action of these compounds or to a combination of both.
METABOLISM OF ISOPRENALINE AFTER AEROSOL AND DIRECT INTRABRONCHIAL ADMINISTRATION IN MAN AND DOG
Authors: BLACKWELL E.W. , BRIANT R.H. , CONOLLY M.E. , DAVIES D.S. , DOLLERY C.T. 
Published: July 2012

Administration of isoprenaline by aerosol inhalation to man results in over 80% being metabolized to the sulphate conjugate.
The majority of an inhaled dose is probably swallowed since the metabolic pattern resembles that after an oral dose.
Isoprenaline, administered in aqueous solution directly into the bronchial tree in both man and dog, is rapidly O‐methylated to 3‐O‐methyl isoprenaline, which is subsequently conjugated with sulphate.
3‐O‐Methylation is the main metabolic pathway for the small part of an inhaled dose which does enter the bronchial tree.
POTENCY AND SELECTIVITYin vitroOF COMPOUNDS RELATED TO ISOPRENALINE AND ORCIPRENALINE ON β‐ADRENOCEPTORS IN THE GUINEA‐PIG
Authors: O'DONNELL STELLA R. , WANSTALL JANET C. 
Published: July 2012

Amines related in structure to either isoprenaline (catechol series) or orciprenaline (resorcinol series) were examined for activity on isolated trachea (relaxation), atria (chronotropic action) and perfused hind‐limb (vasodilatation) of the guinea‐pig.Compounds with a resorcinol nucleus were less potent on all three preparations but more selective for trachea than were compounds with a catechol nucleus.In both catechol and resorcinol compounds potency on trachea was enhanced by and selectivity for trachea was favoured by substitution of ap‐OH phenyl group in theN‐isopropyl, or by replacement of theN‐isopropyl with anN‐t‐butyl, with or without ap‐OH phenyl group.Most of the compounds, particularly the resorcinols, had much lower potencies, relative to isoprenaline, on hind‐limb than on trachea.Some of the problems associated with the quantitative measurement of selectivity and with sub‐classification of β‐adrenoceptors are discussed.
FURTHER OBSERVATIONS ON THE CARDIOTOXICITY OF ISOPRENALINE DURING HYPOXIA
Authors: McDEVITT D.G. , SHANKS R.G. , SWANTON J.G. 
Published: July 2012

In dogs respired with 10% oxygen: 90% nitrogen, only five out of 16 dogs survived repeated intravenous doses of isoprenaline (either 0.5 or 1.0 μg/kg) and only one out of six dogs survived repeated isoprenaline inhalations from a pressurized aerosol.In dogs respired with 15% oxygen: 85% nitrogen, five out of six dogs survived repeated intravenous doses of isoprenaline (2.5 μg/kg).The fatal response in these animals consisted of a fall in heart rate, arterial and pulse pressures. Sinus rhythm persisted even after the arterial pressure had fallen, though occasionally a slow A‐V nodal rhythm or irregular ventricular ectopic beats occurred. Ventricular fibrillation did not occur.Eight out of 10 dogs brought to the verge of a fatal response with 10% oxygen: 90% nitrogen and repeated doses of isoprenaline (2.5 μg/kg) were resuscitated by the administration of 100% oxygen and, when necessary, cardiac massage.A group of five dogs survived the combined effects of repeated doses of isoprenaline (2.5 μg/kg) and respiration with 10% oxygen: 90% nitrogen when the time interval between doses was 11 min, instead of the usual 5 minutes.Control of pH by infusion of sodium bicarbonate did not protect the dogs from the combined effects of hypoxia and repeated isoprenaline challenge.After a 60 min period of continuous isoprenaline infusion in dogs breathing room air, only one of 10 dogs survived artificial respiration with 10% oxygen: 90% nitrogen and repeated challenge with intravenous isoprenaline (1.0 μg/kg) at 5 min intervals. At the higher infusion levels of isoprenaline (0.1 and 1.0 μg kg−1min−1), two dogs out of four died after the hypoxic mixture was started but before any isoprenaline challenge was given.The possible relevance of these findings in dogs to the recently observed increase in mortality in young asthmatics is discussed.
A COMPARISON OF THE ACTIONS OF SOME DRUGS ON DECEREBRATE RIGIDITY, MUSCLE SPINDLE ACTIVITY AND α‐ADRENOCEPTORS
Authors: MAXWELL D.R. , SUMPTER EILEEN A. 
Published: July 2012

The relative potencies of methotrimeprazine, (+)‐methotrimeprazine, (±)‐10‐(3‐dimethylamino‐2‐methylpropyl)‐2‐valeroyl phenothiazine hydrochloride (M & B 18,706) and (+)‐M & B 18,706 in reducing the pressor action of noradrenaline in the spinal cat, reducing intercollicular decerebrate rigidity, and muscle spindle afferent activity have been studied.
Methotrimeprazine was eight times as potent as (+)‐methotrimeprazine in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity. M & B 18,706 was also eight times as potent as (+)‐M & B 18,706 in reducing the pressor action of noradrenaline and six times as potent in reducing decerebrate rigidity.
For the above compounds and chlorpromazine there was a significant correlation between the effective doses for the inhibition of the pressor action of noradrenaline and for the reduction of decerebrate rigidity.
The doses which reduced decerebrate rigidity were similar to those that reduced muscle spindle afferent discharge. It is likely that these drugs reduce decerebrate rigidity by inhibiting fusimotor activity.
Desipramine increased decerebrate rigidity and increased spindle afferent discharge.
It is thought that the phenothiazine derivatives studied reduce decerebrate rigidity and spindle afferent discharge by inhibiting receptors for noradrenaline in the central nervous system.
A PHARMACOLOGICAL STUDY OF THE ADRENERGIC MECHANISMS INVOLVED IN THE STRETCH REFLEX OF THE DECEREBRATE RAT
Authors: COMMISSIONG J.W. , SEDGWICK E.M. 
Published: July 2012

The effects of catecholamine precursors, enzyme inhibitors, and monoamine depletors have been studied on the stretch reflex in the decerebrate rat.
l‐DOPA alone had a biphasic effect, facilitation followed by inhibition and recovery of the reflex.
About 10% of the preparations did not develop decerebrate rigidity. These preparations did not have a stretch reflex. Within 1 to 5 min of the injection of l‐DOPA in these inactive preparations, a stretch reflex could be elicited.
Control experiments indicate that l‐DOPA was acting centrally after decarboxylation.
dl‐dihydroxyphenylserine had an inhibitory effect, without a preceding facilitation.
When l‐DOPA was preceded by diethyldithiocarbamate (i.v.) or FLA‐63 (i.p.), the predominant response was a sustained facilitation, without an accompanying inhibition.
It is concluded that in the decerebrate rat, increased stretch reflex activity is associated with increased central levels of dopamine, and decreased stretch reflex activity with increased central levels of noradrenaline. The results are discussed with reference to the possibility that dopamine acts by liberating 5‐hydroxytryptamine.
THE ROLE OF PROSTAGLANDINS IN RABBIT MONOARTICULAR ARTHRITIS
Authors: BLACKHAM A. , FARMER J.B. , RADZIWONIK H. , WESTWICK J. 
Published: July 2012

Old English (OE) rabbits produced more severe monoarticular arthritis (MAA) after sensitization and intra‐articular challenge with ovalbumin than did either New Zealand White (NZW) or Dutch rabbits. NZW rabbits were better responders than Dutch rabbits.
The swelling of the joint in all three strains of rabbits was triphasic. There was an initial acute swelling which appeared to peak at 2–4 days after challenge. This was followed by a decrease in joint size, and then a secondary increase in size beginning 1–2 weeks after challenge.
An investigation of MAA in OE rabbits showed that there was an increase in E‐type prostaglandins, total leucocyte counts and free acid phosphatase activity in the synovial fluid of the challenged joints at 6 h, 19 h, 47 h, 7 days and 46 days following challenge. There were also histopathological changes at these times. In addition, there was an increase in the surface temperature of both the challenged and non‐challenged knees, and a rise in the body temperature.
Prostaglandin levels peaked at 19 h and were equivalent to 19 ng E2 per joint. In a separate experiment, the prostaglandin present at 18 h was shown to be mainly E1. Maximum levels of prostaglandin appeared to coincide with maximum joint temperature, but preceded maximum joint swelling and a significant rise in both the number of inflammatory cells and the free acid phosphatase activity in the synovial fluid, all of which occurred at 47 hours.
Indomethacin, 7.5 mg/kg orally twice daily, almost completely inhibited the increase in prostaglandin levels in the challenged joints and produced a moderate reduction in joint swelling. It also reduced the increased surface temperature of both knee joints and the raised body temperature. However, indomethacin had no effect on the number of leucocytes present, the free acid phosphatase levels, or the histopathological changes in the joint.
The mean plasma level of indomethacin ranged from 0.5 to 3 μg/ml at the time when the animals were killed.
Lysosomal enzymes may be more important than prostaglandins in rabbit MAA, and the lack of effect of indomethacin on joint histopathology may be due to its inability to prevent the release of these enzymes.
THE ACTIONS OF A NEW β‐ADRENOCEPTOR BLOCKING DRUG, ICI 66082, ON THE RABBIT PAPILLARY MUSCLE AND ON THE DOG HEART
Authors: HARRY J.D. , KNAPP M.F. , LINDEN R.J. 
Published: July 2012

The actions of 4‐(2‐hydroxy‐3‐isopropylaminopropoxy) phenyl acetamide (ICI 66082), a new β‐adrenoceptor blocking drug, on the twitch response of the isolated papillary muscle of the rabbit and on dP/dt max and free heart rate of a denervated dog heart preparation, are described.
ICI 66082 (up to 1 mg/ml) did not produce any depression of the twitch response of the rabbit papillary muscle. ICI 66082 antagonized the action of isoprenaline on this preparation at a concentration of 0.01 μg/ml.
ICI 66082 (0.5–1.0 mg/kg intravenously) reduced the control value of dP/dt max in four dog preparations by a mean value of 529 mmHg/s (s.e. mean ± 139 mmHg/s), with no significant change in free heart rate. Antagonism of the effect of isoprenaline on dP/dt max and on free heart rate was demonstrated with ICI 66082 (0.1 mg/kg).
ICI 66082 (1.0–1.5 mg/kg) produced no significant changes in dP/dt max or in free heart rate in four dogs pretreated with reserpine. A significant reduction (16% of the control value) in dP/dt max was observed with ICI 66082 at a high dose of 40–50 mg/kg.
It is concluded that ICI 66082 is a competitive antagonist against the actions of isoprenaline on cardiac muscle, has no negative inotropic action (unless the dose exceeds 40 mg/kg) and lacks intrinsic sympathomimetic activity.
EFFECTS OF PROPRANOLOL ON GASTRIC SECRETION IN ALBINO RATS
Authors: DEBNATH P.K. , GODE K.D. , DAS D. GOVINDA , SANYAL A.K. 
Published: July 2012

Effects of graded doses of propranolol have been studied on gastric secretion and gastric ulcers in pylorus‐ligated rats.
A dose‐dependent action of propranolol was observed; small doses increased total volume, acid output and pepsin secretion along with an increase in the incidence of ulcers but high doses were inhibitory.
MODIFICATION BY DRUGS OF THE SECRETAGOGUE EFFECT OF DOPAMINE ON THE PANCREAS
Authors: FURUTA Y. , HASHIMOTO K. , ISHII Y. , IWATSUKI K. 
Published: July 2012

The specific stimulating action of dopamine and l‐DOPA on exocrine pancreatic secretion was further investigated in the isolated blood‐perfused canine pancreas.
6‐Hydroxydopamine (100 μg, i.a.) stimulated the secretion but was far less potent than dopamine. Epinine (0.3–1 mg. i.a.), α‐methyldopamine (10–300 μg, i.a.) and octopamine (10–300 μg, i.a.) were ineffective.
α‐Methyldopa (30 mg, i.a.) inhibited the stimulating effect of l‐DOPA (1–3 mg) on pancreatic secretion.
Apomorphine (1 mg, i.a.) attenuated dopamine‐induced (1–30 μg) pancreatic secretion but did not antagonize secretin‐induced (0.03–0.3 units) or pancreozymin‐induced (0.3–1 units) secretion.
These observations suggest that l‐DOPA is probably converted to dopamine to stimulate the exocrine pancreas, and that dopamine interacts with the specific receptors.
The noradrenaline and dopamine content of the canine pancreas was estimated in controls and in dogs treated with secretin, reserpine, l‐DOPA or α‐methyldopa. The values for dopamine and noradrenaline in controls were 139 ± 6 and 375 ± 40 ng/g tissue (n = 13), respectively. Reserpine reduced the noradrenaline content of the pancreatic tissue without affecting the dopamine content. l‐DOPA or secretin caused a significant increase in the dopamine, but not in the noradrenaline content. It is suggested that dopamine has a physiological function in the pancreas which is independent of that of the noradrenaline‐containing nerve fibres.
THE NATURE OF THE BINDING BETWEEN LSD AND A 5‐HT RECEPTOR: A POSSIBLE EXPLANATION FOR HALLUCINOGENIC ACTIVITY
Authors: BERRIDGE M.J. , PRINCE W.T. 
Published: July 2012

(+)‐Lysergic acid diethylamide (LSD) mimicked 5‐hydroxytryptamine (5‐HT) in its ability to stimulate fluid secretion, to change transepithelial and intracellular potentials as well as to increase the cyclic 3′,5′‐adenosine monophosphate (cyclic AMP) concentrations of isolated salivary glands of Calliphora.
Unlike 5‐HT, LSD disengages slowly from the receptor and fluid secretion continues despite repeated washing.
Both 5‐HT and tryptamine prevented LSD from acting on the glands.
LSD bound to the receptor was slowly displaced when glands were treated with agonists (tryptamine) or antagonists (gramine).
The property of LSD which permits it to function as an agonist despite remaining tightly bound to the receptor is discussed as a possible basis for its profound effects within the central nervous system.
MODIFICATION OF RESPONSES TO SYMPATHETIC NERVE STIMULATION BY THE RENIN‐ANGIOTENSIN SYSTEM IN RATS
Authors: JOHNSON E.M. , MARSHALL G.R. , NEEDLEMAN P. 
Published: July 2012

Angiotensin I (AI) and AII elicited a dose‐dependent potentiation of contractions by rat vas deferens produced by low frequency nerve stimulation without enhancing the contraction produced by exogenous noradrenaline. The All‐induced presynaptic potentiation was blocked by the specific antagonist cysteine8‐AII.
The vasoconstrictor response to periarterial stimulation of rat isolated perfused kidney was potentiated by AII and there was a lesser enhancement of the effect of exogenous noradrenaline.
The response to stimulation of complete sympathetic outflow from the spinal cord to blood vessels in the pithed rat was enhanced by angiotensin or vasopressin in direct proportion to the increase in prestimulus muscular tone. The blood pressure in the pithed rats is primarily maintained by the renin‐angiotensin system since the converting‐enzyme inhibitor (SQ‐20881) or bilateral nephrectomy caused further substantial lowering of systemic blood pressure after spinal cord destruction and after treatment with curare and atropine.
ACTIONS OF PUTATIVE TRANSMITTERS IN THE CHICKEN VAGUS NERVE/OESOPHAGUS AND REMAK NERVE/RECTUM PREPARATIONS
Authors: BARTLET A.L. 
Published: July 2012

Histamine (0.02–0.1 μg/ml) contracted the chicken rectum preparation. This effect was antagonized by mepyramine (0.01 μg/ml) but not by hyoscine (0.02 μg/ml).
5‐Hydroxytryptamine (0.05–0.25 μg/ml) relaxed the rectum preparation and at higher concentration produced a biphasic response. These responses were not antagonized by methysergide (0.01 μg/ml), and the relaxation was not antagonized by tetrodotoxin (0.1 μg/ml) or a combination of propranolol (0.05 μg/ml) and phentolamine (0.1 μg/ml).
Neither mepyramine (0.1 μg/ml) nor methysergide (0.01 μg/ml) antagonized the contractions produced by nerve stimulation in vagus nerve/oesophagus and Remak nerve/rectum preparations.
5‐Hydroxytryptamine (2 μg/ml) in the presence of methysergide (0.01 μg/ml), inhibited the contractions produced by nerve stimulation in Remak nerve/rectum and vagus nerve/oesophagus preparations.
Adenosine, adenosine 5′‐phosphate (AMP), adenosine 5′‐diphosphate (ADP) and adenosine 5′‐triphosphate (ATP), in order of decreasing potency, produced slow contractions in most oesophagus preparations. The action of ATP in this preparation was antagonized by tetrodotoxin (0.1 μg/ml), hyoscine (0.1 μg/ml) and strychnine (5 μg/ml).
Desensitization of the vagus nerve/oesophagus preparation to ATP did not produce any antagonism of the contractions to nerve stimulation.
Adenosine and AMP produced relaxations and ADP and ATP contractions in the rectum preparation. ATP was about 100 times as potent as ADP in producing fast contractions which were not antagonized by tetrodotoxin, hyoscine or strychnine.
Desensitization of the Remak nerve/rectum preparation to ATP resulted in the contractions to nerve stimulation and acetylcholine being inhibited to the same extent.
Prostaglandin E2 produced slow contractions in the oesophagus and rectum preparations which were not antagonized by tetrodotoxin (0.1 μg/ml). Polyphloretin phosphate (10 μg/ml) antagonized spontaneous movements and responses to prostaglandin E2 in the rectum but not the oesophagus.
Neither polyphloretin phosphate (60 μg/ml) nor indomethacin (20–100 μg/ml) antagonized the contractions produced by nerve stimulation in vagus nerve/oesophagus (with hyoscine in the bathing solution) and Remak nerve/rectum preparations.
These experiments seem to exclude histamine, 5‐hydroxytryptamine, adenosine and its nucleotides and prostaglandin E2 as possible motor transmitters in synapses and neuromuscular junctions in the chicken vagus nerve/oesophagus and Remak nerve/rectum preparations.
THE EFFECT OF PROSTAGLANDIN E2 ON THE ARTERIAL BLOOD PRESSURE OF NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: SIMPSON L.L. 
Published: July 2012

In anaesthetized rats, injection of prostaglandin E2 (0.5–5.0 μg/kg i.v.) caused a dose‐dependent vasodepressor response. The magnitude of response was significantly greater in spontaneously hypertensive rats than in normotensive rats.
In spontaneously hypertensive rats, the magnitude of the prostaglandin‐induced depressor response was closely correlated with blood pressure. The higher the blood pressure, the greater was the response evoked by prostaglandin.
In spontaneously hypertensive rats, a combination of guanethidine plus hydralazine reduced both blood pressure and prostaglandin‐induced depressor responses.
Spontaneously hypertensive rats and normotensive rats did not differ in the magnitude of their vasodepressor responses to intravenously administered acetylcholine or isoprenaline.
EFFECTS OF BENZOCTAMINE AND CHLORDIAZEPOXIDE ON TURNOVER AND UPTAKE OF 5‐HYDROXYTRYPTAMINE IN THE BRAIN
Authors: LIPPMANN W. , PUGSLEY T.A. 
Published: July 2012

Benzoctamine, a new psychoactive drug, known to exert in man an anti‐anxiety effect resembling that of chlordiazepoxide, decreased the disappearance of intraventricularly‐injected [14C]‐5‐hydroxytryptamine (5‐HT) from rat brain, as did chlordiazepoxide.
Both drugs partially inhibited the α‐ethyl‐3‐hydroxy‐4‐methylphenylethylamine‐induced depletion of rat brain 5‐HT.
It is concluded that benzoctamine, like chlordiazepoxide, decreases 5‐HT turnover in the brain and that this action may play a role in the anti‐anxiety effect of these drugs observed in man.
STRUCTURE‐ACTIVITY RELATIONS FOR THE INHIBITION OF 5‐HYDROXYTRYPTAMINE UPTAKE BY TRICYCLIC ANTIDEPRESSANTS INTO SYNAPTOSOMES FROM SEROTONERGIC NEURONES IN RAT BRAIN HOMOGENATES
Authors: HORN A.S. , TRACE R.C.A.M. 
Published: July 2012

The inhibitory effects of various analogues of imipramine on [3H]‐5‐hydroxytryptamine (5‐HT) uptake into homogenates of rat hypothalamus were examined.
For structures with a three carbon side chain the tertiary amine derivative was more potent than the compound with a secondary amine function.
Potency was reduced by increasing or decreasing the length of the three carbon side chain by one carbon atom.
Substitution of a methyl group in the α or β position in the side chain reduced potency.
Replacement of the dimethylene bridge in imipramine by a sulphur atom or substitution of a C=C double bond for the exocyclic N‐C bond of imipramine both led to a fall in potency.
3‐Chlorimipramine was the most potent inhibitor of [3H]‐5‐hydroxytryptamine uptake of the compounds tested.
EFFECTS OF PROCAINE AND LIGNOCAINE ON ELECTRICAL AND MECHANICAL ACTIVITY OF SMOOTH MUSCLE OF SHEEP CAROTID ARTERIES
Authors: JACOBS A. , KEATINGE W.R. 
Published: July 2012

Procaine in concentrations up to 20 Mm facilitated or induced electrical and mechanical activity in arterial smooth muscle, even with tetrodotoxin present.
Procaine (up to 20 Mm) caused relaxation when electrical activity was blocked by prior potassium depolarization.
Procaine (1 Mm) reduced mechanical responses to noradrenaline (1 μm) which were not accompanied by action potentials. It generally reduced mechanical responses to noradrenaline (1 Mm) while increasing electrical activity induced by this.
Lignocaine (1 Mm) did not facilitate electrical activity significantly; it relaxed arteries in saline or potassium‐rich solution and reduced mechanical responses to noradrenaline.
High concentrations of procaine (at least 80 Mm) or lignocaine (at least 20 Mm) blocked electrical activity and caused contraction followed by relaxation and complete unresponsiveness.