bluuebunny/crossref_metadata_2025_split huggingface dataset:
STIMULANT PROPERTIES OF BROMOCRIPTINE ON CENTRAL DOPAMINE RECEPTORS IN COMPARISON TO APOMORPHINE, (+)‐AMPHETAMINE AND l‐DOPA
Authors: JOHNSON A.M. , LOEW D.M. , VIGOURET J.M. 
Published: July 2012

The activity of bromocriptine has been investigated in tests for the stimulation of central dopaminergic mechanisms. The results obtained have been compared with those of apomorphine, (+)‐amphetamine and l‐DOPA.
Bromocriptine (2.5 to 10 mg/kg) induced stereotyped sniffing and licking in rats. The stereotypy was more intense than that induced by L‐DOPA and less intense than that of apomorphine and (+)‐amphetamine over the dose ranges studied.
In rats lesioned unilaterally in the substantia nigra by local injection of 6‐hydroxydopamine, bromocriptine, like apomorphine and l‐DOPA, induced turning contralateral to the side of the lesion. The smallest dose of bromocriptine to induce turning was 0.5 mg/kg.
Reserpine‐induced catalepsy in mice was antagonized by bromocriptine, with an ED50 of 1.8 mg/kg. It was intermediate in potency to apomorphine and l‐DOPA.
Spontaneous locomotor activity in mice was stimulated by bromocriptine in a dose‐dependent manner from 2.5 to 10 mg/kg after an initial suppression of activity.
In all experiments, bromocriptine was characterized by a prolonged duration of activity after a delay in the onset of effect.
The stereotyped behaviour induced by bromocriptine was inhibited by prior administration of pimozide, reserpine or α‐methyl‐p‐tyrosine.
Bromocriptine‐induced turning behaviour was abolished by pretreatment with pimozide, and reduced after α‐methyl‐p‐tyrosine pretreatment.
The results obtained support the conclusion that bromocriptine acts by stimulating dopamine receptors in the central nervous system and that intact catecholamine synthesis and granular amine storage mechanisms are necessary for it to bring about its effects.
THE UPTAKE AND SUBCELLULAR DISTRIBUTION OF RADIO‐LABELLED METABOLITES OF DIGITOXIN IN THE GUINEA‐PIG ISOLATED PERFUSED HEART
Authors: DUTTA S. , MARKS B.H. , STEPHEN P.M. 
Published: July 2012

Comparisons were made of the uptake and inotropic effects of concentrations of 0.1 μm of digitoxin and its cleavage products digitoxigenin‐bis‐digitoxoside, digitoxigenin‐mono‐digitoxoside and digitoxigenin in the isolated perfused hearts of guinea‐pigs.
Digitoxin produced the greatest inotropic responses in this series, while the sequence of cleavage products produced progressively smaller responses.
The uptake of digitoxin was significantly higher than that of the three metabolites, and the uptake of metabolites became progressively less with cleavage. The highest binding in each case was found in the microsomal fraction.
The uptake of all four digitaloids was reduced when the potassium in the perfusion medium was increased.
PERIPHERAL EFFECTS OF FENFLURAMINE
Authors: MITCHELL G.E.D. , MOTTRAM D.R. 
Published: July 2012

The peripheral cardiovascular effects of the centrally acting anorexigenic agent, fenfluramine hydrochloride, have been investigated in the rat.
After intravenous administration of fenfluramine, an immediate hypotensive response, followed by a reflex rise in blood pressure was recorded. This was followed by a prolonged fall in blood pressure which frequently failed to return to pre‐drug levels.
The antagonists, propranolol and atropine, failed to inhibit this hypotensive effect of fenfluramine.
The effects of 5 mg/kg fenfluramine for 1 h on the blood pressure responses to the sympathomimetic amines, tyramine, methoxamine and metaraminol were studied.
The responses to the indirectly acting tyramine were reduced by 50% following fenfluramine, while those to the directly acting methoxamine remained unaffected by the drug. Responses to metaraminol, an amine with both direct and indirect actions, were also unaffected to a significant degree by fenfluramine.
Studies on rat isolated vas deferens again showed that responses to tyramine are greatly reduced following fenfluramine.
In addition fenfluramine itself produced spontaneous contractions of the vas deferens. These contractions were blocked by the α‐adrenoceptor blocking agents phentolamine and thymoxamine.
It is suggested that fenfluramine exerts an effect at the adrenergic nerve terminal, either by displacing noradrenaline stores or by inhibition of the amine uptake process.
COMPOUNDS DESIGNED TO FIT A SITE OF KNOWN STRUCTURE IN HUMAN HAEMOGLOBIN
Authors: BEDDELL C.R. , GOODFORD P.J. , NORRINGTON F.E. , WILKINSON S. , WOOTTON R. 
Published: July 2012

The three‐dimensional coordinates of the atoms in human haemoglobin are known, and there is a specific site in the deoxygenated form of the protein at which 2,3‐diphosphoglycerate (DPG) interacts.
Molecular models of this site have been constructed and used to design compounds which should bind to the deoxy conformation and stabilize it. These compounds should thereby promote oxygen liberation, as does DPG.
The compounds so designed were found to promote oxygen liberation. Their relative potencies, as assessed by sigmoidal dose‐response curves, are in the predicted sequence.
INDOMETHACIN‐INDUCED ALTERATIONS IN CORTICOSTEROID AND PROSTAGLANDIN RELEASE BY ISOLATED ADRENOCORTICAL CELLS OF THE CAT
Authors: LAYCHOCK SUZANNE G. , RUBIN R.P. 
Published: July 2012

The effects of purported prostaglandin synthesis inhibitors on steroid and prostaglandin (E and F) release from trypsin‐dispersed cat adrenocortical cells were investigated.
Low indomethacin concentrations potentiated adrenocorticotrophin (ACTH)‐evoked prostaglandin and steroid release, whereas higher concentrations depressed both responses to ACTH. The steroidogenic response to exogenous prostaglandin E2 was not markedly altered over a wide range of indomethacin concentrations.
Indomethacin enhanced basal steroid release but did not enhance basal prostaglandin E or F release.
5, 8, 11, 14‐Eicosatetraynoic acid (ETA) elicited a concentration‐dependent inhibition of ACTH‐induced steroid release, but had little effect on prostaglandin E2‐induced steroid release. A high concentration of ETA inhibited prostaglandin E and F release.
These data are discussed in relation to the concept that prostaglandins provide a critical link in ACTH‐induced corticosteroidogenesis.
DEPRESSION BY MORPHINE OF EXCITATORY JUNCTION POTENTIALS IN THE VAS DEFERENS OF THE MOUSE
Authors: HENDERSON G. , NORTH R.A. 
Published: July 2012

Intracellular recordings were made from smooth muscle cells of the mouse vas deferens. Excitatory junction potentials (e.j.ps) were evoked by stimulation of the intramural nerves.
Normorphine (50 nm‐5 μm) depressed the amplitude of the e.j.p. The ED50 was 430 nm. The latency of the e.j.p. and the resting membrane potential of the smooth muscle cells were unaffected by normorphine.
The depression of the e.j.p. by narcotic analgesic drugs was stereospecific.
Naloxone (100 nm) completely reversed the depression of the e.j.p. produced by normorphine (1 μm). Naloxone (100 nm) alone did not alter the amplitude of the e.j.p.
Normorphine (1 μm) did not prevent the depolarization of the smooth muscle cells produced by exogenous noradrenaline (10 μm).
It is concluded that narcotic analgesic drugs act directly upon the transmitter release sites to reduce the amount of noradrenaline liberated by each nerve impulse.
THE CONTRIBUTION OF EXTRANEURONAL UPTAKE TO THE TRACHEA‐BLOOD VESSEL SELECTIVITY OF β‐ADRENOCEPTOR STIMULANTS in vitro IN GUINEA‐PIGS
Authors: O'DONNELL STELLA R. , WANSTALL JANET C. 
Published: July 2012

The potencies relative to isoprenaline of isoetharine, tertiary butyl noradrenaline, salbutamol, orciprenaline, Me 506, rimiterol, fenoterol, carbuterol and terbutaline on isolated preparations of guinea‐pig trachea and blood vessels (perfused hind limb) were determined. All the compounds were selective for trachea and selectivity values, i.e. relative potency on trachea divided by relative potency on hind limb, ranged from 2.3 to 21.4.
Responses to isoprenaline (the reference compound), tertiary butyl noradrenaline and isoetharine were potentiated on trachea by 50 μm phenoxybenzamine (PHB) and by other inhibitors of extraneuronal uptake (ENU). Under these conditions the selectivity values of all the compounds was close to unity.
Selectivity values were also close to unity if they were calculated from data obtained without ENU inhibition, provided that only those compounds not potentiated by PHB on trachea were used.
It is proposed that the trachea‐blood vessel selectivity shown by β‐adrenoceptor stimulants can be caused by the influence of ENU upon them, rather than by their ability to distinguish between two β2‐adrenoceptors.
The suggestion that differences exist between β2‐adrenoceptors in respiratory and vascular smooth muscle is not supported by the in vitro experiments described.
THE INTERACTION BETWEEN ANTHELMINTIC DRUGS AND HISTAMINE IN Ascaris suum
Authors: PHILLIPS JEAN L. , STURMAN GILLIAN , WEST G.B. 
Published: July 2012

Piperazine reduced the histamine content of Ascaris suum, yet it greatly increased the uptake of histamine from the surrounding medium, the neuromuscular structures of the nematode preferentially increasing in amount.
Bephenium reduced the histamine content of Ascaris and the uptake of histamine from the surrounding medium. However, the relative amount in the neuromuscular structures increased.
The flaccid paralysing action of piperazine may thus involve increased histamine absorption whereas the spastic paralysing action of bephenium may be independent of histamine.
INFLUENCE OF DOPAMINE AND NORADRENALINE ON ISOLATED CEREBRAL ARTERIES OF THE DOG
Authors: TODA N. 
Published: July 2012

Effects of dopamine and noradrenaline were compared in helically‐cut strips of canine cerebral arteries.
Dopamine caused a greater maximal contraction than noradrenaline, although the ED50 for noradrenaline was appreciably less. The contraction induced by these amines was reversed to a relaxation by treatment with phenoxybenzamine.
Relaxation induced by dopamine in phenoxybenzamine‐treated and prostaglandin‐contracted cerebral arteries was not influenced by 1 μm propranolol, while relaxation induced by noradrenaline at low concentrations (2 μm and 10 μm) was significantly attenuated. Neither aminophylline nor atropine affected the relaxant effect of dopamine.
A mechanism other than β‐adrenergic, cholinergic or adenosine‐related appears to be involved in the relaxation elicited by dopamine in cerebral arterial strips.
A COMPARISON BETWEEN THE HYPOTHERMIA INDUCED BY INTRAVENTRICULAR INJECTIONS OF THYROTROPIN RELEASING HORMONE, NORADRENALINE OR CALCIUM IONS IN UNANAESTHETIZED CATS
Authors: METCALF G. , MYERS R.D. 
Published: July 2012

The hypothermia produced by intraventricular injections of thyrotropin releasing hormone (TRH) in unanaesthetized cats has been investigated.
TRH is more potent than either noradrenaline or calcium ions. It is estimated that the equi‐potent molar ratio for TRH: noradrenaline: calcium is 1:900:27,000.
TRH injections also produce profuse salivation, tachypnoea, cutaneous vasodilatation and frequently defaecation and vomiting. It is considered that the increased respiration is a major cause of the hypothermia.
Prior administration of phentolamine antagonized noradrenaline‐induced hypothermia but did not affect hypothermia produced by TRH or calcium ions. Pretreatment with α‐methyltyrosine did not affect the hypothermia induced by TRH, calcium ions or noradrenaline.
The calcium antagonists verapamil and xylocaine did not antagonize hypothermia induced by an injection of calcium ions.
The constituent amino acids of TRH did not produce hypothermia either individually or collectively. Thyroxine sodium produced a rise in temperature that was slow in onset, consistent with its known metabolic effects. TSH produced a small hypothermia unrelated to dose.
LONG‐TERM EFFECTS OF N‐2‐CHLOROETHYL‐N‐ETHYL‐2‐BROMOBENZYLAMINE HYDROCHLORIDE ON NORADRENERGIC NEURONES IN THE RAT BRAIN AND HEART
Authors: ROSS S.B. 
Published: July 2012

N‐2‐Chloroethyl‐N‐ethyl‐2‐bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long‐term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5‐hydroxytryptamine (5‐HT) in various brain regions.
In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC50 value of 2 μm but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5‐HT uptake in a cortical homogenate.
DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks.
DSP 4 (50 mg/kg i.p.) caused a decrease in the dopamine‐β‐hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2–4 days was noted. In brain the DBH‐activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced.
The long‐term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.).
It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate.
MYOCARDIAL UPTAKE OF DIGOXIN IN CHRONICALLY DIGITALIZED DOGS
Authors: STEINESS EVA , VALENTIN N. 
Published: July 2012

The time course of myocardial uptake of digoxin, increase in contractility and changes in myocardial potassium concentration was studied for 90 min following an intravenous digoxin dose to long‐term digitalized dogs.
Nineteen dogs were investigated by the use of a biopsy technique which allowed sampling before and after administration of digoxin.
Ten minutes after administration of digoxin the myocardial concentration increased from 60 to 306 nmol/kg tissue; the myocardial concentration of digoxin was significantly lower (250 nmol/kg tissue) after 30 min and then increased again.
The transmural myocardial distribution of digoxin was uniform before and 90 min after administration of digoxin in long‐term digitalized dogs but at 10 min after administration, both the subepicardial and the subendocardial concentration of digoxin were significantly lower than that of the mesocardial layer.
During the first 10 min the dp/dtmax increased to 135% of the control level. The increase remained unchanged during the rest of the study.
Myocardial potassium decreased throughout the study.
The M‐configuration of the myocardial uptake curve and the non‐uniformity of myocardial distribution of digoxin observed at 10 min after administrating digoxin to long‐term digitalized dogs indicate that the distribution of myocardial blood flow may be changed during chronic digitalization.
ANTAGONISM BY SOME ANTIHISTAMINES OF THE AMINO ACID‐EVOKED RESPONSES RECORDED FROM THE LOBSTER MUSCLE FIBRE AND THE FROG SPINAL CORD
Authors: CONSTANTI A. , NISTRI A. 
Published: July 2012

The effects of some antihistamines on the lobster muscle fibre and the frog spinal cord were investigated using intracellular and extracellular recordings, respectively.
On lobster muscle, histamine H1‐blockers reversibly antagonized responses to bath‐applied glutamate, aspartate and quisqualate but not responses to γ‐aminobutyric acid (GABA). Iontophoretic glutamate potentials were also reduced. Histamine (up to 1 mm) had no effect on this preparation.
The H1‐antagonists produced a small increase in muscle membrane conductance and a slight hyperpolarization. These effects were largely unchanged in a low Cl− bathing solution. Procaine (1 mm) decreased membrane conductance and did not affect responses to GABA or glutamate.
The H2‐antagonist burimamide blocked both glutamate and GABA‐evoked responses on the lobster muscle without affecting resting potential or conductance.
In the frog cord, bath‐applied histamine produced ventral root depolarizations and dorsal root hyperpolarizations (sometimes biphasic responses). These effects were reduced by tetrodotoxin (TTX) but not by antazoline (H1‐blocker) or burimamide; the latter reversibly antagonized responses to both glutamate and GABA on TTX‐treated cords while antazoline was ineffective.
It is suggested that antihistamines can act as non‐specific amino acid antagonists by interacting at the level of the receptor‐coupled ionophores.
OESTROGENIC, ANTI‐OESTROGENIC AND FERTILITY EFFECTS OF SOME TRIPHENYLETHANES AND TRIPHENYLETHYLENES RELATED TO ETHAMOXYTRIPHETOL (MER 25)
Authors: CLARK E.R. , JORDAN V.C. 
Published: July 2012

Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and anti‐oestrogenic activity in mice, and three of the compounds, α‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐α‐phenyl‐β‐4‐methoxyphenyl‐ethanol (IV), α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐bibenzyl (V) and α′‐[4‐(β‐diethylaminoethoxy)‐3, 5‐xylyl]‐4‐methoxy‐stilbene (VI), were tested for their effects on fertility in mice.
Orthomethylation reduces oestrogenic and/or anti‐oestrogenic activity compared with the reported activities of non‐methylated analogues.
The anti‐oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti‐oestrogens, V and VI, did not affect fertility in mice.
STEREOSPECIFIC ACTIONS OF 2,5‐DIMETHOXY‐4‐METHYLAMPHETAMINE (DOM) ON COLONIC TEMPERATURE IN THE RAT AT VARIOUS AMBIENT TEMPERATURES
Authors: BEATON J.M. , BENINGTON F. , BRADLEY R.J. , KUHLEMEIER K.V. , MORIN R.D. 
Published: July 2012

The R(—) and S(+)‐isomers of 2,5‐dimethoxy‐4‐methylamphetamine (DOM) produce a dose‐dependent hypothermia in rats kept in the cold (6°C).
This hypothermia was linearly dependent upon ambient temperature and the R(—)‐isomer was considerably more potent than the S(+)‐isomer.
A statistically significant tachyphylaxis was observed when R(—)‐DOM was administered on two successive days. The response seven days after the second injection was similar to that on the first day of injection.
The hypothermia induced by R(—) and S(+)‐DOM was antagonized by methysergide but not by p‐chlorophenylalanine (PCPA) or pimozide. Methysergide, PCPA or pimozide alone did not elicit hypothermia at the doses used. The results indicate that R(—) and S(+)‐DOM act at post‐synaptic 5‐hydroxytryptamine receptors.
PREVENTION BY ZINC OF CADMIUM‐INDUCED ALTERATIONS IN PANCREATIC AND HEPATIC FUNCTIONS
Authors: MERALI Z. , SINGHAL R.L. 
Published: July 2012

Subacute cadmium treatment (CdCl2, 1 mg/kg twice daily for 7 days) in rats disturbs glucose homeostasis as shown by hyperglycemia and decreased glucose tolerance associated with suppression of insulin release, enhancement of hepatic gluconeogenic enzymes and decrease in hepatic glycogen content.
Exposure to cadmium increases hepatic cyclic adenosine 3′,5′‐monophosphate (cyclic AMP) and this is accompanied by stimulation of basal, adrenaline‐as well as glucagon‐stimulated form(s) of adenylate cyclase.
In contrast to cadmium, subacute administration of zinc (ZnCl2, 2 mg/kg twice daily for 7 days) fails to alter the activities of hepatic gluconeogenic enzymes, cyclic AMP synthesis, as well as glucose clearance and insulin release in response to a glucose load.
Zinc, when administered at the same time as cadmium, prevents the cadmium‐induced lesions in both hepatic and pancreatic functions.
The results are discussed in relation to the possible mechanisms of cadmium toxicity and to the role of sulphydryl groups in the protection exercised by zinc.
RECEPTORS FOR 5‐HYDROXYTRYPTAMINE AND NORADRENALINE IN RABBIT ISOLATED EAR ARTERY AND AORTA
Authors: APPERLEY EIRA , HUMPHREY P.P.A. , LEVY G.P. 
Published: July 2012

5‐Hydroxytryptamine (5‐HT) is thought to be implicated in the vascular disturbances of the external carotid artery bed associated with migraine. As part of a study of the pharmacology of some 5‐HT antagonists used in the treatment of migraine we have examined the interactions of these drugs with 5‐HT and noradrenaline in rabbit isolated ear artery and aortic strip. The results provide new information on the distribution of 5‐HT‐receptors and α‐receptors in these preparations.
In the aorta, 5‐HT and noradrenaline were of similar potency in producing contractions. Methysergide produced very small contractions and was about 1000 times less potent than the other two agonists.
In the ear artery noradrenaline produced monophasic vasoconstrictor responses, whereas 5‐HT and methysergide produced prolonged biphasic responses. 5‐HT was about 700 times less potent and methysergide about 4500 times less potent than noradrenaline. Methysergide was a better agonist in the ear artery than in the aorta. Biphasic responses to 5‐HT and methysergide were also obtained in ear arteries from reserpine‐treated rabbits indicating that neither agonist was acting by releasing endogenous noradrenaline.
Pizotifen, cyproheptadine and phentolamine had no agonistic actions in either the aorta or ear artery.
In the aorta methysergide, pizotifen and cyproheptadine were potent antagonists of 5‐HT and much weaker antagonists of noradrenaline. Phentolamine possessed the opposite profile of selectivity. These results show that there are distinct receptors for 5‐HT and noradrenaline in rabbit aorta.
In the ear artery the pA2 values for each of the four antagonists were virtually identical against 5‐HT and noradrenaline and similar to those obtained on α‐adrenoceptors in the aorta. We conclude that 5‐HT and noradrenaline act directly at α‐receptors to produce vasoconstriction in the ear artery and that this preparation does not contain specific 5‐HT‐receptors.
This insight into the distribution of 5‐HT‐receptors and α‐receptors allows interpretation of the various actions of methysergide. In the aorta, methysergide was a potent antagonist at 5‐HT‐receptors and a weak partial agonist at α‐receptors. In the ear artery, methysergide was a partial agonist at α‐receptors; it was only a weak antagonist of 5‐HT because this preparation does not contain specific 5‐HT‐receptors.
The cross‐reactivity demonstrated throughout these experiments indicates that 5‐HT‐receptors and α‐receptors, although distinct entities, have features in common.
These results are discussed in relation to the mode of action of methysergide, pizotifen and cyproheptadine in the treatment of migraine.
ATROPINE RESISTANCE AND MUSCARINIC RECEPTORS IN THE RAT URINARY BLADDER
Authors: CARPENTER F.G. 
Published: July 2012

The action of an anticholinesterase and an antimuscarinic drug upon nerve‐induced contractions of the rat urinary bladder were examined during transmural stimulation at 20 Hz. Responses were graded in magnitude by limiting the duration of the stimulus trains.
Responses of low magnitude produced by short stimulus trains were unchanged by atropine; however, maximal responses resulting from long stimulus trains were diminished in magnitude and shortened in duration.
Responses of small magnitude elicited by short stimulus trains involve muscarinic receptors in close proximity to the neuroeffector junction and are resistant to atropine.
Maximal responses elicited by long stimulus trains involve ‘junctional’ muscarinic receptors as well as receptors located at the periphery of the junction; the ‘extrajunctional’ receptors are blocked by atropine.
Responses of low magnitude produced by short stimulus trains were unaffected by echothiophate; however, the duration of maximal responses resulting from the long stimulus trains was extended.
The inhibition of cholinesterase did not increase the occupation of muscarinic receptors by the transmitter; however, after large quantities of transmitter were released by the long stimulus trains the association between the receptors and acetylcholine was prolonged.