bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ha-117 and Ha-118 are potent dopamine receptor agonists
Authors: Ilhan Mustafa , Long John P , Cannon Joseph G 
Published: April 2011

Abstract
In-vitro studies evaluated the presynaptic dopamine receptor activities of trans-N-propyl-7,9-dihydroxyoctahydrobenzo[f]quinoline (Ha-117) and trans-N-ethyl-7,9-dihydroxyoctahydrobenzo[f]quinoline (Ha-118) using isolated field-stimulated cat right atria. Ha-117 and Ha-118 were found to be potent dopamine receptor agonists since their effects were antagonized by haloperidol. Compounds were inactive on presynaptic α2-adrenoceptors using rat vas deferens and guinea-pig ileum. Results show that both resorcinol derivatives of octahydrobenzo[f]quinoline are potent dopamine receptor agonists without having presynaptic α2-adrenoceptor stimulating activity.
Microencapsulation of paracetamol using polyacrylate resins (Eudragit Retard), kinetics of drug release and evaluation of kinetic model
Authors: Benita Shimon , Hoffman Amnon , Donbrow Max 
Published: April 2011

Abstract
Methacrylate copolymers were used for microencapsulation of paracetamol by phase separation from chloroform with polyisobutylene 6% in cyclohexane. With polyisobutylene as an anti-aggregating agent, high quality microcapsules were obtained. Drug release appeared to fit both first order and Higuchi matrix model kinetics. However, on application of the differential rate treatment, the evidence supported the first order description, which was further supported by computed simulations of the models. Variation of production conditions showed that increasing the proportion of core material raised the microcapsule drug content and the release rate. Reduction of core particle size correlated with reduced coating thickness and faster release rate. The rate constants correlated with the estimated surface areas and wall thicknesses of the various batches. The data were used to estimate an apparent permeability constant for paracetamol in Eudragit RS microcapsules, which was constant and comparable with values found single core, non-aggregated microcapsules containing other similar drugs and different wall materials.
Nicotine binding to brain tissue from drug-naive and nicotine-treated rats
Authors: Benwell M E M , Balfour D J K 
Published: April 2011

Abstract
Two nicotine binding sites with dissociation constants for nicotine of approximately 3 nM and 12 μM respectively have been found in homogenates of rat hippocampus, hypothalamus, parietal cortex and mesencephalon, the greatest density of high affinity binding sites being in parietal cortex (30.0 ± 3.0 fmol (mg protein)−1), the lowest in hypothalamus (16.1 ± 1.0 fmol (mg protein)−1). The density of the low affinity sites (approx. 20 pmol (mg protein)−1) did not show any regional variation. Neither site was present in homogenates of medulla oblongata. The accumulation of radioactivity following the subcutaneous administration of [3H]nicotine (0.4 mg kg−1) was rapid, the highest concentrations being found in the brain regions with the highest density of high affinity binding sites. Medulla oblongata did not accumulate radioactivity above the concentration found in plasma. The chronic administration of nicotine (0.4 mg kg−1 s.c. daily for 39 days) had no significant effects on [3H]nicotine binding to brain tissue or its accumulation into brain following subcutaneous administration. It is concluded that nicotine readily passes from plasma into brain tissue and is accumulated in the areas containing high affinity binding sites for the compound. It is also concluded that the biochemical and behavioural effects reported previously in response to the chronic daily administration of nicotine do not depend upon changes in its uptake or binding by brain tissue.
α-Adrenergic agonist and antagonist activity of dihydroergotoxine in rats
Authors: Roquebert Jacques , Demichel Patricia 
Published: April 2011

Abstract
The α-adrenergic activity of dihydroergotoxine had been studied in both pithed and urethane or pentobarbitone anaesthetized rats. In anaesthetized rats, blood pressure effects varied with the anaesthetic agent: hypotension with urethane, hypertension with pentobarbitone. This latter pressor response was a peripheral effect. In pithed rats, the vasopressor response to dihydroergotoxine was reduced competitively by yohimbine, and noncompetitively by nifedipine, but not by prazosin or methysergide, showing that the vasoconstriction is mediated by α2-adrenoceptors. Dihydroergotoxine decreases the tachycardia elicited by stimulation of the cardioaccelerator nerves, this effect being antagonized by yohimbine. It also reduced the pressor response to (-)-phenylephrine. These results indicated that, on the peripheral vascular system of the rat, dihydroergotoxine acts as an α1-adrenoceptor blocker and an α2-adrenoceptor agonist.
Cerebrospinal fluid uptake and peripheral distribution of centrally acting drugs: Relation to lipid solubility
Authors: Ochs Hermann R , Greenblatt David J , Abernethy Darrell R , Arendt Rainer M , Gerloff Joachim , Eichelkraut Wolfgang , Hahn Norbert 
Published: April 2011

Abstract
In an anaesthetized dog model, serum kinetics and CSF entry were determined after i.v. administration of the following 8 drugs: salicylic acid (as acetylsalicylic acid), antipyrine, acetaminophen (paracetamol), lidocaine (lignocaine), trimipramine, amitriptyline, haloperidol, and imipramine. Kinetic variables were evaluated in relation to in-vitro lipophilicity, measured by the reverse-phase high-pressure liquid chromatographic (HPLC) retention index. After correction for individual values of serum binding (determined as the CSF: serum ratio at equilibrium), in-vivo volume of distribution was highly correlated with HPLC retention (r = 0.92). Conversely, the time of peak CSF concentration and the CSF entry half-life were negatively correlated with HPLC retention (r = −0.83 and −0.63, respectively). Thus lipophilicity is a physiochemical property which has an influence on the peripheral distribution of drugs as well as their rate of entry into CSF.
Evidence against VIP or substance P being the transmitter in non-cholinergic excitatory nerves supplying the guinea-pig bladder
Authors: Meldrum Lorna A , Burnstock Geoffrey 
Published: April 2011

Abstract
In the guinea-pig bladder, contractile responses to substance P (0.3 μM) and VIP (3 μM) were unaffected by P2-purinoceptor desensitization with α,β-methylene ATP (3 times 10−6M), while the responses to stimulation of the non-cholinergic excitatory nerves (4–16 Hz) were abolished. The evidence presented suggests that ATP or a related purine nucleotide, and not VIP or substance P, is responsible for the non-cholinergic excitatory component of the nerve-mediated response.
Dose-dependent effect of calcium and magnesium etidronate on salicylic acid absorption in the rat
Authors: Shrewsbury Robert P , Wurster Dale Eric , Dittert Lewis W 
Published: April 2011

Abstract
Disodium etidronate affected salicylic acid absorption from the rat small intestine, in-situ, when instilled into a jejunal segment for different exposure times before the salicylic acid absorption was measured. At low etidronate concentrations and short exposure times, the salicylic acid absorption rate was significantly increased compared with saline controls. At high etidronate concentrations and longer exposure times, the absorption rate was reduced. Etidronate precomplexed with calcium or magnesium ions at low concentrations still enhanced salicylic acid absorption but at high concentrations absorption of salicylic acid was close to saline controls. Intestinal mucosa exposed to high etidronate concentrations showed a progressive structural destruction but with the complexes, there was no visible alteration. It is proposed that a solubilized etidronate complex, formed either in-situ or administered as such, is responsible for enhancing salicylic acid absorption. This effect is hidden at high etidronate concentrations because of the deterioration of the mucosal surface and at high complex concentrations because these decrease the absorbing surface area and increase the viscosity of the lumen contents.
Stress crack resistance of some pigmented and unpigmented tablet film coating systems
Authors: Okhamafe Augustine O , York P 
Published: April 2011

Abstract
Stress crack resistance parameters—tensile strength: Young's modulus ratio, relative surface energy, and toughness index—have been examined for unpigmented free films of hydroxypropyl methylcellulose containing polyvinyl alcohol, and polyethylene glycols 400 and 1000, as well as similar film systems pigmented with either talc or titanium dioxide. Incorporation of either polyvinyl alcohol or polyethylene glycols 400 and 1000 in hydroxypropyl methylcellulose film coatings eliminated the incidence of edge splitting in the coated tablets. Increase in pigment concentration generally led to a decrease in the crack resistance of pigmented films. There was a relation between the stress crack resistance of pigmented free films and the incidence of edge splitting of corresponding film coatings applied to aspirin tablets—generally, the higher the crack resistance the lower the incidence of edge splitting. A similar relationship applied to the unpigmented films only when the tensile strength: Young's modulus ratio was considered.
Extension of Johnson's equation of homogeneity of random mixtures
Authors: Egermann H 
Published: April 2011

Abstract
The volume-weighted/volume-number mean particle diameter of the ingredient is applied to the equation of Johnson (1972) as a measure of the mean particle size defining the degree of homogeneity of random mixtures. By introducing the volume shape factor, the applications of this equation are extended to ingredients of nonspherical particle shape.
Similarities in the release rates of different drugs from polyethylene glycol 6000 solid dispersions
Authors: Dubois Jean-Luc , Ford James L 
Published: April 2011

Abstract
The dissolution rates (mg min−1) of 10 drugs, solid dispersed by fusion in polyethylene glycol 6000 (PEG 6000) have been examined by rotating disc methodology. The dispersions generally displayed release rates which were linearly dependent upon the drug concentration (% drug) at high polymer content. However the range over which this linearity was encountered varied unduly, e.g. 0–2% for phenylbutazone and 0–15% for paracetamol. The slope of this line (mean value: 0.451 mg min−1 %−1) was statistically the same for nine of the drugs studied, the exception being griseofulvin which did not form a true solid dispersion but was a microcrystatline dispersion of the drug within the PEG. During fusion, chain scission of the PEG 6000 occurred in the presence of several drugs. PEG 6000 was incompatible with disulfiram, frusemide, chlorothiazide and chlorpropamide.
Intracisternal glycine activates the micturition reflex in urethane-anaesthetized rats
Authors: Maggi Alberto Carlo , Furio Martino , Santicioli Paolo , Meli Alberto 
Published: April 2011

Abstract
Intracisternal glycine, but not GABA, activates a series of neurogenic rhythmic contractions of the urinary bladder in urethane-anaesthetized rats. This effect of glycine was prevented by strychnine but not by bicuculline, indicating the involvement of specific glycinergic receptors. The effects of glycine were also prevented by either atropine or haloperidol suggesting an involvement of cholinergic and monoaminergic excitatory neurotransmission to the bladder.
The fate of pharmaceutical chemicals in the aquatic environment
Authors: Richardson Mervyn L , Bowron Judith M 
Published: April 2011

Abstract
Increased demands for potable water, especially where supplies are drawn from lowland rivers has necessitated a greater degree of water re-use. As water undertakings have a duty to maintain the wholesome quality of potable water supplies, increasing concern is being expressed over the presence of organic micro-contaminants (contaminants found at μg litre−1 concentrations). This study outlines some of the problems encountered in assessing the risk from pharmaceutical chemicals which might enter the water cycle from domestic and industrial sources. Analytical chemistry was of value for only a few of the 200 compounds studied. However, much useful information was derived from the human metabolic routes of the drugs and is collated in Appendix I. Biodegradation studies and other ecotoxicity/environmental toxicology data may be required to a greater extent in the future. Particular consideration is given to vulnerable sections of the population.
A photometric analysis of tablet movement in a side-vented perforated drum (Accela-Cota)
Authors: Leaver T M , Shannon H D , Rowe R C 
Published: April 2011

Abstract
A novel particle tracing technique has been used to study the effect of the normal process variables i.e. drum speed, drum loading and the presence/absence of mixing elements (baffles) on the movement of tablets in a side-vented perforated drum (24 in diameter Accela-Cota). The technique involves measuring the duration of light emission from a single luminous tablet using a photomultiplier mounted to scan the same area as a spray gun, and has enabled the quantification of both the time that the tablet spends on the surface per pass (surface time) and the time that the tablet spends within the bulk of the tablet bed (circulation time) over run lengths equating to the normal tablet coating cycle. The technique also allows the study of the uniformity of tablet appearances by means of circulation profiles. It was found that, while both the surface and circulation times decreased with increasing drum speed and loading, there was irregularity of tablet appearance especially at low drum speeds and in the absence of baffles.
Displacement of striatal 5-hydroxytryptamine by dopamine released from endogenous stores
Authors: Waldmeier P C 
Published: April 2011

Abstract
Combined treatment with amfonelic acid and neuroleptics caused a considerable loss of striatal, but not cortical 5-hydroxytryptamine (5-HT) in rats. This could be prevented by pretreatment with the specific 5-HT uptake inhibitor, citalopram. The results are best explained by the assumption that the combined treatment with amfonelic acid and neuroleptic had massively released dopamine into the synaptic cleft, and a part of this had been taken up into the 5-HT neurons by the 5-HT uptake mechanism and displaced the indoleamine.
Muscarinic cholinergic receptors in rabbit retina
Authors: Neal M J , Dawson C 
Published: April 2011

Abstract
Binding sites with high affinity and specificity for [3 H]-quinuclidinyl benzilate are present in rabbit retinal homogenates. Only one set of binding sites was detected with an apparent dissociation constant of 2.13 times 10−10 M and a density of 59.2 fmol mg−1 of protein. The pharmacological characteristics of specific binding were similar to those in the goldfish, chicken and cow.
Comparative evaluation of the effects of lidocaine (lignocaine) hydrochloride and salicylate on nervous and purkinje fibres
Authors: Mitolo-Chieppa D , Carratù M R , Dubois J M , Mugelli A , Amerini S , Conte-Camerino D , Siro-Brigiani G 
Published: April 2011

Abstract
Lidocaine hydrochloride and lidocaine salicylate (lisacaine) have been tested on the frog node of Ranvier, on the sheep cardiac Purkinje fibres and rat phrenic nerve-diaphragm. On the node of Ranvier both drugs produced the same degree of reduction of peak INa and steady-state potassium current and the same degree of shift of the steady-state inactivation curve for INa to more negative potential. Lisacaine took less time to reach the steady-state effect. On the cardiac Purkinje fibres both drugs decreased the action potential duration without any detectable difference; but their effects on V max (i.e. the maximum rate of depolarization) were different, that of lisacaine being faster. On the rat phrenic nerve-diaphragm both drugs produced the same percentage of reduction of the contractile response of diaphragm but, the action of lisacaine was faster. Therefore the lidocaine molecule with the salicylate anion while displaying the same anaesthetic effectiveness has a faster action than the hydrochloride.
The preparation and properties of niosomes—non-ionic surfactant vesicles
Authors: Baillie A J , Florence A T , Hume L R , Muirhead G T , Rogerson A 
Published: April 2011

Abstract
Vesicles were prepared on hydration of a mixture of a single or double alkyl-chain, non-ionic surfactant with cholesterol. These vesicles, or ‘niosomes’, are capable of entrapping and retaining water soluble solutes such as carboxyfluorescein, are osmotically active and can be formulated to release entrapped solute slowly. The physical characteristics of the vesicles were found to be dependent on the method of production and three such methods, based on liposome technology, are described. The vesicles have been characterized by photon correlation spectroscopy, freeze fracture electron micrography, measurement of solute entrapment efficiency, and solute release rates. Vesicular forms of the single chain surfactant which could be formed under certain conditions in the absence of cholesterol are also described.
Evidence for dopamine release and metabolism beyond the control of nerve impulses and dopamine receptors in rat substantia nigra
Authors: Nissbrandt H , Pileblad E , Carlsson A 
Published: April 2011

Abstract
In rat substantia nigra a biphasic disappearance curve of dopamine (DA) was seen after tyrosine hydroxylase inhibition by α-methyl-p-tyrosine (α-MT): the initial phase had a fast turnover and a half life of 0&#x006d;̇5 h and the later phase had an extremely slow turnover. In contrast to the effects in striatum, neither haloperidol nor apomorphine influenced α-MT-induced DA disappearance in the substantia nigra. Furthermore, inhibition of impulse flow by γ-butyrolactone prevented DA disappearance in striatum but not in the substantia nigra. Measurements of DA and 3-methoxytyramine following treatment with inhibitors of monoamine oxidase (pargyline) and catechol-O-methyl transferase (tropolone) indicated that O-methylation is a more important metabolic pathway in the substantia nigra than in the striatum. The data are interpreted to indicate that the release and metabolism of DA in the substantia nigra are largely beyond the control of nerve impulses and DA receptors. It is suggested that such an arrangement forms an important feature of autoreceptor-mediated feedback control of DA nerve cell activity.
The effect of the relationship between punch velocity and particle size on the compaction behaviour of materials with varying deformation mechanisms
Authors: Roberts R J , Rowe R C 
Published: April 2011

Abstract
The effect of punch velocity over the range 0.033–300 mm s−1 on the compaction properties of lactose, microcrystalline cellulose and a drug substance (a phthalazine derivative) for a range of particle sizes has been studied using the yield pressure derived from the Heckel relationship and a strain rate sensitivity index (SRS index), as the criteria to describe their behaviour. For lactose, a material which deforms by a mixed mechanism of particle fracture and plastic deformation at the contact points, the yield pressure increased and the SRS index decreased as particle size decreased, due to a reduction in the amount of fragmentation of the particles. For microcrystalline cellulose, a material which is known to deform plastically, the yield pressure and the SRS index were independent of particle size. For the phthalazine derivative the yield pressure increased as particle size decreased; however the SRS index reduced from 41% to zero, indicating that the deformation mechanism was changing from plastic flow to brittle behaviour. This decrease in the SRS index has been explained in terms of the relative amounts of strain-hardened material produced as milling severity increased, resulting in an increasing resistance to deformation and thus an apparent increase in brittle behaviour as particle size decreased.
Comparison of fluorescence polarization immunoassay and high performance liquid chromatography for the quantitative determination of phenytoin, phenobarbitone and carbamazepine in serum
Authors: Ashy Abdul Rahman , El-Sayed Yousry M , Islam Samira I 
Published: April 2011

Abstract
The Abbott TDx fluorescence polarization immunoassay (FPIA) system has been evaluated and compared with well-established high performance liquid chromatography (HPLC) for the determination of three anticonvulsant drugs: phenytoin, phenobarbitone and carbamazepine. These assays were evaluated for precision, calibration curve stability, specificity and accuracy. Within-run precision studies using control samples (n = 15) in the subtherapeutic, therapeutic, and toxic concentrations, resulted in coefficients of variation in the range of 1.79–3.99% (FPIA) and 1.16–2.52% (HPLC), respectively. Between-run precision ranged from 2.32–6.34% for FPIA and from 2.04–3.38% for HPLC. Comparison of 122 patient samples assayed with both methods indicated an extremely good analytical correlation (r = 0.96) for all three comparisons. The FPIA method offers significant advantages in calibration curve stability while maintaining accuracy and precision comparable with those of established HPLC procedures.
Dual effect of orally administered sennosides on large intestine transit and fluid absorption in the rat
Authors: Leng-Peschlow Elke 
Published: April 2011

Abstract
Quantity and consistency of the faecal output, large intestine transit time, and colonic net fluid absorption were investigated in rats after oral administration of sennosides A + B (12.5–200 mg kg−1). The release of normal faecal pellets was accelerated 3–4 h after drug administration; excretion of soft faeces was evident within 4–5 h and reached its maximum 5–7 h after administration. Large intestine transit time was dose- and time-dependently influenced by sennoside treatment. A highly significant reduction in transit time from more than 6 h in controls to 90 min for a 2 h pretreatment and a nearly maximal reduction to 30 min for a 4 h pretreatment was induced by a dose of 50 mg kg−1. Inhibition of net fluid absorption in the colon was maximal with the same dose, but clearly more pronounced after a 6 h pretreatment period than after a 4 h period. Since the increase in fluid volume due to net fluid secretion is delayed compared with the acceleration of large intestine transit, the early motility effect seems to be largely independent of the changes in absorption mechanisms. Therefore, the laxative effect of the sennosides consists of changes in colon motility as well as in colonic fluid absorption, but motility may be an earlier and more sensitive parameter than net absorption.
Neither morphine nor clonidine influence the non-adrenergic, non-cholinergic inhibitory response in the rat gastric fundus
Authors: Lefebvre R A , Bogaert M G 
Published: April 2011

Abstract
Morphine and clonidine are among the few agents reported to modulate non-adrenergic, non-cholinergic (NANC) responses in different tissues. They were therefore tested for their effect on the NANC inhibitory response in the rat gastric fundus. Neither morphine (10−5 M), nor clonidine (10−5 M in the presence of prazosin 10−6 M to avoid its own relaxatory effect) modified the NANC response in the rat gastric fundus.
Differing potencies of muscle relaxants on rat and guinea-pig phrenic nerve diaphragm preparations
Authors: Bradshaw E G , Harper N J N , Pleuvry B J , Modla C Y 
Published: April 2011

Abstract
The sensitivities of two in-vitro preparations to neuromuscular blocking agents have been compared. The guinea-pig phrenic nerve diaphragm preparation proved to be more sensitive to vecuronium, atracurium and pancuronium than the equivalent preparation from the rat. Only tubocurarine had a similar potency on the preparations from both species. This would suggest that the guinea-pig diaphragm would be the most appropriate bioassay preparation if only small quantities of drug were available. Small differences in the cholinesterase content of the preparations was not thought to be a likely reason for the differences between the two preparations.