bluuebunny/crossref_metadata_2025_split huggingface dataset:
The reversal by pyridostigmine of neuromuscular block produced by soman
Authors: French Mary C , Wetherell Janet R , White P D T 
Published: April 2011

Abstract
The effect of pyridostigmine on neuromuscular block produced by soman was studied in the isolated phrenic nerve-diaphragm preparation. In the rat, soman produced an irreversible reduction in tetanic tension and functional acetylcholinesterase (AChE) activity. Pretreatment with pyridostigmine before exposure of the diaphragm to soman, followed by removal of the anticholinesterase from the organ bath, produced a return of tetanic tension and an increase of 5% in functional AChE activity. Similar results were obtained in the guinea-pig. The changes in synaptic AChE activity were verified pharmacologically by showing a decrease in the blocking activity of acetylcholine in preparations pretreated with pyridostigmine in comparison to those given soman alone following removal of the anticholinesterase. The blocking dose of carbachol did not change in these two groups indicating that desensitization was not a component of the protective action. A comparison was also made of the results obtained by measuring inhibition of AChE in situ with those obtained from muscle homogenates. The implications of these results are discussed.
The protection of primates against soman poisoning by pretreatment with pyridostigmine
Authors: Dirnhuber P , French M C , Green D M , Leadbeater L , Stratton J A 
Published: April 2011

Abstract
The effectiveness of pyridostigmine pretreatment against soman poisoning has been determined in rhesus monkeys and marmosets receiving atropine therapy. Pretreatment with the maximum sign-free dose (200 μg kg−1, i.v.) raised the subcutaneous LD50 of soman by a factor of 28 in rhesus monkeys and 15 in marmosets. Theprotection afforded by a quarter of the sign-free dose of pyridostigmine was not significantly less. These levels of protection are higher than any reported in non-primate species.
Comparative metabolism of codeine in man, rat, dog, guinea-pig and rabbit: identification of four new metabolites
Authors: Cone E J , Darwin W D , Gorodetzky C W 
Published: April 2011

Abstract
The metabolism and excretion of codeine and its metabolites in untreated urine of man, rat, dog, guinea-pig and rabbit have been examined. Metabolites were identified by gas chromatography mass spectrometry operated in the chemical ionization mode (methane). Concentrations of codeine and metabolites were measured by selected ion monitoring. Both codeine and norcodeine were detected in the urine of all species but a new metabolite, hydrocodone, was found only in the urine from man, guinea-pig and dog. Additional metabolites (presumably resulting from the metabolism of hydrocodone) were also detected in man and guinea-pig. Overall recoveries of drug and metabolites from untreated urine were low for all species.
N-Chloroacetyl 5-methoxytryptamine (isamide): a selective antagonist of 5-hydroxytryptamine in the rat uterus
Authors: Huidobro-Toro J Pablo , Huidobro F , Ruiz Manuel 
Published: April 2011

Abstract
Isamide, the N-chloroacetyl derivative of 5-methoxytryptamine, produced a dose-dependent competitive blockade of uterine contractions in vitro induced by 5-HT. The pA2 value for the 5-HT-isamide interaction was 4.42. The blockade was short-lasting and reversible; after recovery, a dose-dependent increase in the uterine sensitivity to 5-HT was found. The blockade proved to be selective to the 5-HT receptor. The simultaneous application of 5-HT plus isamide partially prevented the 5-HT-induced auto blockade phenomenon. In addition, isamide did not affect the contractile responses of the uterus to oxytocin or bradykinin or the contractile effects of the rat vas deferens to adrenaline.
Specific membrane-binding of angiotensin II—the role of degradative enzymes
Authors: Moore A F , Povinelli M A 
Published: April 2011

Abstract
The possible role of degradative enzymes was examined in the specific binding of angiotensin II (AII) to cell membranes. Red blood cell membranes did not bind AII specifically under any of the ambient conditions studied, indicating a lack of AII receptors and no role for the degradative enzymes in specific binding. Rabbit aorta smooth muscle cell membranes bound AII specifically, and this binding had similar characteristics to those previously described for this preparation. It is concluded that specific binding of AII to cell membranes does not involve degradative enzymes, and probably represents binding to the biologically active receptor.
Rapid paper chromatographic separation of [14C] angiotensin II from some metabolites: application to organ distribution
Authors: Wagner Lorin A , Blosser William G , Buckley J P 
Published: April 2011

Abstract
A rapid, inexpensive method for the separation of 5-1-isoleucyl[14C] angiotensin II (A-II) from its various metabolites has been devised. A-II was extracted from tissues with absolute methanol (recovery 96%) and paper chromatographed in a butanol-acetic acid-water (18:2:5) medium for two ascents at 60° C. The resulting RF for A-II of 0.45 was then compared with the RF values of three A-II metabolites produced by enzymatic degradation of the 14C-A-II and [14C]isoleucine. Trypsin degradation produced the [14C]hexapeptide metabolite, chymotryptic degradation produced the [14C]tetrapeptide metabolite and carboxypeptidase A degradation produced the [14C]heptapeptide. Increases in temperature produced a continuous increase in RF values for all the substances examined but the resolution decreased above 60° C. Similarly, increases in the temperature caused the appearance of secondary peaks with some but not all peptides. The tryptic digest (hexapeptide) and the chymotryptic digest (tetrapeptide) are apparently acid- and heat-stable under the experimental conditions. All of the peptides examined failed to produce secondary peaks when heated at neutral pH. The method was used to study the tissue distribution of 14C-A-II after intravenous injection.
Synthesis, properties and biological activity of tritiated N-benzylamidino-3,5-diamino-6-chloro-pyrazine carboxamide — a new ligand for epithelial sodium channels
Authors: Cuthbert A W , Edwardson J M 
Published: April 2011

Abstract
A method is described for the synthesis and purification of tritiated N-benzylamidino-3,5-diamino-6-chloro-pyrazine carboxamide (benzamil). The tritium was inserted at the meta position of the benzyl ring, from which it apparently does not exchange with solvent hydrogen. When stored in ethanol at −4°C the radioligand remains stable for at least 15 months. The pharmacology of benzamil is very similar to that of amiloride in terms of its effects on sodium transporting epithelia except that it has a higher affinity. The affinity of benzamil for sodium channels in amphibian epithelia in the absence of sodium is approximately 109 M−1. The new ligand can be used to label sodium channels in epithelia, and may be useful in channel isolation procedures.
A nuclear magnetic relaxation study of bound water in solutions of disodium cromoglycate
Authors: Attiga S A , Eley D D , Hey M J 
Published: April 2011

Abstract
The amount of water bound to disodium cromoglycate (DSCG) in frozen aqueous solutions was determined from the amplitude of the n.m.r. free induction decay. The hydration number was found to be 15 molecules H2O/molecule DSCG of which 6 H2O molecules were less strongly bound than the rest. Proton T1 and T2 relaxation times in non-frozen solutions implied a value of 10−8 s for the correlation time of the bound water at 291 K. This is consistent with the mobility of DSCG molecules in a smectic mesophase.
Sources of variation during collaborative evaluation of in vitro dissolution tests for two solid preparations
Authors: Cartwright A C 
Published: April 2011

Abstract
Collaborative in vitro dissolution tests on a sample of commercial tolbutamide tablets and a sample of oxytetracycline capsules were carried out in eight laboratories. The two preparations tested showed differences between the products in release characteristics, particularly in the disintegration phase. This may have caused the difference in the pattern of variance in the two trials. In the case of tolbutamide tablets the value of the repeatability standard deviation was small, and therefore the major contribution to the variance was in the difference between laboratories. With oxytetracycline capsules the major contribution to the variance lies in the random errors common to all laboratories (i.e. the within-laboratory variance). One major source of inter-laboratory variance was identified as the level of vibration at the side of the dissolution flask. Another source of variation was found to be due to using a stated extinction coefficient instead of comparing the absorbances of the samples to those of a solution of a reference substance.
Analysis of the contractile effect of 5-hydroxytryptamine on the isolated posterior communicating artery of the cat
Authors: Marín J , Salaices M , Marco E J , Gãmez B , Lluch S 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) induced dose-dependent increases in tension on the isolated posterior communicating artery (PCA) of the cat were significantly antagonized by lysergic acid diethylamide (LSD, 6 times 10−9 m). In the presence of phentolamine (10−6 m) the contraction induced by the two lowest doses of 5-HT was significantly reduced. Pretreatment of the animals with reserpine (3 mg kg−1, i.p., total dose) did not modify the dose-response curve to 5-HT except for the lowest dose. Removal of both superior cervical sympathetic ganglia 15 days before the experiment brought about a significant increase in the vasoconstriction induced by 5-HT at all the doses compared with the control. Cocaine (10−6m) induced a significant shift to the left of the dose-response curve to 5-HT but the maximum response was the same as in the control. The augmented response to 5-HT after denervation was partially antagonized by LSD (6 times 10−9 m) but not by phentolamine (10−6 m). These results show that the vasoconstriction elicited by 5-HT in the PCA of the cat is mainly due to direct stimulation of tryptaminergic receptors. The participation of an indirect adrenergic component in the contractile effects of 5-HT seems to be negligible.
The evaluation of the force to expel oily injection vehicles from syringes
Authors: Dexter M B , Shott M J 
Published: April 2011

Abstract
Measurement of the force needed to expel oily injection vehicles from all-glass syringes through hypodermic needles has shown that the force required to maintain various rates of expulsion is in agreement with a modified form of the Poiseuille equation. The flow from disposable plastic syringes with rubber plunger tips fits this equation only if a correction is made to take account of the resistance to movement of the plunger (which is effectively zero for all-glass syringes). This resistance or binding force was shown to be increased by exposure to vegetable oils, and its magnitude was inversely dependent on vehicle viscosity. This increase was caused by swelling of the rubber plunger tips due to uptake of the oily vehicles by the rubber. No such increase in binding force was observed with a viscous aqueous vehicle.
A high performance liquid chromatographic assay of cis- and trans- isomers of tricyclic neuroleptic drugs
Authors: Po A Li Wan , Irwin W J 
Published: April 2011

Abstract
Tricyclic neuroleptics based upon the thioxanthene nucleus exhibit geometrical isomerism and the major pharmacological activity resides in the Z-component. An h.p.l.c. procedure which enables the separation detection and quantification of these isomers is described. The method is applicable to the analysis of flupenthixol, clopenthixol, chlorprothixene, doxepin and dothiepin. Measurement of the isomer-ratios in various samples of flupenthixol has shown that small batch to batch variations are apparent. The determination of the isomer-ratio in formulations has been shown to rely upon the complete extraction of the medicament. This is due to the differential release of the components from the tablet matrix with the cis-isomer being favoured. There is little difference observed between the adsorption isotherms of the two components (onto charcoal) but in competition experiments differential adsorption may be demonstrated. This has clear implications for the pharmacokinetics of these drugs.
The effects of dihydrochandonium and other chandonium analogues on neuromuscular and autonomic transmission
Authors: Apong P Teer , Marshall I G , Harvey A L , Singh Harkishan , Paul Dharam , Bhardwaj T R , Ahuja N K 
Published: April 2011

Abstract
The muscle relaxant chandonium and four of its analogues have been assessed for neuromuscular, ganglion blocking and vagolytic activity in the chloralose-anaesthetized cat, for neuromuscular blocking activity in the chick isolated biventer cervicis and rat phrenic nerve-hemidiaphragm preparations, for muscarinic and histamine blocking activity in the guinea-pig isolated ileum preparation and for effects on adrenergic responses in the rat isolated vas deferens preparation. All five compounds produced neuromuscular block of rapid onset and short duration when given to cats in doses of 5–500 μg kg−1 and produced non-depolarizing competitive neuromuscular blockade in the isolated skeletal muscle preparations. Saturation of the 5–6 androstene bond to produce dihydrochandonium (HS692) resulted in a loss of potency by a factor of 0·5. The NN-diethyl analogue of dihydrochandonium (HS693) was about half as potent as HS692. The triethyl (HS704) and NN-diethyl (HS705) analogues of chandonium possessed one-tenth and one-fifth respectively of the muscle relaxant activity of chandonium. In cats, all compounds inhibited the bradycardia produced by vagal stimulation and by methacholine, the vagolytic effect of HS693 being particularly powerful and long-lasting. Although the compounds did not block the depressor response to methacholine in vivo, all the compounds inhibited responses to carbachol in the guinea-pig isolated ileum. However, from pA2 values the compounds were found to be 10–100 times more active at nicotinic than at muscarinic receptors. None of the compounds had histamine-blocking activity, ganglion-blocking activity, or actions on adrenergic responses.
Elimination of prostacyclin (PGI2) and 6-oxo-PGF1α in anaesthetized dogs
Authors: Salmon John A , Mullane Kevin M , Dusting Gregory J , Moncada Salvador , Vane John R 
Published: April 2011

Abstract
The plasma concentration of 6-oxo-PGF1α was measured by radioimmunoassay after constant rate infusion of 6-oxo-PGF1α or prostacyclin (PGI2) into anaesthetized dogs. A steady-state plasma concentration was rapidly attained with both compounds. After termination of the infusions, the concentration of 6-oxo-PGF1α declined according to a bi-exponential process. The steady-state plasma concentrations of 6-oxo-PGF1α obtained after infusion of 6-oxo-PGF1α and PGI2 were approximately 10 times higher than the corresponding steady-state level of PGF2α measured after infusion of PGF2α into the same dogs. The data presented suggest that PGI2 and 6-oxo-PGF1α are eliminated more slowly than PGF2α, probably because they are not taken up and metabolized in the lungs as rapidly as PGF2α.
Factors underlying the variable inotropic effect of ouabain on isolated rat atria. Changes in contractile frequency and adrenergic mechanisms
Authors: Gimeno Alvaro L , Sterin-Borda Leonor , Borda Enri S , Gimeno Martha F 
Published: April 2011

Abstract
The effects of concentrations of ouabain on the isometric developed tension (IDT) of isolated left auricles driven at 0·4, 0·8 and 3·3 Hz, were explored. With 0·4 or 0·8 Hz, increasing concentrations of ouabain (3·4 or 6·8 times 10−6; 1·0; 3·4 or 6·8 times 10−6M) elicited a decreasing enhancement of atrial contractile peak tension, whereas with 3·3 Hz the effect was augmented with concentration. Ouabain (3·4 times 10−6 M) enhanced comparably the IDT at all the driving rates, but at higher concentrations the effect varied with the frequency. The positive inotropic action of ouabain at 3·4 times 10−6 M on preparations driven at faster frequencies was antagonized by Sotalol (MJ-1999) and also after catecholamine depletion by in vivo reserpinization followed by addition of tyramine in vitro. Cocaine or U-0521 significantly enhanced the positive inotropic effect of ouabain (3·4 times 10−5 M) in atria stimulated at low rates. On the contrary, Sotalol, cocaine, U-0521 or catecholamine depletion did not alter the positive inotropic influence of ouabain at 3·4 times 10−6 M at any of the frequencies used. It is suggested that ouabain influenced contractile peak tension of rat isolated atria through two mechanisms: one, seen after higher concentrations, which appeared to be associated with adrenergic factors and dependent on the frequency of stimulation; the other, observable with the lower concentrations, which did not appear to have a direct relationship with adrenergic processes and which was independent of the frequency of stimulation.
Cardiovascular studies with impromidine (SK&F 92676), a new very potent and specific histamine H2-receptor agonist
Authors: Owen D A A , Harvey Carol A , Gristwood R W 
Published: April 2011

Abstract
Impromidine (SK & F 92676) has recently been identified as a potent and specific histamine H2-receptor agonist. The present paper describes some cardiovascular studies with the drug. Impromidine lowers blood pressure in cats and rats by interaction with H2-receptors. During continuous intravenous infusions of impromidine, the fall in blood pressure is due to a reduction in total peripheral resistance; cardiac output increases during hypotension. The responses to impromidine are similar to responses to histamine in mepyramine-treated cats. Impromidine administered intra-arterially also causes vasodilatation in the femoral and mesenteric vasculature by interaction with H2-receptors. Impromidine stimulates all measured parameters including coronary flow in the isolated working heart of the guinea-pig. Dose-response curves to impromidine were displaced to the right in the presence of cimetidine.
Anti-inflammatory and platelet anti-aggregant activity of phospholipase-A2 inhibitors
Authors: Vallee E , Gougat J , Navarro J , Delahayes J F 
Published: April 2011

Abstract
Mepacrine, papaverine, p-bromophenacyl bromide and 2,3-dibromo(4′-cyclohexyl-3′-chloro)-phenyl-4-oxo-butyric acid (CB 874) inhibit the hydrolysis of phospholipids induced by thrombin in dog platelets. They also exhibit anti-inflammatory and anti-aggregant properties. These biological activities may be explained by a direct or indirect inhibitory action on phospholipase A2. Phospholipase A2 inhibitors may block not only the release of arachidonic acid and its subsequent conversion into prostaglandins but also the formation of lysophospholipids involved in inflammation and/or platelet aggregation.
The rapid development of functional tolerance to ethanol by mice
Authors: Grieve Susan J , Littleton John M 
Published: April 2011

Abstract
A method is described in which the development of tolerance to ethanol in individual mice can be measured during the inhalation of ethanol vapour. This method has been used with two behavioural end-points, loss of righting reflex and loss of rotarod performance. It demonstrates that, in the adult male, TO Swiss mouse, peak tolerance, in which approximately 2 × the original effective blood ethanol concentration is required to produce the behavioural end-point, can develop in 3–5 h. After this time the ability of the animals to perform normally in the presence of continued high concentrations of ethanol in blood begins to fall. The results are discussed in relation to current concepts of tolerance to central nervous system depressant drugs.
Aspirin-caffeine interaction in the rat
Authors: Collins Catherine , Laird R I , Richards P T , Starmer G A , Weyrauch Solveig 
Published: April 2011

Abstract
Both aspirin at a high dose (400 mg kg−1) and caffeine (5 mg kg−1) induced hyperactivity in the DA rat, but lower doses of aspirin were without effect. Caffeine-induced hyperactivity was brief (2 h) but that due to aspirin was evident from 1–6 h after dosing. Co-administration of the two drugs caused long-lasting hyperactivity, even with doses of aspirin which had no stimulant effects themselves. Absorptive and metabolic effects did not appear to play a major role in the interaction. The most likely effect is that of salicylate on catecholamine utilization in the central nervous system, which is compounded in the presence of a phosphodiesterase inhibitor.
The use of phospholipid liposomes for lithium administration. Polydipsic effect and tissue distribution of lithium
Authors: Zilberman Yael , Lichtenberg Dov , Gutman Yehuda 
Published: April 2011

Abstract
Administration of lithium entrapped in phospholipid liposomes increased the lithium-induced polydipsia, but did not accelerate the onset of this effect. It also resulted in a larger accumulation of lithium in the liver, kidney and spleen, but not in the brain. The time course of polydipsia suggests that it depends on the intracellular lithium concentration. However, the rate of development of this effect depends on some additional factor.
The effect of 2-substitution on conformations and brain concentrations of phenothiazine-neuroleptics in relation to dopamine-antagonism
Authors: Grol Cor J , Rollema Hans , Asselbergs Hans W 
Published: April 2011

Abstract
Conformational energies of promazine, chlorpromazine and triflupromazine were calculated with the INDO-method and plotted as a function of two torsion angles. Distance maps were constructed for the N-S and N-2-substituent distances and compared with the N-O distances in dopamine in its preferred conformation, demonstrating the flexibility of the phenothiazine molecules, and showing that interactions with various dopamine-receptor sites, are likely. To eliminate the influence of transport and distribution on the activity, rat brain concentrations of the phenothiazines were determined simultaneously with the increase in striatal homovanillic acid (HVA) concentrations. Concentrations causing a 300% rise in HVA (taken as a measure of neuroleptic activity) were compared with i.p. doses inducing the same rise in HVA, showing that relative potencies based on brain concentrations and relative potencies obtained from i.p. doses were virtually equal. As the increase in lipophilicity does not significantly improve penetration into the brain, it is concluded that the enhancing effect of 2-substitution on the neuroleptic activity might be due to (a) the increase in the probability of conformations in which the side chain is directed towards one side of the molecule and (b) to a direct interaction with the receptor at a site corresponding with one of the dopamine oxygens.