bluuebunny/crossref_metadata_2025_split huggingface dataset:
Partition of Dopamine Antagonists into Synthetic Lipid Bilayers: the Effect of Membrane Structure and Composition
Authors: Sarmento Ana Bela , De Lima M C Pedroso , Olivejra C R 
Published: April 2011

Abstract
Partition coefficients, Kp, of four dopamine antagonists (pimozide, fluspirilene, haloperidol and domperidone) between the aqueous phase and lipid bilayer vesicles were determined as a function of lipid chain length, unsaturation and temperature encompassing the range of the lipid phase transition. Model membranes of egg phosphatidylcholine (PC), dimyristoyl (DMPC)-, dipalmitoyl (DPPC)-, distearoyl (DSPC)- and dioleoyl (DOPC)-phosphatidylcholines were studied. Kp values of the drugs are different in the various membranes under study and depend on temperature, aliphatic carbon chain-length and on the presence of unsaturation in the aliphatic lipid chain. First-order transition of membrane lipids from the gel to the liquid crystalline state is accompanied by a sharp increase of the partition coefficient of pimozide and fluspirilene in DMPC, DPPC and DSPC bilayers. For domperidone, Kp values are maximal within the midpoint of phase transition of DMPC and DPPC, while for DSPC Kp values increase progressively with increasing temperature. Haloperidol Kp values display a maximum at the mid-point of phase transition of DMPC, while a progressive increase of Kp is observed in DPPC and DSPC. The four drugs are easily accommodated in bilayers of short aliphatic chain lipids (DMPC), the partition coefficients being 17137 for pimozide, 18 700 for fluspirilene, 686 for domperidone and 722 for haloperidol, at temperatures 10°C below the mid-point of the lipid phase transition. Except for haloperidol, the partition of the drugs in DOPC (18:1) is higher than that in DSPC (18:0) bilayers at a temperature above the phase transition temperature of both lipids. From our experiments we can conclude that artificial membranes are useful models to understand the physicochemical mechanisms involved in the interaction of dopamine antagonists with biological membranes.
Effect of Local Anaesthetics on the Stimulus-secretion Coupling in Bovine Adrenal Chromaffin Cells
Authors: Kawabata Kazunaga , Sumikawa Koji , Kamibayashi Takahiko , Fukumitsu Kazuo , Hayashi Yukio , Takada Koji , Yoshiya Ikuto 
Published: April 2011

Abstract
This study was carried out to determine the relative potencies of local anaesthetics to inhibit the cholinergic synaptic transmission using cultured bovine adrenal chromaffin cells, and to clarify if the inhibitory action would correlate with biophysical and pharmacological properties. Local anaesthetics (bupivacaine, etidocaine, tetracaine, lignocaine and procaine; 0·02–2 Mm) inhibited carbachol-induced catecholamine release from the cells in a concentration-dependent manner. This inhibition was completely reversible. IC50 (concentration of 50% inhibition) of each anaesthetic showed no correlation with the lipid solubility. The local anaesthetics showed greater inhibitory potency at a higher extracellular pH. The results suggest that clinically relevant concentrations of local anaesthetics inhibit the stimulus-secretion coupling in the chromaffin cells. The un-ionized base form plays a major role, and the inhibitory potency does not depend on the lipid solubility of the anaesthetics.
Buprenorphine-cocaine Interactions in Mice: Effect on Locomotor Activity and Hole-dipping Behaviour
Authors: Jackson Helen C , Griffin Ian J , Nutt David J 
Published: April 2011

Abstract
The effect of cocaine and the mixed μ-opioid partial agonist/κ-antagonist buprenorphine on locomotor activity and hole-dipping behaviour was investigated in mice. The drugs were given alone and in combination. Cocaine (7·5, 15, 30 mg kg−1, i.p.) significantly increased locomotion in a dose-related manner in the hour following injection. The two highest doses also increased hole-dipping although this response was not consistently seen. Buprenorphine (0·5, 5 mg kg−1, i.p.) produced an increase in locomotion which occurred 30–60 min after injection but did not alter hole-dipping behaviour. A lower dose (0·05 mg kg−1) had no effect on either parameter. The locomotion induced by cocaine (15 mg kg−1, i.p.) was not modified by buprenorphine (0·05, 0·5, 1, 5 mg kg−1, i.p.; 5 min pretreatment). However, hole-dipping was almost completely abolished in animals given combinations of cocaine and buprenorphine (0·05–5 mg kg−1, i.p.), although neither drug decreased hole-dipping when given alone. This observation, which was not simply due to the emergence of stereotyped behaviour, suggests an interaction between buprenorphine and cocaine.
Adenosine Stimulates Human Sperm Motility via A2 Receptors
Authors: Shen Meng-Ru , Linden Joel , Chiang Po-Hui , Chen Shun-Sheng , Wu Sheng-Nan 
Published: April 2011

Abstract
The effects of adenosine and its analogues on human sperm motility were studied using a transmembrane migration method. Specific binding sites for adenosine in human sperm were also investigated. Adenosine and 5′-N-ethylcarboxamidoadenosine (NECA) stimulated human sperm motility with similar efficacies and the maximal amplitudes of motility increases were both about 70%. 3,7-Dimethyl-1-propargylxanthine (DMPX), a potent A2 antagonist, competitively antagonized NECA-induced motility stimulation. Successively higher concentrations of DMPX shifted the dose-response curve of NECA to the right in a nearly parallel fashion. Dipyridamole, an inhibitor of adenosine uptake, does not reduce the ability of adenosine to stimulate human sperm motility. In radioligand-binding studies, adenosine A1 selective analogues, cyclopentyl-1,3-dipropylxanthine and 1-methyl-2-phenylethyl adenosine, have little competitive effect on [3H]NECA binding in human sperm membrane. These results provide evidence that adenosine enhances human sperm motility via adenosine A2 receptors on the surface of sperm membranes.
The Effects of Antibiotics and Steroids on the Carriage of Vaginal Bacteria into the Uterus During Insertion of Intra-uterine Monofilaments in the Guinea-pig
Authors: Malhi Jaspal S , Gard Paul R , Hanlon Geoffrey W 
Published: April 2011

Abstract
The effects of systemic norethisterone acetate and oxytetracycline hydrochloride on the levels of vaginal microorganisms found in the uterus after the insertion of transcervical, intra-uterine monofilaments in the guinea-pig were determined. The results indicated that bacteria were transferred to the uterus from the vagina during the insertion process and, in the presence of an intra-uterine substrate, persisted for up to 6 months. Daily treatment with norethisterone acetate or oxytetracycline hydrochloride whilst the monofilament was in-situ failed to reduce the bacterial numbers in the uterus. Similarly, daily treatment with oxytetracycline hydrochloride for the 5 days before monofilament insertion had no effect on these bacteria.
Elucidation of the structural requirements for the bioactivation of mianserin in-vitro
Authors: Roberts P , Kitteringham N R , Park B K 
Published: April 2011

Abstract
The aim of this study was to investigate structure-activity relationships among a series of compounds related to the antidepressant drug, mianserin, with respect to their ability to produce cytotoxic metabolites. Human peripheral lymphocytes were used as target cells and these were exposed to the individual compounds, in the presence or absence of a drug metabolizing system derived from human liver. The individual enantiomers of mianserin showed differences in their cytotoxicity profiles; the R-(–) isomer giving NADPH-dependent cytotoxicity while the S-(+) isomer showed direct cytotoxicity at high concentrations. Cytotoxicity was reduced by removal from mianserin of the nitrogen atom at the 5 position and by substitution of a methyl group for a hydrogen atom at position 14b. In contrast, insertion of an oxygen atom at position 10 of the drug molecule, precluding the formation of a carbonium ion, had little effect on cytotoxic metabolite formation. The data are consistent with the proposal that one or more iminium ions derived from mianserin are responsible for the cytotoxicity observed in this in-vitro system and that appropriate chemical modification may preclude bioactivation of mianserin by P450 enzymes.
Stabilization of thymopentin and preservation of its pharmacological properties by 2-hydroxypropyl-β-cyclodextrin
Authors: Brown Nesbitt D , Butler Dennis L , Chiang Peter K 
Published: April 2011

Abstract
Thymopentin prepared in 5, 15, and 20% 2-hydroxypropyl-β-cyclodextrin (HPCD) was able to inhibit guinea-pig ileum contraction stimulated by anatoxin-a (3 × 10−6 m) after fourteen months of storage at room temperature. Thus, in contrast to the instability of thymopentin prepared without HPCD, the pharmacological activity was retained and could be stored in a ready-to-use solution for extended periods without refrigeration.
Opioid pathways exert a tonic restraint in the guinea-pig isolated colon: changes after chronic sympathetic denervation
Authors: Marino Franca , Creta Filomena , De Ponti Fabrizio , Giaroni Cristina , Lecchini Sergio , Frigo Gian Mario 
Published: April 2011

Abstract
We have studied the effects of naloxone on acetylcholine and noradrenaline release in the guinea-pig isolated distal colon, and have assessed the effect of naloxone on electrically-induced contractions of the longitudinal muscle and non-adrenergic, non-cholinergic (NANC) relaxations of the circular muscle coat. Naloxone dose-dependently increased resting and electrically-evoked acetylcholine release and electrically-evoked noradrenaline release. Naloxone was more potent in increasing resting acetylcholine release in colonic specimens obtained after chronic sympathetic denervation. Naloxone (1 μm) did not affect electrically-induced contractions of the longitudinal muscle, while it enhanced NANC relaxations of the circular muscle. The effects observed with naloxone in the present experiments suggest that opioid pathways exert a tonic restraint on neurotransmission in the guinea-pig colon. After suppression of the adrenergic inhibitory tone, the functional relevance of opioid pathways seems to be increased.
Sequential changes of [3H]cyclic AMP binding in the gerbil brain following transient cerebral ischaemia
Authors: Araki Tsutomu , Kato Hiroyuki , Kanai Yasuo , Kogure Kyuya 
Published: April 2011

Abstract
Sequential alterations in the binding of [3H]cyclic AMP (cAMP) as an indicator of cAMP-dependent protein kinase (cAMP-DPK) binding activity following transient cerebral ischaemia were studied in the gerbil brain using receptor autoradiography. Transient ischaemia was induced for 10 min. [3H]cAMP binding in the stratum oriens and pyramidale of the hippocampal CA1 sector significantly decreased in the early post-ischaemic stage and showed severe reduction 7 days and 1 month after recirculation. By contrast, [3H]cAMP binding showed no significant alterations in the stratum radiatum of the hippocampal CA1 sector and the stratum pyramidale of the hippocampal CA3 sector up to 48 h after ischaemia. However, the binding in these areas significantly decreased 7 days and 1 month after ischaemia. The stratum lacunosum-moleculare of the hippocampal CA1 sector and dentate gyrus showed no significant changes in [3H]cAMP binding throughout the recirculation period. However, in the dorsolateral part of the striatum, where severe neuronal damage was seen morphologically, [3H]cAMP binding was significantly reduced only one month after ischaemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 sector, but not in the striatum. Furthermore, our autoradiographic data suggest that post-ischaemic alteration in [3H]cAMP binding between the hippocampal CA1 sector and striatum may be produced by different mechanisms.
Drug Dissolution from Indomethacin-starch Hybrid Powders Prepared by the Dry Impact Blending Method
Authors: Ishizaka Takafumi , Honda Hirotaka , Koishi Masumi 
Published: April 2011

Abstract
Indomethacin was hybridized with potato starch using a dry impact blending method. Resultant hybrid powders were investigated by scanning electron microscopy and X-ray powder diffraction. Amorphous indomethacin spread over the starch surface in a layer immediately after being hybridized, and then gradually reverted to fine crystalline particles adhering firmly to the starch surface. Indomethacin dissolution from the hybrid powder was compared with those from physical mixtures and granules taken from a commercially available capsule. Indomethacin dissolution from powder and capsule dosage forms, even in an acidic medium, was drastically accelerated by the hybridization.
Further Evaluation of a New Penetration Enhancer, HPE-101
Authors: Yano Tadanori , Higo Naruhito , Fukuda Kazuya , Tsuji Masayoshi , Noda Kanji , Otagiri Masaki 
Published: April 2011

Abstract
The penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), significantly enhanced the excretion of topically applied [14C]indomethacin when dissolved in dipropylene glycol, triethylene glycol, diethylene glycol, 1,3-butylene glycol, trimethylene glycol, glycerin, water, silicone or triethanolamine, but not when dissolved in ethanol, isopropyl alcohol, oleyl alcohol, olive oil, peppermint oil, isopropyl myristate or hexylene glycol. HPE-101 significantly enhanced the excretion of [14C]indomethacin, [14C]nicotinic acid, [14C]5-fluorouracil, [3H]oestradiol and [3H]triamcinolone acetonide, but not that of [3H]testosterone. HPE-101 also significantly enhanced the excretion of [14C]indomethacin applied to intact skin of rabbit, guinea-pig and rat, and to tape-stripped skin of guinea-pig, but did not enhance the excretion of [14C]indomethacin applied to tape-stripped skin of rat or rabbit.
Further Studies on α2-Adrenoceptor Subtypes Involved in the Modulation of [3H]Noradrenaline and [3H]5-Hydroxytryptamine Release from Rat Brain Cortex Synaptosomes
Authors: Gobbi M , Frittoli E , Mennini T 
Published: April 2011

Abstract
Three selective α2A- or α2B-adrenergic antagonists (BRL-44408, BRL-41992 and imiloxan) were cused in the present study designed to classify the presynaptic α2-auto- and heteroreceptors in the rat brain cortex. The rank order of potency in antagonizing the inhibitory effect of (–)-noradrenaline or clonidine on the K+-induced [3H]noradrenaline and [3H]5-hydroxytryptamine (5-HT) release from superfused synaptosomes was BRL-44408 ≥ BRL-41992»imiloxan. The same rank order was found for the affinities of these compounds for [3H]yohimbine binding in human platelet membranes, containing only α2A-adrenoceptors, but does not correlate with the known affinities for α2B-adrenoceptors (BRL-41992 ≥ imiloxan &gt; BRL-44408). These data support the conclusion that presynaptic α2-auto- and heteroreceptors in rat brain cortex do not belong to the α2B-subtype and suggest that the modulation of noradrenaline and 5-HT release may be mediated by the α2A-subtype.
Pharmacokinetics of Chlorimipramine, Chlorpromazine and their N-Dealkylated Metabolites in Plasma of Healthy Volunteers After a Single Oral Dose of the Parent Compounds
Authors: Corte L Della , Valoti M , Palmi M , Giovannini M G , Sgaragli G P 
Published: April 2011

Abstract
A single oral dose of 0·7 mg kg−1 clorimipramine (n= 18) and chlorpromazine (n= 16) was given to each subject 45 days apart and plasma concentrations of parent drugs and their monodesmethyl and didesmethyl metabolites were measured by GC. Ingestion of chlorimipramine resulted in an area under the plasma concentration-time curve (AUC 0–24) for parent drug plus metabolites 5-fold higher than that observed in the same subjects following chlorpromazine intake (600 ± 87 and 124 ± 14 ng mL−1, respectively). Plasma chlorimipramine levels reached a mean peak value of 43·8 ng mL−1, an average of 3·4 h after dosage, whereas the mean peak chlorpromazine level was 15·1 ng mL−1, which occurred 2 h after administration. Desmethyl metabolite kinetics of chlorimipramine appeared to be elimination rate-limited and those of chlorpromazine appeared to be formation-rate-limited. The response to single doses of these two drugs in healthy subjects highlights the two distinct dispositional processes involved, thus offering pharmacokinetic explanation of the hitherto empirical discrepancy in dosage levels in chronic treatment.
Pharmacokinetic and Pharmacodynamic Aspects of Artelinic Acid in Rodents
Authors: Titulaer H A C , Eling W M C , Zuidema J 
Published: April 2011

Abstract
The efficacy of artelinic acid and artemisinin, orally administered at 10 and 50 mg kg−1 day−1, was compared in Plasmodium berghei infected mice. Subsequently, the pharmacokinetics of artelinic acid after intravenous, intramuscular, oral and rectal administration of a 20 mg kg−1 aqueous solution to rabbits were studied in a four-way randomized cross-over experiment. After intravenous administration, artelinic acid concentrations in blood plasma were high (C0: 76 ± 15 mg L−1), and the drug was rapidly eliminated from the central compartment, showing linear elimination kinetics with an elimination half-life of 15 ± 3 min. A large inter-subject variation appeared in the absorption rate and the extent of absorption (2–92%) over the 120 min interval after intramuscular administration. Also, a large inter-subject variation in individual rectal bioavailability (17–100%) was shown, which was dependent on the site of absorption in the rectum. The estimated oral bioavailability was low (4·6 ± 1·7%), probably due to a high first-pass effect and possible decomposition in the acidic gastric environment.
Stereoselective Interaction of Mianserin with 5-HT3 Receptors
Authors: Wood M D , Thomas D R , Watkins C J , Newberry N R 
Published: April 2011

Abstract
The interaction of the enantiomers of mianserin with the 5-HT3 receptor was determined. Using [3H]granisetron binding, (–)-mianserin was more potent than (+)-mianserin (pKi 8·46 and 6·95, respectively). The enantiomers competitively antagonized the depolarizing effect of 5-hydroxytryptamine in the rat vagus nerve preparation (pKapp: (–)-mianserin 8·13, (+)-mianserin 6·58). This stereoselectivity was maintained in-vivo as determined using ex-vivo inhibition of [3H]granisetron binding. Therefore, in contrast to its enantiomeric selectivity for the 5-HT1C and 5-HT2 receptors, where the (+)-isomer is more potent, the enantiomeric selectivity of mianserin for the 5-HT3 receptor was reversed. This differential selectivity of the enantiomers of mianserin may be useful in elucidating its utility in anxiety states.
Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro
Authors: Takeyama Kiyoshi , Tamaoki Jun , Chiyotani Atsushi , Tagaya Etsuko , Konno Kimio 
Published: April 2011

Abstract
We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin &gt; erythromycin » clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.
Extracellular 5-hydroxytryptamine concentration in rat hypothalamus after administration of fluoxetine plus l-5-hydroxytryptophan
Authors: Perry Kenneth W , Fuller Ray W 
Published: April 2011

Abstract
Fluoxetine (10 mg kg−1, i.p.) caused a three- to fourfold increase in extracellular 5-hydroxytryptamine (5-HT) concentration measured by microdialysis in hypothalamus of freely moving rats. The addition of l-5-hydroxytryptophan at 20 or 40 mg kg−1, i.p. doses, magnified the increase in extracellular 5-HT to as much as 16 times basal levels, although these doses of l-5-hydroxytryptophan alone had only small effects on extracellular 5-HT. The increased formation of 5-HT following l-5-hydroxytryptophan administration appears to overcome homeostatic mechanisms that limit the increases in extracellular 5-HT caused by uptake inhibition.
Platelet activating factor and the responses of rat isolated stomach strip to prostaglandin E2
Authors: Izzo A A , Mascolo N , Autore G , Capasso F 
Published: April 2011

Abstract
The effect of platelet activating factor (PAF) on contractions evoked by acetylcholine, 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) was studied in-vitro on rat stomach strip. Addition of PAF to the organ bath increased PGE- but not 5-HT- or acetylcholine-evoked responses. The effect of PAF was unaffected by atropine, methysergide or indomethacin, but prevented by a specific PAF receptor antagonist BN 52021. The data support a specific interaction between PAF and PGE2 on rat stomach strip.
Synthesis and Inverse Emulsion Polymerization of Aminated Acrylamidodextran
Authors: Daubresse C , Grandfils C , Jéräme R , Teyssié Ph , Goethals P , Schacht E 
Published: April 2011

Abstract
A chemically modified form of dextran was prepared, having a polymerizable moiety (acrylamide) and a reactive functional group (primary amine). Dextran was activated with 4-nitrophenyl-chloroformate (24 mol per polysaccharide, 9·8 mol per 100 glucose residues); 9·8% glucose residues were converted to aliphatic carbonates and 5·2% were converted to cyclic carbonates. The activated dextran was coupled with trityldiaminoethane (8 mol per 100 glucose residues), reactivated with 4-nitrophenylchloro-formate, then coupled with acryloamidodiaminohexane (6·8 mol per 100 glucose residues). The trityl group was removed by hydrolysis with trifluoroacetic acid to yield the required aminated acryloamidodextran. The modified dextran was shown to be polymerizable by inverse emulsion polymerization. Submicron particles were successfully prepared, containing functional amine groups suitable for preparing drug conjugates or for modifying the surface properties of this biomaterial.
Comparative Study on Inclusion Complexation of Maltosyl-β-cyclodextrin, Heptakis(2,6-di-O-methyl)-β-cyclodextrin and β-Cyclodextrin with Fucosterol in Aqueous and Solid State
Authors: Acartürk Füsun , Imai Teruko , Saito Hajime , Ishikawa Masahiro , Otagiri Masaki 
Published: April 2011

Abstract
The complexation of fucosterol with three kinds of β-cyclodextrin (β-CyD) was investigated in aqueous solution and in the solid state. The solubility of fucosterol increased significantly on its complexation with maltosyl-β-CyD and heptakis(2,6-di-O-methyl)-β-CyD (DM-β-CyD), while no appreciable increase was observed when complexed with β-CyD. The stability constant of complexation with β-CyD estimated from solubility determinations was greater for a 1:2 complex than for a 1:1 complex. On the other hand, 1:1 complexation of fucosterol with maltosyl-β-CyD or DM-β-CyD was greater than 1:2 complexation. The solid complexes were obtained in molar ratios of 1:2 and 1:3 for β-CyD and maltosyl-β-CyD complexes, respectively. The inclusion behaviour of fucosterol with maltosyl-β-CyD was compared with β-CyD in the solid state using DSC, powder X-ray diffractometry and CP/MAS 13C NMR. Maltosyl-β-CyD showed different inclusion behaviour compared with β-CyD, and produced an amorphous structure of fucosterol on complex formation. The dissolution rate of fucosterol-maltosyl-β-CyD complex was significantly faster than other complexes due to its high aqueous solubility and amorphous structure.