bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pharmacological basis of coronary and systemic vasodilator actions of diazepam (Valium)
Authors: ABEL R. M. , REIS R. L. , STAROSCIK R. N. 
Published: July 2012

Summary
The effects of α and β‐adrenoceptor blockade, depletion of catecholamine stores, vagotomy, atropine, and ganglionic blockade on diazepam‐induced vasodilatation were investigated in forty‐six anaesthetized dogs.
Coronary blood flow was measured by timed collections of coronary venous efflux from fibrillating, decompressed ventricles; coronary and systemic vascular resistances were determined during total cardiopulmonary bypass under conditions of normothermia and constant aortic (coronary artery) pressure.
No significant alteration in the vasodilatation produced by diazepam was observed following either vagotomy or α‐adrenoceptor blockade; partial inhibition of vasodilatation occurred after β‐adrenoceptor blockade or catecholamine depletion, and nearly total inhibition was observed after small doses of atropine or ganglion‐blocking agents.
The results suggest that diazepam may act as a specific ganglion‐stimulant, causing active sympathetic and cholinergic vasodilatation.
Modification by ouabain of the electrical and mechanical effects of acetylcholine in isolated rabbit atria
Authors: KAJIMOTO N. , TODA N. 
Published: July 2012

Summary
Left atrial preparations isolated from rabbits were stimulated electrically at frequencies between 6 and 240/min. Tension‐frequency curves were obtained from control preparations and preparations treated with ouabain and acetylcholine. Transmembrane potentials were recorded from single cells of the left atrium stimulated at different frequencies.
The tension‐frequency curve was moved downwards by acetylcholine (10−6 g/ml). Ouabain (10−6 g/ml) caused characteristic alterations in the tension‐frequency relationship, enhancing the contractile tension at low but not high frequencies. The negative inotropic effect of acetylcholine was reduced by treatment with ouabain.
Action potential durations were significantly influenced by alterations in frequency of contraction. The 10% duration increased with frequency within the range between 6 and 60/min but decreased at frequencies higher than 120/min. The 50% duration increased with frequency between 6 and 120/min but decreased at frequencies higher than 180/min. The dependence of the 50% duration upon frequency paralleled that of contractile tension. The 90% duration, the overshoot and the resting potential were not affected by frequency of contraction.
Acetylcholine (10−6 g/ml) shifted the 10%, 50% and 90% duration‐frequency curves downwards, but did not significantly alter the overshoot and the resting potential. Ouabain (10−6 g/ml) shifted the duration‐frequency curves downwards and also reduced the size of the overshoot and the resting potential. Treatment of atrial preparations with 10−6 g/ml ouabain potentiated the membrane effects of acetylcholine.
The inhibition by ouabain of the negative inotropic effect of acetylcholine did not appear to be due to antagonism at the receptor level, but to interference with the mechanisms responsible for the mechanical events.
Induction of hypovolaemia by thirst‐inducing doses of renin or angiotensin II
Authors: HAEFELI LISETTE , PETERS G. 
Published: July 2012

Summary
Intravenous injection of five Goldblatt units (Gbl.U) of renin, or intravenous infusion of 2·5 μg of angiotensin into nephrectomized rats decreased plasma volume by 22 ± 2% (calculated from the increase of the haematocrit) or by 14 ± 2% (calculated from the increase in protein concentration) within 2 minutes. Fifteen minutes and 60 min after injection or infusion, the plasma volume (calculated from both parameters) was still 10% lower than initially.
The initial discrepancy between haematocrit values and plasma protein concentration was neither due to mobilization of red blood cells (r.b.c.) from the spleen, nor to an increase in r.b.c. volume.
The observed decrease in plasma volume was large enough to explain the drinking response to renin and angiotensin. Renin may thus induce or aggravate hypovolaemia rather than signalling its occurrence to hypothalamic receptors.
Maturation of convulsogenic activity induced by leptazol in the albino rat
Authors: DE CASRILEVITZ MIRA , ENGELHARDT E. , ESBÉARARD C. A. 
Published: July 2012

Summary
Maturation of the excitatory and inhibitory neuromechanisms at various levels of the central nervous system was demonstrated by the convulsogenic activity induced by leptazol in the developing albino rat.
The somatomotor end points considered (myoclonic jerk, myoclonic seizure, tonic seizure and catalepsy) were not observed in all age groups. Tonic seizure was seen at birth, myoclonic jerks at 2 weeks of age, myoclonic seizure and catalepsy at 3 weeks of age.
The convulsive sequences described presented three different patterns, defining three age groups: the infant pattern (infant group: newborn‐1 week old animals); the transitional pattern (transitional group: 2 week old animals); and the adult pattern (adult group: 3 week old—adult animals).
Effective doses were determined for the three types of convulsive sequence: MJ50 for the myoclonic major sequence (maximal end point: myoclonic jerk), MS50 for the myoclonic major sequence (maximal end point: myoclonic seizure) and the TS50 for the myoclonic‐tonic‐clonic sequence (maximal end point: tonic seizure).
The correlation of the convulsive patterns with the dose and latency variations suggests that: (a) the neuromechanisms responsible for the tonic seizure and clonic seizure, located at brainstem and spinal cord levels, function at birth and reach maturity at 3 weeks of age; (b) the neuromechanisms responsible for the myoclonic manifestations and for catalepsy, located at the striato‐thalamocortical level, start functioning at 2–3 weeks of age, indicating the later maturation of the more cephalic structures.
Effects of the muscarinic agonist McN‐A‐343 on responses to sympathetic nerve stimulation in the rabbit ear artery
Authors: RAND M. J. , VARMA B. 
Published: July 2012

Summary
Observations were made on the effects of 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammonium chloride (McN‐A‐343) on responses of isolated segments of the central artery of the rabbit's ear to sympathetic nerve stimulation and noradrenaline.
With low frequencies of nerve stimulation (2–5 Hz), McN‐A‐343 caused a decrease in responses to sympathetic nerve stimulation. This effect of McN‐A‐343 was abolished by dexamphetamine or atropine. In the presence of atropine, McN‐A‐343 caused an increase in responses to sympathetic nerve stimulation.
With high frequencies of nerve stimulation (10–20 Hz), McN‐A‐343 caused an increase in responses. This effect was not qualitatively changed in the presence of atropine.
When McN‐A‐343 had an inhibitory effect on responses to sympathetic nerve stimulation, responses to noradrenaline were unaffected.
It is suggested that McN‐A‐343 acts on muscarinic receptors through which noradrenaline release may be inhibited; it may also act on the cholinergic stage in adrenergic transmission postulated by Burn & Rand (1959).
Turning behaviour as an index of the action of amphetamines and ephedrines on central dopamine‐containing neurones
Authors: CHRISTIE JANICE E. , CROW T. J. 
Published: July 2012

Summary
Rats lesioned unilaterally in the substantia nigra show no obvious abnormalities after recovery from the operation but rotate towards the lesioned side after administration of drugs of the amphetamine and ephedrine groups.
(+)‐Amphetamine and (–)‐amphetamine are equally potent in producing turning behaviour but (+)‐methylamphetamine is considerably more effective.
(–)‐Ephedrine (with a β‐OH group on the ethylamine side chain) induces turning but only in doses approximately 20 times greater than (+)‐methylamphetamine.
(+)‐Norpseudoephedrine was the most effective of the ephedrine isomers tested followed by (–)‐ephedrine and (+)‐pseudoephedrine.
Turning produced by (–)‐ephedrine and (+)‐methylamphetamine is not reduced by FLA63 (50 mg/kg) 4 h previously, but is almost completely inhibited by α‐methyl‐p‐tyrosine (150 mg/kg) 12 h previously.
Reserpine pretreatment potentiates turning produced by (–)‐ephedrine.
Chlorpromazine (5 mg/kg) completely blocks turning induced by (+)‐methylamphetamine although it concurrently increases exploratory activity. The level of exploratory activity after the (+)‐methylamphetamine‐chlorpromazine combination is more than 3 times that attained after saline alone.
Effect of β‐adrenoceptor blocking compounds (propranolol, practolol and LB 46) on isoprenaline induced changes in regional blood flow in the rat
Authors: DEBRECZENI L. , FENYVESI T. 
Published: July 2012

Summary
The effects of three β‐adrenoceptor blocking agents on isoprenaline induced changes in systemic and regional blood flow have been investigated in rats anaesthetized with pentobarbitone. The blood flow to the principal vascular beds was measured by the 86Rb fractionation method.
Isoprenaline infusion at a rate of 0.3 (μg/kg)/min intravenously caused an increase in cardiac output and a decrease in peripheral resistance which affected different vascular fields unevenly. The coronary and carcass fractions of cardiac output increased while the cutaneous, renal and splenic fractions decreased.
Pretreatment with propranolol (2 mg/kg intravenously) blocked all isoprenaline effects. Practolol (8 mg/kg intravenously) lessened the effect on cardiac output but did not prevent the vascular effects except those on the coronary circulation. LB 46 (0.2 mg/kg) had less marked β‐adrenoceptor blocking activity than propranolol (2.0 mg/kg).
Effects of progesterone on cardiovascular responses to amines and to sympathetic stimulation in the pithed rat
Authors: FOZARD J. R. 
Published: July 2012

Summary
Blood pressure and heart rate responses to adrenaline, noradrenaline, tyramine, 5‐hydroxytryptamine and stimulation of the spinal sympathetic outflow were measured in pithed rats pretreated either with progesterone (20 mg/kg daily for 14 days) or the vehicle solution of ethyl oleate.
Pretreatment with progesterone increased the durations but not the magnitudes of the blood pressure and heart rate responses to adrenaline and that phase of the response to sympathetic stimulation attributable to amine release from the adrenal medulla.
Responses to noradrenaline, tyramine, 5‐hydroxytryptamine and that phase of the response to sympathetic stimulation associated with amine release from the sympathetic nerves were not significantly different in the two groups.
Pyrogallol (5 mg/kg) increased the duration but not the magnitude of responses to adrenaline, noradrenaline and sympathetic stimulation in both experimental groups. The increases in duration were consistently less in animals pretreated with progesterone than in controls.
Pretreatment with progesterone did not affect the total amount of radioactivity nor the proportion of catechol to non‐catechol metabolites excreted in the urine during a period of 7.25 h following an intraperitoneal injection of (±) isoprenaline‐7–3H.
It is concluded that the effects of progesterone may result from a localized decrease in catechol O‐methyl transferase activity within the cardiovascular system.
Decarboxylases of histidine and ornithine in chick embryo
Authors: DZODZŒ YAO C. G. , ROSENGREN ELSA 
Published: July 2012

Summary
The activities of histidine and ornithine decarboxylases as well as the histamine content of the developing chick embryo were studied.
Histidine decarboxylase (l‐histidine carboxy‐lyase; E.C. 4.1.1.22) activity was fairly low with a tendency to increase at later stages of development. This enzyme was preferentially present in the supernatant fraction of the tissue homogenate. α‐Methyl‐histidine, but not α‐methyl‐DOPA, inhibited its activity.
The histamine content per gramme of embryo was low with a tendency to increase with the age of the embryo.
Ornithine decarboxylase (l‐ornithine carboxy‐lyase; E.C. 4.1.1.17) activity was high at the beginning of the stages of development investigated, but later there was a steep fall in activity. A noticeable feature was that while the activity in the residual fraction of the homogenate remained almost constant during development, the activity in the supernatant fraction was high in the early stages, then fell rapidly to nearly zero at later stages.
Cardiorespiratory effects of intravenous isoprenaline and salbutamol in dogs
Authors: LOH L. , SEED R. F. , SYKES M. K. 
Published: July 2012

Summary
The cardiorespiratory effects of intravenous infusions of isoprenaline and salbutamol (1 and 5 μg/min) have been compared in twelve dogs.
Both drugs produced a rise in pulse rate, a fall in systemic arterial pressure and a rise in pulmonary arterial pressure. Salbutamol produced a greater increase in cardiac output than isoprenaline.
Both drugs produced an increase in venous admixture, but a significant fall in arterial oxygen tension occurred only with isoprenaline at the higher dose.
Central autonomic effects of prostaglandin F2α on the cardiovascular system of the dog
Authors: LAVERY HELEN A. , LOWE R. D. , SCROOP G. C. 
Published: July 2012

Summary
Prostaglandin F2α infused into the vertebral artery of the anaesthetized greyhound in doses which had no effect when given intravenously ((8–64 ng/kg)/min) caused an increase in blood pressure and heart rate.
This response was not significantly altered by β‐adrenoceptor blockade with propranolol (10 mg i.v.) or by cervical cord section at C4–6.
The tachycardia was abolished and the pressor response greatly reduced by vagotomy or atropine (250 μg/kg i.v.).
The pressor response which remained after vagotomy was abolished by subsequent sympathetic blockade with bethanidine (2–3 mg/kg i.v.) or bretylium (10 mg/kg i.v.).
In contrast to the effects of propranolol or cervical cord section bethanidine (4–5 mg/kg i.v.) or bretylium (10 mg/kg i.v.) significantly reduced blood pressure and heart rate responses to intravertebral prostaglandin F2α. This result suggests that bethanidine and bretylium have some central actions.
It is concluded that the cardiovascular effects of intravertebral infusions of prostaglandin F2α are mediated by the autonomic nervous system and that the preferential pathway is withdrawal of vagal tone to the heart.
Quantitative analysis on isolated organs of the autonomic blocking properties of indoramin hydrochloride (Wy 21901)
Authors: ALPS B. J. , HILL MADELINE , JOHNSON E. S. , WILSON A. B. 
Published: July 2012

Summary
Indoramin is a competitive α‐adrenoceptor blocking agent on the guinea‐pig isolated vas deferens and aortic strip; the pA2 value on the aorta is 7·4.
Indoramin is devoid of β‐adrenoceptor blocking activity on the guinea‐pig isolated trachea (10–4m) and the Langendorff preparation of the rabbit heart (10−6m). It also has no adrenergic neurone blocking action on the Finkleman preparation of the rabbit small intestine (10−5m).
On the Langendorff preparation of the rabbit isolated heart, indoramin (above 10−6m) has cardio‐inhibitory properties similar to those of propranolol.
On the guinea‐pig isolated ileum (10−5m) and trachea (10−6m), indoramin is devoid of anticholinergic activity, but has a potent antihistamine action which satisfies the criteria for competitive antagonism; the pA2 value for this antagonism on the ileum is 8·2.
Indoramin antagonizes 5‐hydroxytryptamine on the rat isolated fundus and ileum; the pA2 value for the antagonism on the ileum is 60.
Effect of β‐adrenoceptor blocking agents on poststimulatory atrial flutter in the dog, with observations on the participation of adrenergic mechanisms in this experimental arrhythmia
Authors: MADAN B. R. , SONI R. K. 
Published: July 2012

SummaryFour β‐adrenoceptor antagonists,viz.(±) propranolol (0·5 mg/kg), (—) alprenolol (0·25 mg/kg), practolol (5 mg/kg) and USVC 6524 (20 μg/kg), were tested for their effects on atrial flutter produced by electrical stimulation of the right atrium around the crushed inter‐venae‐caval bridge in anaesthetized dogs.All the drugs reduced atrial and ventricular rates; this was followed by the abrupt termination of flutter and restoration to normal sinus rhythm.Since all the drugs (including practolol, which is devoid of local anaesthetic activity) were given in doses just sufficient to block β‐adrenoceptors, it indicated that β‐adrenoceptor blockade was responsible for their antiarrhythmic property in this test procedure.Further evidences in support of participation of the sympathetic nervous system in poststimulatory flutter were: (i) flutter could not be produced in nine out of ten dogs whose catecholamine stores were depleted by pretreatment with reserpine; (ii) infusion of adrenaline in these animals resulted in the production of flutter; (iii) duration of flutter after termination of exposure to adrenaline was a few minutes, which is similar to the brief time previously reported to be taken for the disappearance of catecholamines from the hearts of reserpinized animals.The clinical significance of the above findings is discussed.
Some pharmacological properties of piperazine
Authors: MASON P. A. , STURMAN GILLIAN 
Published: July 2012

Summary
The action of piperazine on mammalian smooth, cardiac and skeletal muscles has been studied.
Piperazine increased tone and produced a dose dependent contraction of isolated smooth muscle, which was antagonized by atropine.
With cardiac muscle, piperazine depressed both the rate and force of contraction and was antagonized by atropine. At higher concentrations, a non‐specific depression of cardiac muscle was found. The intravenous injection of piperazine produced a transient decrease in both heart rate and blood pressure and this was followed by an increase.
In about half of the mammalian skeletal muscle preparations, piperazine potentiated the twitch of the muscle evoked by electrical stimulation.
On the frog neuromuscular preparation, piperazine produced potentiation of the twitch but this was followed first by blockade of the effects, of nerve stimulation and then by depression of the effects of direct muscle stimulation.
Developmental characteristics of brain catecholamines and tyrosine hydroxylase in the rat: effects of 6‐hydroxydopamine
Authors: BREESE G. R. , TRAYLOR T. D. 
Published: July 2012

Summary
Brain noradrenaline, dopamine and tyrosine hydroxylase were found in rat brain a few days before birth and increased progressively until reaching adult values. The most rapid period of growth for these substances seemed to occur between 7 and 18 days.
The intracisternal administration of 6‐hydroxydopamine to rats 7 days of age reduced concentrations of noradrenaline, dopamine, and tyrosine hydroxylase by 72 hours.
The concentrations of noradrenaline, dopamine or tyrosine hydroxylase in rats that received 6‐hydroxydopamine at 7 or 14 days of age remained markedly reduced when determined at adulthood, indicating that fibres did not continue to develop after the administration of this compound. The rats treated at 7 days also showed diminished concentrations of noradrenaline in heart.
Rats injected with 6‐hydroxydopamine at 7 days had reduced body weight as well as a reduction of some organ weights. This growth deficit was not observed in animals that received this drug at 14 days of age.
The administration of ovine growth hormone to rats that received 6‐hydroxydopamine at 7 days did not reverse the growth deficiency in these animals.
Long‐lasting peripheral and central effects of 6‐hydroxydopamine in rats
Authors: CLARK D. W. J. , LAVERTY R. , PHELAN E. L. 
Published: July 2012

Summary
In newborn rats treated with 6‐hydroxydopamine hydrobromide (6‐OHDA) (50–150 mg/kg on 5–7 days) a widespread and long‐lasting dose related sympathectomy was demonstrated.
When rats given 6‐hydroxydopamine (100 mg/kg, seven treatments) in the neonatal period were killed at 10 weeks the concentration of noradrenaline (NA) in the heart, mesentery and vas deferens was significantly reduced. There was no alteration in the catecholamine content of the adrenal glands.
The amplitude of the responses of perfused mesenteric arteries from 6‐hydroxydopamine treated rats to intra‐arterial noradrenaline was not increased, compared with controls, but the duration of responses was increased.
6‐Hydroxydopamine given to newborn rats caused a long‐lasting depletion of noradrenaline in three of the five regions of the central nervous system (cortex, cerebellum and spinal cord) studied. The concentration of noradrenaline in the pons‐medulla was increased, but in the thalamic region was unchanged. The treated rats showed significantly lower exploratory activity.
Treatment of newborn rats with 6‐hydroxydopamine thus has striking and long‐lasting effects on peripheral and central adrenergic systems.
Effect of cannabis and certain of its constituents on pentobarbitone sleeping time and phenazone metabolism
Authors: PATON W. D. M. , PERTWEE R. G. 
Published: July 2012

Summary
Cannabis extract prolonged sleeping time in mice in a thermally neutral environment (30–32° C) in which hypothermia does not occur. The prolongation was dose related, just detectable at 50 mg/kg, and 4‐fold at 500 mg/kg.
Under these conditions, ether sleeping time was not prolonged.
Cannabis extract inhibited the aerobic metabolism of phenazone by a microsome‐rich 9,000 g supernatant of mouse liver homogenate capable of nicotinamide adenine dinucleotide phosphate (NADPH) generation.
Δ1‐Tetrahydrocannabinol (Δ1‐THC) prolonged pentobarbitone sleep and inhibited phenazone metabolism, but its action was limited, and could not account for the effect of the extract. The carotenes and water‐soluble fractions of the extract were inactive on pentobarbitone sleep.
Cannabidiol was strongly active by both tests; in vivo 39·8 μm/kg (12·5 mg/kg) prolonged sleep by 190%, and in vitro 12·7 μm inhibited phenazone metabolism 20%. These actions were dose related, and could account for the effect of the extract.
The prolongation of pentobarbitone sleep by cannabis extract in a dose of 200 mg/kg, intraperitoneally, was maximal when given 30 min before the pentobarbitone, still present at 3 h, but undetectable at 24 hours. No phase of enhanced metabolism at 24 or 48 h after single cannabis injection was detected.
It is concluded that cannabis extract inhibits microsomal activity of mouse liver, chiefly by virtue of its cannabidiol content. It is probable that cannabis consumption by man could lead to altered disposal of many other drugs, used in medicine or otherwise.