bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs
Authors: Proppe D. 
Published: June 2007

SUMMARY1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea‐pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks.2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape.3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of 3H‐digoxin. The positive inotropic response occurred in the cat heart‐lung preparation 1·5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues.4. The biological half‐lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2·5 days and 4·1 days, respectively, as determined by the terminal exponential elimination phase, in guinea‐pigs. This terminal phase was attained 6–12, 7–24, and 24–48 h after administration of ouabain, digoxin and digitoxin, respectively.5. The findings reveal that in the guinea‐pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties.6. The biological half‐lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea‐pig closely resemble those found in healthy man.
Pentaerythritol trinitrate and glyceryl trinitrate on intramyocardial oxygenation and perfusion in the dog. Krogh analysis of transmural metabolism
Authors: Howe Burton B. , Weiss Harvey R. , Wilkes Sandra B. , Winbury Martin M. 
Published: June 2007

SUMMARY1. The effect of intravenous pentaerythritol trinitrate and glyceryl trinitrate on left ventricular subepicardial (epi) and subendocardial (endo) Po2 and perfusion were compared in anaesthetized open‐chest mongrel dogs. Tissue Po2 was determined simultaneously at a depth of 3 mm (epicardial) and 9 mm (endocardial) with small platinum electrodes by polarography. In a separate series of dogs tissue perfusion of those regions was measured by hydrogen (H2) clearance using similar electrodes.2. Both nitrates increased endocardial Po2 while epicardial Po2 was not altered. Perfusion was determined at the point of the maximal rise in endocardial Po2 (4–7 min after injection of either nitrate). At that period average coronary artery inflow and epicardial perfusion were decreased but endocardial perfusion was not significantly altered.3. Using the data on Po2, hydrogen clearance and intercapillary distance, the effect of the nitrates on transmural metabolism (oxygen consumption) was estimated by Krogh analysis. Basal endocardial metabolism was 20–30% higher than epicardial metabolism. The nitrates reduced metabolism in each region. The absolute decrease in oxygen consumption was greater in the endocardium.4. The results show that both pentaerythritol trinitrate and glyceryl trinitrate improve endocardial oxygenation by producing a more favourable balance between perfusion and oxygen requirements in that region.
PLASMALEMMAL CALCIUM IN CARDIAC EXCITATION‐CONTRACTION COUPLING
Authors: Lüllmann Heinz , Peters Thies 
Published: June 2007

SUMMARY1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force.2. In mammalian heart muscle there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z‐ and I‐lines and increase the cell surface by a factor often.3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane.4. A mechanism is discussed which bases the excitation‐contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the membrane.
PROSTAGLANDINS: ANTINOCICEPTIVE EFFECT OF PROSTAGLANDIN E1 IN THE RAT
Authors: Sanyal A. K. , Bhattacharya S. K. , Keshary P. R. , Srivastava D. N. , Debnath P. K. 
Published: June 2007

SUMMARY1. The antinociceptive effect of prostaglandins E1, E2 and F2α was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose‐related antinociceptive activity.2. The antinociceptive activities of equi‐analgesic doses of morphine (7.5 mg/kg, i.p.) and PGE1 (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p‐chlorophenylalanine), methysergide and 5,6‐dihydroxytryptamine.3. Prostaglandin F2α (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE1.4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia.5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE1‐induced potentiation of subanalgesic dose of morphine.6. The results suggest that, in albino rats, PGE1‐induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE1?) and 5‐hydroxyindole acetic acid, the serotonin metabolite.
PLASMA LEVELS FOLLOWING SINGLE INTRAVENOUS, ORAL AND MULTIPLE ORAL DOSAGE IN NORMOTENSIVE AND HYPERTENSIVE SUBJECTS
Authors: Barnett A. J. , Bobik A. , Carson V. , Korman J. S. , McLean A. J. 
Published: June 2007

SUMMARY1. The pharmacokinetics of methyldopa after oral and intravenous administration was studied in hypertensive and normotensive patients. After intravenous administration methyldopa plasma concentrations decayed according to a two‐compartment open model.2. For intravenous administration the overall elimination constant Ke1 was 0.56 ± 0.03 h−1, the volume of distribution of the central compartment 0.29±0.08 1 kg−1 and the plasma clearance rate 11.2±0.6 1 h−1.3. Plasma half‐times during the β‐phase of the methyldopa plasma decay curve following intravenous and oral administration were 2.8±1.3 and 2.1±0.7 h, respectively.4. Maximal plasma levels in hypertensive out‐patients show great variation and range from 0 to 1.9 μg ml−1.5. No relationships were found between maximal methyldopa plasma levels in patients under treatment and control of hypertension.
BETA‐ADRENOCEPTOR‐MEDIATED EFFECTS OF CLENBUTEROL (NAB 365) ON TRACHEA, HEART AND SKELETAL MUSCLE IN ANAESTHETIZED GUINEA‐PIGS
Authors: Bohmer Karin , O'Donnell Stella R. 
Published: June 2007

SUMMARY1. Intravenous injection of clenbuterol (NAB 365) in anaesthetized guinea‐pigs produced decreases in tracheal segment pressure and in soleus muscle contractions and a slight increase in heart rate. These responses were reduced by propranolol.2. Clenbuterol was less potent than isoprenaline on the trachea and soleus muscle and even less potent on the heart. The maximum response to clenbuterol was the same as that to isoprenaline on the trachea and the soleus muscle but it was not more than 30% of that to isoprenaline on the heart. There was no significant difference between the potencies of clenbuterol on the trachea and the soleus muscle.3. The onset of the responses to clenbuterol were slower and the duration of action longer than those to isoprenaline.4. High doses of clenbuterol blocked isoprenaline responses on heart rate.5. Clenbuterol showed selectivity for the trachea and the soleus muscle (β2‐adrenoceptors) as compared with the heart (β1‐adrenoceptors). This could result, at least in part, from its partial agonist activity on the heart.
ANTIARRHYTHMIC DRUGS AND IN VIVO MYOCARDIAL EXCITABILITY IN THE DOG
Authors: Hasin Y. , Rogel S. 
Published: June 2007

SUMMARY1. It has been demonstrated in an earlier study that the threshold for capturing the canine ventricle in situ varies at each time interval during the relative refractory period with a wide range of current levels. Thus, there is no single threshold curve, as is commonly accepted, but rather a range defined by upper limit of threshold (TU) and a lower limit (TL). TU is the minimal current level which always produced a generalized ventricular response. A wide range of lesser current levels produced a local response but with inconsistent propagation throughout the ventricle. TL is the maximal current level which was never able to elicit a generalized response.2. Applying the method used for the determination of these limits, the present study was undertaken to characterize the effect of quinidine, lignocaine, procainamide and verapamil in therapeutic doses on TU and TL.3. It was found that quinidine, lignocaine and procainamide elevated TU and TL during the relative refractory period, but only quinidine did so during diastole as well. Verapamil, however, did not have any significant influence on excitability. Procainamide had the least effect on the absolute refractoriness of the ventricular muscle as judged by the rightward displacement of the TU and TL curves, while quinidine and lignocaine exhibited a significant displacement regarding TU but much less so for TL.4. The proposition is entertained that TL represents true local excitability of the ventricular muscle and TU represents the stimulus needed for propagation throughout the heart during the most unfavourable conditions for such spread.5. Relative changes of TU/TL as a function of TU are considered to express the capability of the locally induced potential to evoke a generalized response: quinidine diminished, procainamide increased, and lignocaine had no effect on this parameter.
THE ACTIONS OF SOME α‐ADRENORECEPTOR AGONISTS AND ANTAGONISTS IN AN ANTINOCICEPTIVE TEST IN MICE
Authors: Bentley G.A. , Copeland I.W. , Starr Jennifer 
Published: June 2007

SUMMARY1. It has been shown that a number of sympathomimetic drugs, administered subcutaneously, have potent antinociceptive activity in the mouse abdominal constriction test. These drugs were found to be equieffective antagonists of the nociceptive action of acetic acid and acetylcholine. Of the drugs tested, clonidine was the most potent, being almost 60 times more active than morphine, whilst noradrenaline and oxymetazoline were approximately three and five times less active respectively than clonidine. Phenylephrine was without effect after doses of 2 mg/kg.2. The regression lines relating the magnitude of the antinociceptive effect of noradrenaline and oxymetazoline to log dose were moved to the right in an approximately parallel manner after subcutaneous administration of piperoxane, 8 and 16 mg/kg. The antinociceptive action of clonidine was also antagonised by piperoxane, but to a lesser extent. Phentolamine had no antagonistic effect on any of these three a‐agonists after subcutaneous doses of 16 mg/kg.3. Oxymetazoline and clonidine, when given by intracisternal injection, were approximately eight‐three and fifty times more potent respectively than by subcutaneous administration, and their antinociceptive action was not antagonized by piperoxane, 16 mg/kg subcutaneously, or 50 μg/kg intracisternally.4. It is postulated that the antinociceptive action of the a‐agonists is due to an effect on α‐adrenoreceptors located on sensory nerve endings in the peritoneum, and that the affinities of these receptors for the α‐agonists and antagonists is different from that shown by either pre‐ or postsynaptic α‐adrenoreceptors. It also appears likely that the antinociceptive action of clonidine and oxymetazoline when given by intracisternal injection involves different mechanisms from their peripheral effects.
COMPARATIVE STUDIES ON THE PHARMACOLOGICAL ACTIONS OF ANTIARRHYTHMIC DRUGS IN ISOLATED RAT PAPILLARY MUSCLE
Authors: Sugimoto J. , Nagata M. , Morita M. 
Published: June 2007

SUMMARY1. The effects of ajmaline, cocaine, phenytoin, lignocaine, procainamide, propranolol, quinidine and trimetazidine on the contractility and the refractory period of isolated rat papillary muscles were compared.2. At the higher concentrations used, all drugs suppressed the contractile tension of the rat papillary muscles.3. The effects of these drugs on the refractory period were compared at concentrations at which the contractile tension was suppressed by 30% of the control. At this point, lignocaine, procainamide, ajmaline and quinidine prolonged the refractory period more than two‐fold while the effects of propranolol and phenytoin were slight, cocaine and trimetazidine had little or no effect.
COMPARATIVE STUDY OF CHRONOTROPIC AND INOTROPIC EFFECTS OF DOPAMINE AND SEVEN DERIVATIVES ON THE ISOLATED, BLOOD‐PERFUSED DOG ATRIUM
Authors: Chiba S. 
Published: June 2007

SUMMARY1. The effects of seven dopamine amino acid conjugated derivatives were compared with those of dopamine on sinus rate and contractile force using the isolated, blood‐perfused dog atrium preparation.2. Each of these dopamine derivatives induced dose‐related positive chronotropic and inotropic effects.3. The positive chronotropic and inotropic effects were obtained with the same rank order of potency for each effect with six of the dopamine derivatives. Their rank order and relative potency (dopamine = 1000) were: N‐Ileu‐dopamine (3)> N‐Glu‐Pro‐dopamine (1) =N‐Ala‐Glu‐dopamine (l)>N‐Gly‐Gly‐dopamine (0.3) = N‐γ‐Glu‐dopamine (0.3)>N‐Gly‐Gly‐Leu‐dopamine (0.1)>N‐Gly‐Gly‐Pro‐dopa‐mine (0.01).4. In doses producing equal positive inotropic effects, the positive chronotropic effect of N‐Gly‐Gly‐Leu‐dopamine was much less than with the other derivatives tested. Its potency compared to dopamine (= 1000) was 0.3 for the inotropic and 0.1 for the chronotropic effect.5. The duration of action of doses of the derivatives producing approximately equal positive inotropic responses was in the order N‐Ileu‐dopamine =N‐γ‐Glu‐dopamine =N‐Gly‐Pro‐dopamine =N‐Ala‐Glu‐dopamine > N‐Gly‐Gly‐dopamine = N‐Gly‐Gly‐Leu‐dopamine =N‐Gly‐Gly‐Pro‐dopamine > dopamine.
PREVENTION OF ACUTE GASTRIC ULCERATION IN THE RAT BY CIMETIDINE, A HISTAMINE H2‐RECEPTOR ANTAGONIST
Authors: Lee S. P. , Tasman‐Jones C. 
Published: June 2007

SUMMARY1. Intraperitoneal injections of cimetidine into rats markedly reduced gastric acid production. When given at a dose of 50 mg/kg body weight, rate of acid production fell from a mean of 2.73 μmol/min (s.d. = 0.32) to a lowest level of 0.81 (s.d. = 0.28): the difference was highly significant (P< 0.005). When given in a dose of 100 mg/kg, the rate of acid production further fell to 0.18 μmmol/min (s.d. = 0.12; P< 0.001).2. Treatment with cimetidine in doses of 100 mg/kg 8‐hourly during a 24 h period of restraint prevented the development of acute gastric ulceration in the rat. Pretreatment with cimetidine also protected against the ulcerogenic effects of intragastrically administered bile or lysolecithin.3. The marked sustained reduction of acid production most probably accounts for the protective effect of cimetidine against ulcer production in the rat stomach.
THE INFLUENCE OF SEROTONIN ON THE MITOTIC RATE IN THE COLONIC CRYPT EPITHELIUM AND IN COLONIC ADENOCARCINOMA IN RATS
Authors: Tutton P. J. M. , Barkla D. H. 
Published: June 2007

SUMMARY1. The mitotic rate in the crypts of Lieberkiihn of the descending colon and in dimethylhydrazine‐induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique.2. Intraperitoneal injection of a small dose (10 jug/kg) of serotonin resulted in an increase in the tumour cell mitotic rate.3. Blockade of serotonin receptors by 2‐bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL‐6‐fluorotryptophan both result in a decrease in the tumour cell mitotic rate.4. Treatment with serotonin, 2‐bromolysergic acid diethylamide and DL‐6‐fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.
INCREASED BILIARY EXCRETION OF OUABAIN INDUCED BY BUCOLOME IN THE RAT
Authors: Kitani K. , Kanai S. , Miura R. 
Published: June 2007

SUMMARY1. Following the intravenous injection of 3H‐ouabain (0.4 or 0.6 mg/100 g body weight) the plasma concentration and biliary excretion of ouabain were compared for control male Wistar rats and rats given bucolome (BC, l‐cyclohexyl‐5‐n‐butyl‐2,4,6,‐trioxoperhydroxypyrimidine, 20 mg/100 g) 40 min before the ouabain injection. In bucolome treated rats, the bile flow rate was 80–90% higher than in control rats and the biliary excretion rate of ouabain for the 40 min post‐injection period was significantly higher in bucolome treated rat groups. The increase was due to an approximately two‐fold increase in the excretion rate in the first 10 min period. On the other hand, plasma concentration of ouabain was significantly higher in bucolome treated rats compared with control rats at corresponding time intervals. Plasma volume as determined by 131I‐labelled albumin dilution was not decreased in bucolome treated rats.2. The results indicated that the significant increase in biliary excretion of ouabain administration was due to the enhancement of the hepatic transport and/or biliary excretion process and not due to an increase in hepatic uptake.
SOME BIOCHEMICAL RESPONSES OF RAT SKELETAL MUSCLE TO A SINGLE SUBCUTANEOUS INJECTION OF A TOXIN (NOTEXIN) ISOLATED FROM THE VENOM OF THE AUSTRALIAN TIGER SNAKE NOTECHIS SCUTA TUS SCUTA TUS
Authors: Pluskal M. G. , Harris J. B. , Pennington R. J. , Eaker D. 
Published: June 2007

SUMMARY1. Some biochemical responses of mammalian skeletal muscle to a single subcutaneous injection of a purified toxin from the venom of the Australian tiger snake, Notechis scutatus scutatus, have been investigated to determine the role of changes in peptide hydrolase enzymes in the muscle wasting caused by notexin administration.2. Within 6 h of injection, serum creatine kinase activity was increased by five‐to ten‐fold, and remained elevated for at least 24 h.3. There was an initial inflammatory response in the muscle adjacent to the site of injection; by 12 h after injection, muscle wet weight increased by 60%.4. After the initial increase, wet weight fell to about 50% of normal at 7 days. Normal wet weight was achieved by 20 days after the injection. Over the period 1–20 days after the injection of the toxin, the changes in wet weight were mirrored by changes in non‐collagen protein content.5. The activities of cathepsin B and acid proteinase were increased following the injection of the toxin. By 2 days after injection, there was a ten‐fold increase in the activity of cathepsin B, and a seven‐fold increase in the activity of acid proteinase. The activity of both enzymes became normal by 20 days.6. Experiments utilizing a variety of cytotoxic drugs suggested that the acid proteinase and cathepsin B are primarily located within invading phagocytic cells.7. The results are discussed with reference to the previously described pathology of toxin‐damaged skeletal muscle.
THE INFLUENCE OF SUBACUTE DYFLOS ADMINISTRATION ON THE SENSITIVITY TO AGONISTS OF LONGITUDINAL AND CIRCULAR MUSCLE PREPARATIONS OF THE GUINEA‐PIG ILEUM
Authors: Mitchelson F. , O'Shea R. A. 
Published: June 2007

SUMMARY1. Changes in the EC50 values to various agonists in longitudinal and circular muscle preparations of guinea‐pig ileum were investigated following daily pretreat‐ment of the animals for 10 days with dyflos (1.2 mg/kg, s.c).2. In the longitudinal muscle no significant change in sensitivity to acetylcholine and potassium chloride was noted following dyflos treatment. Marked subsensitivity to carbachol and histamine was observed.3. In circular muscle a marked supersensitivity to acetylcholine occurred and there was no change in sensitivity to carbachol.4. Dyflos treatment induced an increase in the slope of the log concentration‐response curve and the maximal contractile response obtained to agonists in both longitudinal and circular muscle preparations. An increase in tissue mass was also associated with dyflos pretreatment.5. Subsensitivity development was not attributable to changes in affinity for agonists at the receptor site but rather to changes at the post‐receptor level leading to a nonspecific subsensitivity.
EFFECTS OF ADRENALINE AND ISOPRENALINE ON HEPATIC VENOUS HAEMODYNAMICS AND VENOUS RETURN IN THE DOG
Authors: Cyong J. C. , Horiguchi Y. , Tanaka K. , Itoh H. 
Published: June 2007

SUMMARY1. The effects of adrenoceptor agonists on venous haemodynamics were examined, utilizing the lower half perfusion method in dogs.2. Femoral arterial pressure, central venous pressure, thoracic vena caval flow, abdominal vena caval flow, renal venous flow and femoral venous flow were measured simultaneously using electronic transducers and electromagnetic flow‐meters. Hepatic volume change was monitored by the strain‐gauge arch.3. Single injections of both adrenaline (1.0 μ/kg) and isoprenaline (1.0 μg/kg) intra‐aortically produced an increase in venous return, adrenaline transiently and isoprenaline continuously.4. Epinephrine increased hepatic venous flow, while isoprenaline increased only abdominal vena caval flow.5. These findings suggest that effects of α‐adrenoceptors are more pronounced on the hepatic vein, while on other peripheral veins, effects of β‐adrenoceptors are more pronounced.
THE DENSITY OF ADRENERGIC NERVES AT VARIOUS LEVELS IN THE GUINEA‐PIG LUNG
Authors: O'Donnell Stella R. , Saar Nili , Wood L. J. 
Published: June 2007

SUMMARY1. Guinea‐pig tracheal and lung segments were systematically examined for adrenergic nerves using the fluorescence histochemical technique. Fluorescence in nerves was enhanced with α‐methylnoradrenaline or by pretreating the animals with nialamide.2. There was a progressive decrease in density of fluorescent fibres in airway smooth muscle from the laryngeal end of the trachea, which was densely innervated, to the bronchioles, which contained only occasional fibres. This was despite obvious fluorescence in blood vessels in the lung.3. It is suggested that, if adrenergic nerves are involved in reflex bronchodilatation in this species, they directly control larger airways and other factors, e.g. non‐adrenergic inhibitory nerves, may be important in the control of smaller airways.
DIFFERENTIAL BLOCKADE OF OCTOPAMINE AND DOPAMINE RECEPTORS BY ANALOGUES OF CLOZAPINE AND METOCLOPRAMIDE
Authors: Dougan D. F. H. , Wade D. N. 
Published: June 2007

SUMMARY1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (±)‐octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation.2. Clozapine will attenuate the effects of (±)‐octopamine and (‐)‐α‐methyl octopamine at the octopamine receptor but not the excitatory effects of dopamine at dopamine receptors.3. Clozapine is more potent than its 2‐positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine.4. These data indicate that replacement of the 8‐chloro substituent in the clozapine nucleus with a 2‐chloro substituent decreases the ability of the compound to blockade octopamine receptors. However, the 2‐chloro‐substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors.5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8‐chloro‐substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring.