bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potentiation of neostigmine and pyridostigmine by 4-aminopyridine in the rat
Authors: Miller Ronald D , Dennissen Peter A F , van der Pol Francien , Agoston Sandor , Booij Leo H D J , Crul Jan F 
Published: April 2011

Abstract
The interaction between 4-aminopyridine and neostigmine or pyridostigmine was studied in vivo in the rat sciatic nerve-anterior tibialis preparation using the constant infusion of pancuronium technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine and 4-aminopyridine were 18, 49 and 440 μg kg−1 respectively. The addition of 100 μg kg−1 of 4-aminopyridine, which produced no antagonism by itself, decreased the neostigmine ED50 to 7·4 μg kg−1. The addition of 200 μg kg−1 of 4-aminopyridine, which produced a 30% antagonism by itself, decreased the ED50 of pyridostigmine to 11 μg kg−1. We conclude that both neostigmine and pyridostigmine interact with 4-amino-pyrine synergistically.
The effects of a hydroxyl group on some chemical and biological properties of n-pentyl ammonium salts
Authors: Barlow R B 
Published: April 2011

Abstract
The effects of a hydroxyl group on the activity and affinity of compounds related to n-pentyltrimethylammonium have been studied on the guinea-pig ileum, frog rectus, acetylcholinesterase and on partitioning (Rm) and size (φov, Vm). The hydroxyl group lowered affinity in all tests, confirming the importance of hydrophobic forces in binding to receptors. Activity on the ileum was lowered appreciably but on the rectus only slightly. The effects on Rm did not indicate any interactions between hydroxyl, onium group and water but the apparent size of the hydroxyl group (Δφov) depends on the nature of the onium group.
The effect of the photodecomposition of chlorpromazine on lecithin monolayers
Authors: Nejmeh Maha , Pilpel N 
Published: April 2011

Abstract
Chlorpromazine hydrochloride (cpz) is decomposed when irradiated with ultraviolet light, forming H+, hydrochloric acid, chlorpromazine sulphoxide and 2-hydroxypromazine. The order of the reaction (as measured by the expansion that is produced in a lecithin/cpz monolayer) varies between zero and about 3/4. The results have been used to explain some of the adverse side effects that are observed when patients are treated with cpz.
Gastric ulceration and the concentration of salicylate in plasma in rats after administration of 14C-labelled aspirin and its synthetic triglyceride, 1,3-dipalmitoyl-2(2′-acetoxy-[14C]carboxylbenzoyl) glycerol
Authors: Kumar R , Billimoria J D 
Published: April 2011

Abstract
Triglycerides containing aspirin in place of one or more fatty acid residues of the molecule have been synthesized. Metabolism of the compound with the labelled (14C) drug residue introduced specifically into the 2-position of the triglyceride is reported. Plasma salicylate concentrations with this synthetic glyceride were determined and compared with those obtained with commercially available aspirin labelled with the 14C-isotope. Both compounds gave a therapeutic concentration of salicylate in the plasma after ingestion. The 1,3-di-fatty acyl-2-aspirin glyceride was absorbed through the intestine as 2-aspirin monoglyceride, some 20% of which was transported through the thoracic-duct chyle and about 30% through the portal system. Whereas pronounced ulceration of the rat stomach occurred with free aspirin, the above fatty acyl glyceride of aspirin produced no ulceration.
Assessment of the neuroleptic potential of some novel benzamide, butyrophenone, phenothiazine and indole derivatives
Authors: Costall B , Funderburk W H , Leonard C A , Naylor R J 
Published: April 2011

Abstract
A series of experimental models were used to determine the activity spectra of potential neuroleptic agents on extrapyramidal and/or mesolimbic dopamine systems: catalepsy induction by the drug alone or in the presence of the acetylcholine-like agent, RS86 [spiro-(N'-methylpiperidyl-4′)-N-ethyl succinamide hydrogen fumarate], or α-methyl-p-tyrosine (α-MT), stereotypy antagonism (amphetamine) and hyperactivity antagonism (intra-accumbens and intrastriatal dopamine). Antiemetic potential was also considered. Whilst classical neuroleptics were active in all test situations, other neuroleptics including benzamide, phenothiazine, butyrophenone and indole derivatives exhibited novel activity spectra: clozapine failed to interact with α-MT, metoclopramide failed to antagonize a mesolimbic hyperactivity or interact with the acetylcholine-like agent. Other benzamide derivatives, clebopride, AHR6092, sultopride and tiapride also failed to interact with RS86, but whilst clebopride was active in all other test situations, AHR6092 was inactive in all but the antiemetic test, sultopride was only weakly cataleptogenic and tiapride only antagonized stereotypy and hyperactivity from the striatum. AHR6839, AHR6134, AHR6645, AHR6505B and AHR1709 were generally inactive in the catalepsy tests but exerted dopamine antagonistic potential in other test procedures. The antagonistic ability of AHR1709 was only revealed in the tests where dopamine function was specifically raised in the nucleus accumbens and caudate-putamen by intracerebral dopamine injections. Data are discussed in terms of a dissociation of drug effects on different cerebral dopamine systems.
The release of a model low-dose drug (riboflavine) from hard gelatin capsule formulations
Authors: Stewart A G , Grant D J W , Newton J M 
Published: April 2011

Abstract
The in vitro release of a model low dose drug, riboflavine, from hard gelatin capsules, formulated with a range of diluents, in the absence and presence of magnesium stearate (0.5, 1.0 and 2.0% w/w), has been assessed by a dissolution technique. Comparison of the values of the time for 50% of the drug content of the capsule to appear in solution T50, by analysis of variance, indicated that the type of diluent significantly influenced the drug release. Irrespective of the magnesium stearate content, the diluents could be ranked in the following order of effectiveness: Primojel &gt; sodium bicarbonate &gt; Avicel ≃ Dri-flo starch ≃ lactose &gt; Emcompress ≃ kaolin &gt; starch. Correction of the T50 values for possible adsorption of riboflavine onto the water insoluble diluents, using experimentally determined adsorption isotherms, altered the relative order of effectiveness of the diluents to Primojel &gt; sodium bicarbonate &gt; kaolin ≃ lactose &gt; Avicel ≃ Dri-flo starch &gt; Emcompress &gt; starch. Comparison of the urinary excretion of riboflavine, after administration of capsule formulations containing lactose, Emcompress or kaolin as the diluent, to volunteers, suggests that the dissolution results not corrected for adsorption provide a better indication of the in vivo performance of the formulations.
A method to estimate binding constants at variable protein concentrations
Authors: Romer Jurg , Bickel Marcel H 
Published: April 2011

Abstract
The association constants of the binding of chlorpromazine and imipramine to serum albumin at low saturation of the protein were determined by a new experimental approach with the protein concentration rather than the ligand concentration being varied. This approach is suitable for estimating binding constants in systems with one class of binding sites. In addition, the method is proposed to complement conventional binding studies of systems with two classes of binding constant with higher accuracy.
An in vitro method simulating drug release from viscous eye drops in rabbit and man
Authors: Melis-Decerf C , van Ooteghem M 
Published: April 2011

Abstract
A method has been developed using a diffusion cell in an attempt to determine the drug release from viscous solutions under conditions simulating the blinking movements in the rabbit and human eye. Diffusion coefficients were determined at rest and at different velocities. For the solutions at rest, corresponding with the conditions at the surface of the rabbit cornea, the diffusion velocity decreases with increasing viscosity. When the solution is moved at a velocity corresponding to that of lachrymal fluid at the surface of the human eye, the influence of viscosity may be neglected.
A comparison of the cardiovascular effects of centrally administered clonidine and adrenaline in the anaesthetized rat
Authors: Borkowski Kazimierz R , Finch Lionel 
Published: April 2011

Abstract
Intracerebroventricular (i.c.v.) injections of clonidine and adrenaline-induced hypotension and bradycardia in urethane anaesthetized spontaneous hypertensive rats. The hypotension induced by clonidine (3 μg i.c.v.) was antagonized by pretreatment with the α-antagonists piperoxan, which also antagonized clonidine-induced bradycardia, and yohimbine. The hypotension and bradycardia induced by adrenaline (10 μg i.c.v.) were unaffected by α-antagonist pretreatment, while β-antagonist pretreatment with (-(-propranolol or metoprolol was effective against adrenaline but not clonidine-induced hypotension and bradycardia. Pretreatments with the histamine H2-receptor antagonists metiamide and cimetidine antagonized clonidine but not adrenaline-induced hypotension. These data indicate that different central mechanisms are involved in mediating the hypotension and bradycardia induced by centrally administered clonidine and adrenaline and do not, therefore, support the hypothesis that the hypotensive effects of clonidine (i.c.v.) are mediated by central adrenaline receptor activation in urethane-anaesthetized spontaneous hypertensive rats.
Long-lasting inhibition of angiotensin response in rats by depot administration of octanoyl-[Leu8]-angiotensin II
Authors: Abdulkader Regina C , Silva Helio B , Marcondes Marcello , Vasconcelos Eleonidas A , Paiva Antonio C M 
Published: April 2011

Abstract
Depot administration of a lipophilic angiotensin II (AII) antagonist was tested for obtaining prolonged inhibition of the pressor response to AII in rats. Intramuscular injections of 1.5 or 5.0 mg of octanoyl-[Leu8]AII (oct-LAII), in oil solution produced the same degree of AII inhibition either 6 h or 24 h after the injection. The inhibition was comparable to that expected from the continuous intravenous infusion of oct-LAII at the rate of 1.2 μg kg−1 min−1. The prolonged effect of intramuscular injections of oct-LAII in oil solution may be useful for chronic studies of physiopathological states involving the renin-angiotensin-aldosterone system.
Plasma corticosterone responses to stress following chronic oral administration of diazepam in the rat
Authors: Barlow S M , Knight A F , Sullivan F M 
Published: April 2011

Abstract
The effect of daily, oral administration of diazepam on plasma corticosterone responses to stressors of varying intensity was investigated. In rats exposed to the mild stress of noise, diazepam, 10 mg kg−1 but not 1.0 or 0.1 mg kg−1, reduced plasma corticosterone concentrations by 30% in comparison with controls. However, in rats exposed to the more severe stressors, foot-shock or immobilization, none of these doses of diazepam reduced plasma corticosterone responses. In unstressed rats, diazepam 10 mg kg−1 raised plasma corticosterone concentrations. It is suggested that plasma corticosterone concentrations are not a reliable indicator of the tranquillizing effect of diazepam during stress.
p-Chloroamphetamine-induced hyperthermia pharmacologically distinct from fenfluramine-induced hyperthermia
Authors: Quock Raymond M , Weick Barton G 
Published: April 2011

Abstract
The influence of various drug pretreatments upon the responses of rabbits to the putative indirect 5-hydroxytryptamincrgic agonists p-chloroamphetamine (PCA) and fenfluramine were examined. In naive rabbits PCA evoked hyperthermia, behavioural excitation and prominent forepaw clonic activity, while fenfluramine produced only hyperthermia and behavioural stimulation. The hyperthermic and behavioural responses of both agents were reduced by the 5-hydroxytryptamine (5-HT) uptake inhibitor, fluoxetine, potentiated by the monoamine oxidase inhibitor, pheniprazine, and unaltered by the dopaminergic antagonist, haloperidol. Pretreatment with the 5-hydroxytryptaminergic receptor blockers cinanserin, cyproheptadine or D-2-bromolysergic acid diethylamide markedly attenuated the effects of fenfluramine but only slightly influenced the responses to PCA. Depeletion of central 5-HT stores with p-chlorophenylalanine also affected responses to fenfluramine more than responses to PCA. The tryptaminergic receptor blocker methergoline abolished both PCA-induced hyperthermia and forepaw clonus-but not behavioural stimulation—while the effects of fenfluramine were only partly reduced. We interpret these data to mean that PCA- and fenfluramine-induced drug effects have different underlying mechanisms, the PCA responses relying possibly upon tryptamine while the fenfluramine responses are 5-hydroxytryptaminergic.
The application of cryobiology to the microbiological assay of nystatin
Authors: Cosgrove R F , Beezer A E , Miles R J 
Published: April 2011

Abstract
Improvements in the reproducibility of nystatin agar diffusion assays have been achieved by the use of liquid nitrogen stored inocula and deep frozen standard stock solutions. The overall percentage variability of the assay has been reduced from over 5% with daily prepared standards and inocula to around 1% with a frozen inocula and to 0.6% with a combination of frozen inocula and standards. The implications of these improvements in the standardization of nystatin assays, and microbiological assays generally are discussed.
Modification of cortical neuron responses to acetylcholine by viloxazine
Authors: Jones R S G , Roberts M H T 
Published: April 2011

Abstract
Viloxazine, an antidepressant with no peripheral antiacetylcholine activity, was capable of reducing responses of single cortical neurons to acetylcholine. Acetylcholine responses could also be potentiated by viloxazine. Both potentiation and reduction by viloxazine were often seen in the same study, reduction of responses invariably preceding potentiation. These results suggest that viloxazine may have selective effects on central cholinergic receptors. Responses of cortical neurons to monoamines could also be potentiated by viloxazine although it has little effect on monoamine uptake. These results are compatible with the idea that potentiation of monoamine responses may occur by a postsynaptic mechanism.
N-o-Methoxyphenylpiperazine: a simple blocker of dopaminergic receptors in the brain
Authors: Minard Frederick N , Cain John C , Grant Dennis S , Dren Anthony T 
Published: April 2011

Abstract
N-o-Methoxyphenylpiperazine (MPP) is a moderately effective in vivo blocker of dopaminergic receptors. Its ability to increase the concentration of rat brain homovanillic acid (HVA) and the resulting time course for HVA were similar to the actions of clozapine. The increased concentration of HVA did not result from decreased outflow from brain because HVA also rapidly decreased after a subsequent injection of pargyline. MPP blocked the circling behaviour caused by apomorphine in mice with a unilateral striatal lesion, and MPP and apomorphine reciprocally blocked the occurrence of stereotypy and increased HVA in rats. Diazepam partially prevented the MPP-induced elevation of HVA. Thus, both biochemical and pharmacological evidence indicate the dopaminergic blocking action of MPP.
Percutaneous absorption: in vivo experiments
Authors: Albery W John , Hadgraft Jonathan 
Published: April 2011

Abstract
The percutaneous absorption of esters of nicotinic acid has been studied in vivo in man. The time for erythema to be produced has been measured both when the ester is applied continuously and in ‘pulse’ experiments when the ester is removed before the erythema develops. The results show that the erythema is produced long before steady state diffusion across the epidermis is established and the penetration of methyl nicotinate is characterized by D/l2 = 2.3 × 10−4 s−1 where D is the diffusion coefficient and l the thickness of the barrier. Results using glycerol water mixtures in the external phase show that the route of penetration for methyl nicotinate is through the interstitial channels and not through the keratinized cells. Data for absorption from various creams and ointments (Barrett et al 1964) show that the route is independent of the nature of the external phase. Steady state data for the absorption of salicylic acid and carbinoxamine through the abdominal skin of guinea-pigs (Arita et al 1970) show that the route of penetration does not change as the experiment proceeds. Data for the absorption of other substances (Michaels et al 1975) also fit the interstitial route.
Kidney function and lithium concentrations of rats given an injection of lithium orotate or lithium carbonate
Authors: Smith Donald F , Schou Mogens 
Published: April 2011

Abstract
A recent study by Kling et al (1978) noted the finding of higher lithium concentrations in serum and brain of rats after an intraperitoneal injection (2 mmol lithium kg−1) of lithium orotate as a slurry than of lithium carbonate in solution. The authors suggested that lithium orotate might offer advantages in the treatment of patients. We repeated the experiments of Kling et al but in addition examined the kidney function of the rats. Glomerular filtration rate and urine flow were markedly lower in rats given lithium orotate than in rats given lithium carbonate, sodium chloride or a sham injection. The renal lithium clearance was significantly lower, the kidney weight and the lithium concentrations in serum, kidney and heart significantly higher after injection of lithium orotate than after injection of lithium carbonate. The higher lithium concentrations could be accounted for by the lower kidney function. It seems inadvisable to use lithium orotate for the treatment of patients.
Pentobarbitone and skeletal muscle contractions: on the interaction with the effect elicited by the β-adrenoceptor agonist, terbutaline
Authors: Holmberg Eva , Waldeck Bertil 
Published: April 2011

Abstract
The soleus, a slow-contracting muscle, and the extensor digitorum longus (EDL), a fast-contracting muscle from guinea-pig were prepared for isometric recording in vitro. Sub-tetanic contractions were evoked by transmural field-stimulation. Pentobarbitone increased the force of contraction in both muscles. In the soleus it shifted the stimulation frequency-response curve to the left. Terbutaline caused a decrease in the force of subtetanic contractions of the soleus, an effect which was dependent on the stimulation frequency. In the presence of pentobarbitone, the stimulation frequency had to be lowered by about 2 Hz in order to maintain the optimum response to terbutaline. The EDL responded to terbutaline with an increased force of contraction. In this case the stimulation frequency was less critical and the effects were the same in the presence and in the absence of pentobarbitone. Experiments with α-chloralose yielded results similar to those obtained with pentobarbitone.
A comparative study of the microbiological assays currently available for nystatin raw material
Authors: Cosgrove R F , Beezer A E , Miles R J 
Published: April 2011

Abstract
The classical agar diffusion and turbidimetric methods of assay for nystatin are compared with the more recently documented assays for this antibiotic which depend upon physicochemical measurement of the response of micro-organisms. Liquid nitrogen stored inocula were used throughout. It is concluded that the newer methods of assay are as reproducible and reliable as the agar diffusion and turbidimetric methods and that they are generally more sensitive. The choice between the assay methods compared can thus be based on speed, cost and sample through-put.
Relationships between poloxamer structure and the solubilization of some para-substituted acetanilides
Authors: Collett J H , Tobin Elizabeth A 
Published: April 2011

Abstract
Saturation solubilities of several para-substituted acetanilides have been measured at 37 °C in aqueous solutions of structurally related polyoxyethylene-polyoxypropylene block copolymers-poloxamers L62, L63, L64, P65 and F68. These poloxamers differ only in the amount of ethylene oxide in the hydrophil. Solubilities increased with increasing poloxamer concentration. As the oxyethylene chain length of the poloxamer increased, then the solubilizing capacity per equivalent of oxyethylene decreased. The moles of acetanilide derivative solubilized per mole of poloxamer increased with poloxamer oxyethylene content in the case of the less hydrophobic acetanilides but was invariant in the more hydrophobic ones. The solubilizing capacities have been discussed in terms of the inter-relationships between the hydrophobic nature of the solubilizate and solubilizer and the site of solubilization on the poloxamer molecule.
The effect of simultaneous administration of 3,4-dihydroxyphenylpyruvic acid and L-dopa on the bioavailability of L-dopa in rat and mouse
Authors: Hietala P , Lindén Inge-Britt , Gronfors Nina 
Published: April 2011

Abstract
In the rat, administration of 3-(3,4-dihydroxy)-l-phenylalanine (l-dopa) simultaneously with the corresponding α-keto acid, 3,4-dihydroxyphenylpyruvic acid (DHPPA), gives significantly higher concentrations of l-dopa in the serum and of dopamine and homovanillic acid in the brain than the same dose of l-dopa alone. Correspondingly, DHPPA potentiates the effect of l-dopa on the locomotor activity in reserpine-treated mice. DHPPA is postulated to increase the absorption of intact l-dopa from the gut by preventing the transamination reaction between l-dopa and the physiological α-keto acids.
Powder mixing in direct compression formulation by ordered and random processes
Authors: Johnson M C R 
Published: April 2011

Abstract
The mixing processes taking place in a two component system involving a cohesive drug, tetracycline and a direct compression vehicle, spray dried lactose (SDL), have been studied by chemical analysis of powder samples and fluorescence microscopy. At a drug concentration level of 0.25% w/w, both random and ordered mixing is taking place. Mixture quality is better (Cv = 1 %) using a fine grade of crystalline lactose (CL) than with SDL (Cv = 4%). Using fractionated material, it was found that SDL between 106 and 300 μm gave Cv values up to 12%, whereas with SDL below 106 μm values of 2% were obtained. The poor quality of the SDL mixtures is attributed to ordered unit segregation.
Uptake of 5-hydroxytryptamine in blood platelets and its inhibition by drugs: role of plasma membrane and granular storage
Authors: Laubscher Andreas , Pletscher Alfred 
Published: April 2011

Abstract
The initial uptake of 3H-5-hydroxytryptamine (3H-5-HT) showed linearity for short time intervals in normal and reserpinized blood platelets of guinea-pigs, but was lower in reserpinized platelets. The Km values for the 3H-5-HT uptake were virtually identical in normal and reserpinized platelets, whereas Vmax was lower in the latter. Imipramine and chlorpromazine caused the same percentage inhibition of 3H-5-HT uptake in normal and reserpinized platelets; the reserpine-like compound Ro 4–1284 inhibited the uptake of 3H-5-HT in the normal, but not markedly in the reserpinized platelets. Haloperidol, prenylamine and Ro 4–9040 were more potent inhibitors in normal than in reserpinized platelets. It is concluded that (a) the Km of the initial uptake of 5-HT by platelets is probably determined by the mechanism at the plasma membrane, whereas Vmax may be codetermined by the intracellular storage capacity, (b) platelets are models for differentiating the site of action (plasma membrane or storage organelles) of drugs interfering with 5-HT uptake, and (c) neuroleptics- and reserpine-like compounds may either act selectively on the plasma membrane or on the intracellular storage organelles, or affect both of these subcellular sites.