bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological Properties of β-Amyrin Palmitate, a Novel Centrally Acting Compound, Isolated from Lobelia inflata Leaves
Authors: Subarnas Anas , Tadano Takeshi , Oshima Yoshiteru , Kisara Kensuke , Ohizumi Yasushi 
Published: April 2011

Abstract
Effects of β-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, β-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg−1). β-Amyrin palmitate (5, 10 and 20 mg kg−1) or mianserin (5, 10 and 20 mg kg−1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg−1) increased locomotor activity and potentiated methamphet-amine-induced hyperactivity. β-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg−1) and imipramine (10 and 20 mg kg−1) antagonized the reserpine-induced effect. Unlike imipramine, β-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. β-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg−1) decreased it in a dose-dependent manner. A potentiating effect of β-amyrin palmitate (5, 10 and 20 mg kg−1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg−1) but weaker than that of mianserin (2·5, 5 and 10 mg kg−1). These results suggest that β-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action. We suggest that β-amyrin palmitate has antidepressant activity with a mianserin-like profile of action.
Prediction of Cathodal Iontophoretic Transport of Various Anions Across Excised Skin from Different Vehicles Using Conductivity Measurements
Authors: Yoshida Nagahiro H , Roberts Michael S 
Published: April 2011

Abstract
Solute concentration, buffer concentration, applied pH and buffer constituents affect the cathodal iontophoresis of salicylate, benzoate and butyrate across excised skin. Experiments were conducted in which the iontophoretic flux of salicylate was measured across excised human skin with variations in salicylate concentration, donor solution pH, buffer concentrations and buffer consitutents. The conductivity of these solutes and of solutions described in studies on the iontophoresis of benzoate and butyrate were then measured.
The observed variations in salicylate, benzoate and butyrate fluxes across a range of conditions were found to be related to the ratio of specific conductance of the solutes in deionized distilled water to that in the buffer solution containing the solutes.
The present results suggest that conductivity of solutes in vehicle solutions is one means of predicting the iontophoretic flux of solutes from different vehicle compositions.
Comparative Evaluation of Butea frondosa and Flurbiprofen for Ocular Anti-inflammatory Activity in Rabbits
Authors: Mengi S A , Deshpande S G 
Published: April 2011

Abstract
The roots and leaves of the plant Butea frondosa were evaluated for ocular anti-inflammatory activity on the subacute model of ocular inflammation in rabbits.
The arkas (liquid preparations obtained by distillation of certain liquids or drugs soaked in water, using the Arka-Yantra or any other convenient modern distillation apparatus) were prepared using the roots and leaves of the plant. The arkas were formulated as gels using Pluronic F-127 (PF-127) 30% w/w as the polymer. The anti-inflammatory activity of the preparations were assessed by determining their effects on elevated intraocular pressure consequent to breakdown of blood/aqueous humour barrier. A commercial eyedrop of flurbiprofen 0.03% w/w was used to compare the ocular anti-inflammatory activity of the arkas of the plant. A marketed root arka was included in the study for comparison. The anti-inflammatory activity of the arkas formulated as gels were compared with flurbiprofen gel prepared using the same polymer. The changes in intraocular pressure were monitored at various time intervals after a single dose administration of the aqueous as well as gel formulations. In multiple dose studies the aqueous preparations were administered three times a day, while the gels were administered once a day up to day 30 and the intraocular pressure was monitored on different days post-administration.
The findings reveal statistically significant differences (P &lt; 0.05) between the arkas of the plant and the commercial eyedrop of flurbiprofen. The arkas of the plant proved to be better than the eyedrop of flurbiprofen, while with respect to gels, the intraocular pressure monitored at various time intervals revealed no statistically significant difference (P &gt; 0.05) between the gel formulations. However, the changes in intraocular pressure monitored on different days post-administration until day 30, demonstrated that the gel produced from B. frondosa leaves arka was superior to all the other gels with respect to the extent of reduction of elevated intraocular pressure elicited experimentally.
The Effects of Opioid Peptides on Cardiovascular Function and Sympathetic Neurotransmission in Rats
Authors: Mcintosh M A , Kane K A , Parratt J R 
Published: April 2011

Abstract
The haemodynamic effects of three opioid receptor agonists, with some preferential activity on δ-, μ- and κ-receptors were investigated in anaesthetized and pithed rats, and effects on sympathetic neurotransmission were also investigated in pithed rats.
In anaesthetized rats, d-Ala2-d-Leu5-enkephalin (DADLE) (a predominantly δ-receptor agonist, 10 μg kg−1), glyol (μ, 0·5 mg kg−1) and R,S-N-C2-N-methyl-3,4,dichloro-phenylacetamido-2-C3-carboxy phenylethyl-pyrrolidine (ICI 204448) (·, 0·1 mg kg−1) by intravenous administration transiently decreased heart rate from 462 ± 12 to 432 ± 14, 460 ± 12 to 448 ± 13 and 460 ± 12 to 448 ± 11 beats min−1, respectively, and mean arterial blood pressure from 142 ± 6 to 111 ± 9, 141 ± 6 to 122 ± 5 and 148 ± 7 to 121 ± 6 mmHg, respectively. The effects of DADLE, but not those of glyol or ICI 204448, were blocked by M8008, a δ-receptor antagonist. In pithed rats, none of the opioid agonists had any significant effects on heart rate or mean arterial blood pressure; however, acetylcholine significantly reduced both heart rate and mean arterial blood pressure. All three opioid agonists reduced the positive chronotropic response to thoracic (C7-T2) spinal cord stimulation in pithed rats, by 17 ± 4,30 ± 2 and 20 ± 10% for DADLE, glyol and ICI 204448, respectively. This compared with a 48 ± 15% reduction with clonidine (5 μ kg−1). This effect of DADLE was almost abolished by M8008.
It is concluded that the haemodynamic effects of the opioid agonists studied are mediated via actions on the central nervous system and that a decrease in sympathetic neurotransmission may account for, at least in part, the bradycardia produced by opioid agonists in intact anaesthetized rats. It seems that the sympathetic nervous system is unlikely to be involved in the arrhythmogenic effects of opioid peptides.
Effects of Cimetidine, Ranitidine and Omeprazole on Tolbutamide Pharmacokinetics
Authors: Toon S , Holt B L , Mullins F G P , Khan A 
Published: April 2011

Abstract
This randomized, four-way crossover study in 16 healthy subjects compared the effects of cimetidine 800 mg, ranitidine 300 mg and omeprazole 40 mg against placebo given daily after breakfast for seven days on the pharmacokinetics of a single oral dose of tolbutamide (500 mg) given on day 4.
Plasma tolbutamide and urinary hydroxytolbutamide and carboxytolbutamide concentrations were determined by HPLC. Ranitidine had no significant effects on tolbutamide metabolism. Cimetidine produced a 20% increase in AUC (P &lt; 0·001) and a 14% increase in t 1/2 (P &lt; 0·01), while omeprazole produced a 10% increase in AUC (P &lt; 001). The effect of these agents on urinary concentrations of the tolbutamide metabolites was small.
These results do not indicate that interactions of major clinical significance occur in healthy subjects.
Effect of Policosanol on Lipofundin-induced Atherosclerotic Lesions in Rats
Authors: Noa M , Más R , De La Rosa M C , Magraner J 
Published: April 2011

Abstract
Policosanol is a mixture of higher aliphatic alcohols isolated from sugar cane wax, showing cholesterol-lowering effects and preventing the development of lipofundin-induced lesions in New Zealand rabbits. This study was conducted to determine whether policosanol orally administered to rats also protects against the development of lipofundin-induced atherosclerotic lesions.
Fifty four male Wistar rats were randomly distributed amongst a negative control group, a positive control group intravenously injected with lipofundin for eight days, and four experimental groups also injected with lipofundin, but orally receiving policosanol at 0·5, 2·5, 5 and 25 mg kg−1, respectively. Policosanol treatment was orally administered once-a-day for eight days, while control groups similarly received equivalent amounts of vehicle. A significant reduction of the atherosclerotic lesions in the treated animals was observed.
It is concluded that policosanol has a protective effect on lipofundin-induced aortic lesions in Wistar rats.
The Transhepatic Response to Noradrenaline in the Rabbit Liver: the Influence of Arterioportal Pressure Gradient
Authors: Browse Dominic J , Benjamin Irving S , Alexander Barry 
Published: April 2011

Abstract
The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10−10−10−4mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline.
At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68·5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged.
These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance.
Irreversible Inhibition of Rat Liver Mitochondrial MAO A and MAO B by Enantiomers of Deprenyl and α-Methylpargyline
Authors: Robinson J B , Bocchinfuso R , Khalil Amira 
Published: April 2011

Abstract
Using rat liver mitochondrial monoamine oxidase (MAO) A and MAO B, the possible influence of stereochemical factors upon the irreversible inhibition by propargylamine derivatives has been studied using the enantiomers of deprenyl and of α-methylpargyline.
Whether studying the inhibition of MAO A or MAO B, little difference was found among enantiomeric pairs in the first-order rate constant (k2) for formation of the enzyme inhibitor adduct. Similarly, and with the exception of (S)-d-(+)-deprenyl (k2 = 0 or an extremely low value at MAO A), the computed value of k2 for the individual enantiomers showed little variation between MAO A and MAO B.
These results suggest that inhibitor selectivity towards a particular form of the enzyme is determined predominantly at the competitive phase of the inhibition.
In-vitro and In-vivo Studies of the Diclofenac Sodium Controlled-release Matrix Tablets
Authors: Liu Cheng-Hsiung , Kao Yuh-Horng , Chen Shou-Chiung , Sokoloski Theodore D , Sheu Ming-Thau 
Published: April 2011

Abstract
Controlled release matrix tablets for diclofenac sodium were developed in this study.
Five matrix-tablet formulations were prepared by granulating two viscosity grades of HPMC (hydroxylpropylmethylcellulose) in varying ratios with water in the planetary mixer. The in-vitro dissolution tests indicate that all five matrix formulations prolong the release of diclofenac sodium. The main factors controlling drug release were the HPMC viscosity grade and the amount of HPMC used. The larger the amount of high viscosity grade HPMC used, the slower the resultant release rate of diclofenac sodium. There was no significant degradation of diclofenac sodium or change in drug release rate in any of the five formulations during a three-month period of stability testing. The sustained release ability of four formulations was further demonstrated in an in-vivo study in six healthy subjects.
There were in-vitro/in-vivo correlations between Cmax, AUC0–14, and the time for 50 or 80% drug to be released.
Spectroscopic Analysis of the Binding of Amylobarbitone, Secbutobarbitone, Pentobarbitone, Phenobarbitone and Quinalbarbitone to Human Serum Albumin
Authors: González-Jimènez J , Moreno F , Blanco F Garcìa 
Published: April 2011

Abstract
The binding of five barbiturates: amylobarbitone, secbutobarbitone, pentobarbitone, phenobarbitone and quinalbarbitone to human serum albumin (HSA) was studied by difference spectroscopy and spectro-fluorimetric titrations. There were no changes in the HSA spectral properties. Our result suggest that there are two classes of binding sites on HSA for these barbiturates. A detailed investigation of the effect of their binding to HSA by deconvoluted spectra, suggests that the interaction of barbiturate-HSA takes place principally on the subdomain IIIA of HSA.
Lack of an Effect of Madopar on the Disposition of Tolcapone and its 3-O-Methylated Metabolite in Rats
Authors: Funaki Tomoo , Onodera Hideko , Ushiyama Naomi , Tsukamoto Yuko , Tagami Chieko , Fukazawa Hideo , Kuruma Isami 
Published: April 2011

Abstract
The effect of Madopar (benserazide and l-dopa, 1:4) on the disposition of the new selective inhibitor of catechol-O-methyltransferase, tolcapone, in rats was investigated. There was no statistically significant difference in the pharmacokinetic parameters of tolcapone in the presence or absence of Madopar except for a change in the mean residence time after oral administration. Thus, we rejected the hypothesis that the consumption of S-adenyl-l-methionine by Madopar would change the disposition of tolcapone.
There were no statistically significant differences in the cumulative amount absorbed of drug and the absorption rate in the presence or absence of Madopar. We concluded that there was no interaction between tolcapone and Madopar.
Bioavailability and Pharmacokinetics of Sublingual Oxytocin in Male Volunteers
Authors: de Groot Akosua N J A , Vree Tom B , Hekster Yechiel A , Pesman Gerard J , Sweep Fred C G J , van Dongen Pieter J W , van Roosmalen Jos 
Published: April 2011

Abstract
The aim of this investigation was to assess the bioavailability and pharmacokinetics of oxytocin in six male subjects after a sublingual dose of 400 int. units (684 μg) and after an intravenous dose of 1 int. unit (1·71 μg).
After intravenous administration, the pharmacokinetic profile could be described with a two-compartment model. The distribution half-life was 0·049 ± 0·016 h, the elimination half-life was 0·33 ± 0·23 h, the total body clearance was 67·1 ± 13·4 Lh−1 and the volume of distribution was 33·2 ± 28·1 L. After sublingual administration, a poor bioavailability with a 10-fold variation between 0·007 and 0·07% was observed. The pharmacokinetic profile could be described with a one-compartment model. The lag time was subject-dependent and ranged between 0·12 and 0·30 h (40% CV). The absorption half-life was 0·45 ± 0·29 h, and the apparent elimination half-life 0·69 ± 0·26 h.
This study showed a very poor and interindividual variability in bioavailability. The sublingual route of administration with its ‘long’ lag time and ‘long’ absorption half-life would not seem a reliable route for accurate high dosing for immediate prevention of post-partum haemorrhage.
Synthesis and Antiplatelet Effects of ω-Aminoalkoxylxanthones
Authors: Lin Chun-Nan , Liou Shorong-Shii , Lai Shih-Chen , Lin Hsien-Cheng , Ko Feng-Nien , Liu Hong-Wen , Teng Che-Ming 
Published: April 2011

Abstract
A series of ω-aminoalkoxylxanthones were synthesized and tested in-vitro for their ability to inhibit aggregation of rabbit washed platelets and human platelet-rich plasma (PRP) induced by various inducers. Nine of these compounds showed more potent antiplatelet effects than natural norathyriol tetraacetate on collagen-induced aggregation. The various ω-aminoalkoxyl side chains of the synthesized compounds modified the antiplatelet effects. All the compounds tested in human PRP showed significant inhibition of secondary aggregation induced by adrenaline, suggesting that the antiplatelet effects of these compounds is mainly due to an inhibitory effect on thromboxane formation. These compounds at high concentration also cause vasorelaxing action in rat thoracic aorta.
Inotropic and Chronotropic Effects of 4-(4′-n-Butylaniline)-7,8-dimethoxy-5H-pyrimido[5,4–b]indole in Guinea-pig Atria
Authors: Castiella E , Frechilla D , Lasheras B , Cenarruzabeitia E , Martínez De Irujo J J , Alberdi E , Santiago E , Monge A , Villanueva A , Martinez F J , Font M 
Published: April 2011

Abstract
Cardiotonic effect of 4-(4′-n-butylaniline)-7,8-dimethoxy-5H-pyrimido[5,4-b)]indole (B11) was investigated in isolated cardiac tissue preparations. The action of this agent on force of contraction, beating frequency and cyclic nucleotide phosphodiesterase (PDE) activity was studied. Amrinone was used for comparison.
B11 produced concentration-dependent (5 × 10−6-1 × 10−4m) positive inotropic and positive chronotropic responses in guinea-pig atrial tissues. The potency of B11 was greater than that of amrinone. The cardiotonic effects of B11 were not modified by β-adrenoceptor blockade. Carbachol inhibited the positive inotropic effect of B11. The activity of B11 was increased in desensitized left atrial tissues. B11 inhibited the activities of PDE isoenzymes (type I, II, IV and V) from dog heart ventricle and PDE type IV from guinea-pig heart ventricle nonselectively.
It is concluded that B11 possesses potent positive inotropic activity in guinea-pig atria, and the effect is probably mediated by a non-selective inhibition of PDE activity.
QSAR Studies of Some Sulphonamidobenzophenone Oximes with Antiviral Activity
Authors: Hadjipavlou-Litina Dimitra J 
Published: April 2011

Abstract
A study of quantitative structure-activity relationships (QSAR) has been performed for some sulphonamidobenzophenone oximes to investigate the mechanism of their antiviral activity against polio and rhino viruses.
It has been shown that viral macromolecule synthesis could be the target of their action and that the antiviral activity of the compounds is predominantly controlled by steric factors.
Preservative Efficacy Tests in Formulated Nasal Products: Reproducibility and Factors Affecting Preservative Activity
Authors: Hodges N A , Denyer S P , Hanlon G W , Reynolds J P 
Published: April 2011

Abstract
Preservative efficacy tests were performed in triplicate on each of three batches of three formulated nasal spray preparations to assess the inter- and intra-batch variation in preservative performance which typically results from these procedures, and to assess the relative importance of factors influencing preservative performance in nasal products.
Tests were conducted using procedures conforming, as far as possible, to both the European and the US pharmacopoeias and the results interpreted using the performance criteria of both. Despite the adoption of practices designed to maximize reproducibility, a marked variation in the degree of microbial inactivation was observed, both within and between batches of product.
A preservative system comprising benzalkonium chloride and phenylethyl alcohol was found to be far superior to combinations of either benzalkonium chloride plus disodium edetate or potassium sorbate plus disodium edetate, both of which failed to satisfy the EP performance criteria on a number of occasions. Proposals are made for the adoption of inactivation criteria which incorporate realistic error limits reflecting the inherent problems of reproducibility of the viable counting procedures involved.
Immunopharmacological Activity of the Purified Insoluble Glucan, Zymocel, in Mice
Authors: Suzuki Tatsuya , Ohno Naohito , Chiba Norihisa , Miura Noriko N , Adachi Yoshiyuki , Yadomae Toshiro 
Published: April 2011

Abstract
Although it has been established that soluble glucan in fungi is important to host defence against infection, the importance of insoluble glucans is not clear. We have examined the in-vivo immunopharmacological activity of the insoluble glucan, zymocel.
Administration of zymocel increased peritoneal exudate cell number and spleen weight, and enhanced: phagocytic activity, hydrogen peroxide production, and nitric oxide production of peritoneal exudate cells; the extravascular release of Evans blue (which might reflect vascular permeability); lipopolysaccharide-triggered synthesis of tumour necrosis factor (TNF); and recovery of white blood cell number in cyclophosphamide-induced leukopenia. Zymocel also showed anti-tumour activity against sarcoma 180 in mice and also enhanced TNF synthesis and hydrogen peroxide production by macrophage-like cell line in-vitro, i.e. resulted in direct macrophage activation.
These results show that zymocel shows varied immunopharmacological activity; it is suggested that the administration of insoluble glucan induces the inflammatory response, the subsequent activation of the immune systems via the cytokine network, and direct macrophage activation.
CR 2249: a New Putative Memory Enhancer. Behavioural Studies on Learning and Memory in Rats and Mice
Authors: Garofalo Paolo , Colombo Silvia , Lanza Marco , Revel Laura , Makovec Francesco 
Published: April 2011

Abstract
The effects of S-4-amino-5-[4,4-dimethylcyclohexyl)amino]-5-oxopentanoic acid (CR 2249), a new entity selected from a new series of glutamic acid derivatives, has been investigated in different paradigms for screening nootropics.
CR 2249 ameliorated the memory retention deficit produced by scopolamine in step-through-type passive avoidance in rats and by electroconvulsive shock in step-down-type passive avoidance in mice. CR 2249 was also capable of improving performance in behavioural tests of learning and memory in the absence of cholinergic hypofunction or cognitive deficit. The activity was determined using different passive and active avoidance behavioural test procedures on rats. CR 2249 was active only when given 45 min before training and did not show any effect when administered immediately after the learning training or before the retention trial. No changes in the general behaviour or motor activity of the animals were observed, indicating that CR 2249 effects cannot be attributed to sensory-motor deficit. Microdialysis experiments have shown that CR 2249 significantly increased noradrenaline release in the hippocampus of freely moving rats and reduced 3,4-dihydroxyphenylglycol efflux. These effects have led us to hypothesize that CR 2249 memory effect might be mediated by a direct or indirect action on noradrenergic transmission. These behavioural results suggest that this new agent has clinical application in memory disorders.