bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine-mediated behaviours produced in naive mice by bromocriptine plus SKF 38393
Authors: Jackson D M , Ross S B , Hashizume Mayko 
Published: April 2011

Abstract
The ability of bromocriptine and SKF38393 (2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepine) to produce some dopamine-mediated behaviours has been assessed in mice. Soon after injection, SKF38393 produced moderate increases in grooming and sniffing which were not very intense, while bromocriptine (with or without SKF38393) inhibited all grooming behaviour. Bromocriptine alone also depressed rearing and sniffing in the first hour and SKF38393 alone was without effect on rearing, but the combination produced a marked increase in the incidence of both rearing and sniffing, both of which behaviours appeared to be stereotyped. When bromocriptine-induced locomotor stimulation was peaking about 3 h after injection, as measured in automated activity cages in previous studies, there was an increase in sniffing and rearing, the incidence of which was unaffected by the addition of SKF38393, perhaps due to the shorter duration of action of SKF38393 than of bromocriptine. The data indicate that the D-1 agonist SKF38393 can qualitatively and quantitatively alter the behavioural spectrum produced by the D-2 agonist bromocriptine.
Study with Positron Emission Tomography of the Osmotic Opening of the Dog Blood-Brain Barrier for Quinidine and Morphine
Authors: Agon Philippe , Kaufman Jean-Marc , Goethals Patrick , van Haver Dirk , Bogaert Marc G 
Published: April 2011

Abstract
A canine model was used to evaluate the possibilities offered by positron emission tomography (PET) for the study of drug distribution in the brain during altered states of the blood-brain barrier (BBB). PET was used to monitor the changes in the distribution of [11C]quinidine and [11C]morphine resulting from BBB-disruption by intracarotid infusion of a hyperosmolar mannitol solution. Injection of Evans blue dye allowing post-mortem evaluation of the degree of BBB-opening was used as a reference method. Brain radioactivity concentrations observed after i.v. injection of either [11C]quinidine or [11C]morphine were markedly increased by intracarotid mannitol infusion, whereas they were not affected by saline infusion. For both drugs a close correlation was found between the radioactivity concentrations and the degree of Evans blue staining within the brain hemispheres and within smaller regions of interest corresponding to quadrants of a hemisphere. This parallelism between the findings for radioactivity concentrations and Evans blue staining suggests that PET allows the detection of in-vivo changes in brain distribution of drugs resulting from alterations of the BBB permeability.
Effects of BN 52063 and other agents inhibiting platelet-activating factor-induced contractile responses in rat portal vein
Authors: Hellegouarch A , Auguet M , Clostre F , Braquet P 
Published: April 2011

Abstract
Platelet-activating factor (PAF-acether) is a potent agonist (EC50: 3.2 × I0−8 M) of isolated rat portal vein. BN 52063 (composed of BN 52020, BN 52021 and BN 52022; molar ratio 2:2:1) specifically inhibits PAF-acether (10−7 M) induced tone (IC50: 3.9 × 10−5 M). Salbutamol (IC50: 3.1 × 10−7 M), forskolin (IC50:3.1 × 10−6M) and theophylline (IC50: 2.25 × 10−4M) are also effective in inhibiting PAF-acether-induced contractile responses and all excepting forskolin, show a certain specificity in this action. The basal myogenic activity of the rat portal vein is dose-dependently decreased by salbutamol (IC50: 1.2 × 10−7M), forskolin (IC50: 2.6 × 10−4M) and theophylline (IC50: 2.3 × 10−4 M) whereas BN 52063 has no effect. The data suggest that rat portal veins possess specific PAF-acether receptors sensitive to BN 52063 and that PAF-acether effects could be inhibited by compounds which can bypass these putative receptors and modulate cAMP levels.
Circadian phase-dependent pharmacokinetics and acute toxicity of mepivacaine
Authors: Bruguerolle Bernard , Prat Marin 
Published: April 2011

Abstract
The aim of this study was to investigate the possible influence of the time of administration on mepivacaine acute toxicity and kinetics in mice. Four different groups of adult male NMRI mice maintained under controlled environmental conditions (lights on: = 0600–1800 h) were injected at one of the following times: 1000, 1600, 1900, 2200, 0100 and 0400 h with one of four doses of mepivacaine at each time point to establish the acute toxicity (LD50). To assess chronokinetics, a single 60 mg kg−1 i.p. dose of mepivacaine was given to adult male NMRI mice at four fixed times: 1000, 1600, 2200 and 0400 h. Mepivacaine plasma concentrations were determined by GLC. Our data showed significant 24 h variations in the following parameters: Highest tmax value = 0.366 ± 0.073 h at 1000 h (P &lt; 0005, amplitude, maximum-minimum/mean × 100, = 184%), highest Cmax/tmax ratio = 177.17 ± 9.49 at 2200 h (P &lt; 0005, amplitude = 192%), highest Vd = 0.842 ± 0.23 L kg−1 at 2200 h (P &lt; 0005, amplitude = 158%) and highest β phase elimination half-life = 5.408 ± 1.36 h at 2200 h (P &lt; 0.025, amplitude = 145%). Cmax (amplitude = 15%), AUCox (amplitude = 24%) and clearance (amplitude = 23%) were not significantly time-dependent. These data demonstrate a temporal pattern of mepivacaine kinetics similar to those reported previously for bupivacaine. The temporal changes in mepivacaine-induced acute toxicity may result in part from its chronokinetic changes.
Oesophageal transit of small tablets
Authors: Robertson Charles S , Hardy John G 
Published: April 2011

Abstract
Oesophageal transit has been studied in six asymptomatic subjects aged 29–80 years. Using gamma scintigraphy, the transit of a liquid and five small tablets was monitored in each subject. All the subjects exhibited normal liquid swallowing, with 50% oesophageal clearance times of less than 5 s. In three subjects all the tablets passed through the oesophagus within 6 s, but transit was prolonged in 60% of the swallows in the other subjects. Tablet hold up occurred more frequently in the elderly. An additional drink of water cleared all lodged tablets into the stomach. To minimize possible mucosal irritation, the taking of even small tablets should be followed by an additional drink of water.
The Sorption of Isosorbide Dinitrate to Intravenous Delivery Systems
Authors: de Muynck C , Remon J P , Colardyn F 
Published: April 2011

Abstract
The sorption of isosorbide dinitrate from 0.9% sodium chloride and 10% glucose solutions, by intravenous delivery systems has been investigated under simulated infusion conditions. Isosorbide dinitrate was stable in both 0.9% sodium chloride and 10% glucose solutions. Intravenous fluid containers, burettes, a syringe, infusion sets and end-line filters were evaluated. Glass containers, methacrylate butadiene styrene burettes and polybutadiene giving sets did not sorb isosorbide dinitrate. Neither did polypropylene syringes when a 10% glucose solution was used. The sorption of isosorbide dinitrate to end-line filters was unimportant but there was a significant loss to the PVC tubing used to connect the filter housing to the catheter.
Structure-Activity Studies of Fentanyl
Authors: Casy A F , Huckstep M R 
Published: April 2011

Abstract
The preparation of analogues of fentanyl with para substituents in the anilino aromatic ring, anilino nitrogen separated from phenyl by methylene or bimethylene, and phenacyl replacing propionyl as the N-acyl substituent is reported. Although all para substituents examined depressed antinociceptive potency in rats, most analogues of this kind were more effective than morphine and the p-F, I, and Me derivatives were only a few-fold less active than fentanyl. Separation of anilino nitrogen from phenyl lowered potency with N-phenethyl analogues retaining reasonable levels of activity (&gt; morphine). All the phenacyl analogues were of low potency or inactive. Diagnostic details of the mass spectra of analogues likely to be encountered as ‘designer drugs’ are appended.
Dihydroergotoxine-induced Bradycardia in Rats
Authors: Roquebert Jacques , Grenié Bruno 
Published: April 2011

Abstract
Dihydroergotoxine (0.01–0.3 mg kg−1 i.v.) decreased heart rate in pentobarbitone-anaesthetized rats. The bradycardia was reduced but not blocked by pre-treatment with guanethidine, yohimbine, propranolol or pithing. It was not prevented by bivagotomy, atropine, sulpiride or haloperidol. Dihydroergotoxine failed to affect, either the bradycardia produced by electrical stimulation of the vagus, or the cardioacceleration induced by i.v. isoprenaline. The increase in heart rate elicited in pithed rats by electrical stimulation of the spinal cord was reduced by dihydroergotoxine; this effect being inhibited by yohimbine but not by sulpiride. In conclusion, the main mechanism by which dihydroergotoxine (i.v.) induces bradycardia in the rat involves stimulation of α2-adrenoceptors located predominantly at the cardiac sympathetic nerve endings.
The stability of morphine in isobaric and hyperbaric solutions in a drug delivery system
Authors: Caute B , Monsarrat B , Lazorthes Y , Cros J , Bastide R 
Published: April 2011

Abstract
Intrathecal preparations of morphine for use in intractable pain must contain no preservatives. They are generally formulated in saline (isobaric) or dextrose (hyperbaric) which raises questions of stability. The behaviour of morphine in hyperbaric and isobaric solutions stored in a reservoir for implantation has been examined and the effect of temperature and the time of contact of morphine with the different components of the reservoir as well as the sterilization procedure have been investigated. The best stability was observed with a hyperbaric solution in which there was 15 to 20 times less pseudomorphine than in the isobaric solution, which was found to contain 1% pseudomorphine after 1 month of storage at 37 °C in the reservoir. Similar solutions stored in ampoules did not degrade.
Effects of Phosphatidylcholine on the Topical Bioavailability of Corticosteroids Assessed by the Human Skin Blanching Assay
Authors: Jacobs M , Martin G P , Marriott C 
Published: April 2011

Abstract
A non-occluded multiple application skin blanching assay has been used to determine the effect of applied phosphatidylcholine (PC) on the bioavailability of corticosteroids. One forearm of each often volunteers was treated twice daily for one week with PC presented as a liposomal suspension in Sørensen’s (pH 5.0) phosphate buffer (2.5 mg PC/0.5 mL) while the other arm was treated with 0.5 mL of phosphate buffer. For the following two weeks this treatment regimen was continued but in addition, each of four corticosteroid formulations (containing (i) hydrocortisone 0.1%, (ii) clobetasone butyrate 0.05%, (iii) betamethasone 0.1 % and (iv) clobetasol propionate, 0.05%) was applied to sites on both arms. 5 ± 1 mg of each cream was applied twice daily to the sites on day 1, then once daily for a further four days; after two days of no application, the protocol was repeated. Estimation of pallor was usually made four times daily. At the end of the second week of corticosteroid application the blanching response to all four formulations on the PC treated arms was significantly higher than on the buffer treated arm. Tachyphylaxis to the applied corticosteroids was markedly less apparent on the lipid-treated arms. It is proposed that the applied phospholipid either supplements the lipid content of the skin or provides a thin film in intimate epidermal contact. Such a film may promote hydration of the stratum corneum and also provide an environment into which corticosteroids initially partition before a subsequent, more controlled, release to the underlying tissue.
β2-Adrenoceptor influences on the α1- and α2-mediated vasoconstriction induced by phenylpropanolamine and its two component enantiomers in the pithed rat
Authors: Moya-Huff Fernando A , Maher Timothy J 
Published: April 2011

Abstract
Phenylpropanolamine (PPA, (±)-norephedrine) is commonly found in appetite suppressants and nasal decongestants. Within the cardiovascular system of the pithed rat, the drug and its two component enantiomers ((−)- and (+)-norephedrine) are largely direct-acting agonists. The interaction between simultaneous α1-, α2- and β2-adrenoceptor mediated effects of the drug and its two enantiomers have been examined using the cardiovascular system of the pithed rat. On all adrenoceptors tested the potency was (−)- &gt; (±)-, &gt; (+)-norphedrine. The α1- and α2-mediated pressor responses of each were enhanced in the presence of the β2-adrenoceptor antagonist, ICI 118,551, and diminished in the presence of the selective β2-adrenoceptor agonist salbutamol. It is concluded that each form of the drug possesses the intrinsic ability to interact with the α1-, α2- and β2-adrenoceptors in the system used and that the interaction with those adrenoceptors determines the net increase in diastolic blood pressure that follows the intravenous administration of the compounds. These findings have a bearing on the recent controversy regarding the use of β-blocking agents in the treatment of overdosage of the drug.
Senna still causes laxation in rats maintained on a diet deficient in essential fatty acids
Authors: Mascolo N , Meli R , Autore G , Capasso F 
Published: April 2011

Abstract
The laxative effect of senna has been investigated in normal and essential fatty acid deficient (EFAD) rats. Oral administration of senna pod extract (7-5-90 mg kg−1) produced a dose-dependent increase in the number of soft faeces excreted by normal rats. Senna 30 mg kg−1 also reversed net absorption of water and increased the prostaglandin (PG) production in the colonic lumen of normal rats by about four times. Oral administration of senna pod extract to rats, maintained on a fat-free diet for 30–90 days, produced diarrhoea and reversed net absorption of water as in normal rats. However, a fat-free diet reduced the PG production drastically in the colonic lumen both in senna-free rats and in senna-treated rats. In EFAD rats carrageenan oedema, but not dextran oedema, was also drastically reduced. Since PG mediation is not present in EFAD rats we conclude that the PG are not essential for laxation induced by senna and that water secretion and PG production in the rat intestinal lumen are unrelated.
Effect of Meptazinol on Evoked Responses in Rat Vas Deferens
Authors: Charlton J , Hughes I E 
Published: April 2011

Abstract
Responses of rat isolated vas deferens to electrical stimulation through field electrodes (400 mA, 1 ms duration, single shocks at 5 min intervals) were potentiated by meptazinol (10 to 300 μM) in whole tissues and also in the separated prostatic and epididymal portions. The effect was fast in onset, reproducible and easily reversed by washing. Prazosin (0·1 μM) practically abolished the response of the epididymal portion to electrical stimulation while the response of the prostatic portion was only slightly reduced (&lt;20%). In the presence of prazosin, meptazinol still produced potentiation of the response of the prostatic portion. Nifedipine (2 μM) practically abolished the response of the prostatic portion to electrical stimulation while the response of the epididymal portion was only slightly reduced (&lt;20%). In the presence of nifedipine, meptazinol no longer produced potentiation of the response of the epididymal portion. Exogenous ATP (5 μM to 1 mM) and phenylephrine (1 to 50 μm) produced a contractile response which was potentiated in the presence of meptazinol (100 μM) but in the presence of meptazinol (100 μM) and nifedipine (5 mM) together, potentiation of phenylephrine no longer occurred. It is suggested that potentiation by meptazinol of electrically induced responses in this tissue is due to a direct action on the smooth muscle.
Suppression of pentobarbitone-induced hyperactivity by past experience in mice
Authors: Sansone Mario , Pavone Flaminia , Battaglia Mario , Vetulani Jerzy 
Published: April 2011

Abstract
Locomotor activity of CD-1 mice, tested in an unfamiliar environment (toggle-floor box), was increased either by a subhypnotic dose (20 mg kg−1) of pentobarbitone or after recovery from pentobarbitone-induced (50 mg kg−1) anaesthesia. On the contrary, when mice were tested 6 h after a single exposure to the apparatus, pentobarbitone in either case failed to produce hyperactivity. The results demonstrate that mice recovering from barbiturate anaesthesia maintain susceptibility to the exteroceptive stimuli provided by a novel environment and knowledge of the environment acquired during past experience.
Factors in snake venoms that increase capillary permeability
Authors: Miller Roger A , Tu Anthony T 
Published: April 2011

Abstract
Capillary permeability increasing (CPI) activity is a phenomenon of the microvasculature caused by many agents such as snake venoms, histamine, 5-hydroxytryptamine (5-HT), prostaglandins and leukotrienes. Since no systematic study has been done to determine what components of snake venom cause CPI activity, a CPI factor from Naja naja atra (Taiwan cobra) venom was isolated using intravenous injections of Evan’s blue dye as the indicator of increased permeability and the factor’s properties were extensively studied. Cardiotoxin from Naja naja kaouthia (Thailand cobra) and Mojave toxin from Crotalus scutulatus scutulatus (Mojave rattlesnake) venoms demonstrated CPI activity. Postsynaptic neurotoxins from an elapid and a hydrophid and myotoxin a from Crotalus viridis viridis (prairie rattlesnake) showed no CPI activity at the dose studied. The purified CPI active component from Naja naja atra venom was found to have cardiotoxic activity. Therefore, Elapidae cardiotoxins are CPI active factors. However, CPI activity is not due to cardiotoxins alone as the presynaptic neurotoxin, Mojave toxin, also showed CPI activity. Selective inhibitors were used to indicate possible mechanisms of action on the capillaries by Naja naja atra venom and Crotalus scutulatus scutulatus venom. The histamine H1-receptor blockers diphenhydramine, promethazine, and cyproheptadine were effective against both venoms in preventing increased capillary permeability. These results suggested that histamine release activity is the most likely mechanism resulting in CPI activity from these venoms.
The systemic availability of buprenorphine administered by nasal spray
Authors: Eriksen Jørgen , Jensen Niels-Henrik , Kamp-Jensen Michael , Bjarnø Helle , Friis Poul , Brewster David 
Published: April 2011

Abstract
The kinetics and systemic bioavailability of intranasally administered buprenorphine have been investigated in 9 healthy volunteers in an intranasal/intravenous cross-over study. Each subject received a nominal 0·3 mg dose of buprenorphine intranasally followed one week later by a matched dose intravenously. For the intranasal administration mean tmax and mean Cmax were 30·6 min and 1·77 ng mL−1, respectively. Mean intranasal bioavailability was 48·2 ± 8·3% (mean ± s.e.m.) of the intravenous value. Intranasal administration may represent a valuable new delivery route for buprenorphine.
Decreased 5-hydroxytryptamine turnover in striatum and other brain regions after administration of 5-methoxy-3-(di-n-propylamino)-chroman to rats
Authors: Fuller Ray W , Perry Kenneth W , Ward John S 
Published: April 2011

Abstract
5-Methoxy-3-(di-n-propylamino)chroman (5-MeO-DPAC) caused a dose-dependent decrease in the accumulation of 5-hydroxytryptophan after decarboxylase inhibition in rat striatum, hippocampus and frontal cortex. The decreased 5-hydroxytryptamine (5-HT) turnover may have resulted from activation of 5-HT receptors on cell bodies of 5-HT neurons that project to the striatum and other brain regions, since 5-MeO-DPAC had earlier been reported to lack affinity for striatal binding sites.
[3H]Acetylcholine Release from the Guinea-pig Distal Colon: Comparison with Ileal [3H]Acetylcholine Release and Effect of Adrenoceptor Stimulation
Authors: Marcoli Manuela , De Ponti Fabrizio , Lecchini Sergio , Crema Antonio , Frigo Gian Mario 
Published: April 2011

Abstract
To study cholinergic function in the guinea-pig colon, resting and electrically evoked 3H release after preincubation with [3H] choline has been compared in colonic and ileal myenteric plexus preparations. Fractional spontaneous colonic 3H release was significantly higher than ileal 3H release, while the reverse was true for electrically evoked 3H outflow. Electrically evoked 3H outflow in the colon was linearly related to stimulation frequency (0·2–3 Hz range) and current intensity (300–600 mA range), while 3H outflow per pulse was inversely related to stimulation frequency. Electrically evoked 3H outflow was prevented in Ca2+-free solution, indicating that it probably mirrored neuronal exocytotic [3H]acetylcholine release. Both noradrenaline and clonidine concentration-dependently inhibited electrically evoked 3H outflow, Clonidine being more potent but less efficacious than noradrenaline. For both noradrenaline and Clonidine, the potency and efficacy for inhibition of 3H outflow were close to the values previously reported for the inhibition of electrically evoked endogenous acetylcholine output from colonic preparations. In conclusion, these data indicate that 3H release after incubation with [3H]choline is a valid alternative to measurement of endogenous acetylcholine output to study colonic cholinergic neuronal function in the guinea-pig.
Anaesthetic Concentrations of Enflurane and Methoxyflurane in Rat Brain In-vivo and In-vitro
Authors: Bazil Carl W , Minneman Kenneth P 
Published: April 2011

Abstract
We measured concentrations of enflurane and methoxyflurane in brains of anaesthetized rats and established conditions for reproducing these concentrations in brain tissue in-vitro. Despite a 12-fold difference in inspired potency, brain concentrations resulting in anaesthesia were similar for both compounds. However, substantially lower concentrations in the equilibrating gas were necessary to achieve similar tissue concentrations in-vitro, probably because anaesthetic-induced respiratory depression or changes in cardiac output causes incomplete equilibration in-vivo. These studies provide direct evidence that brain concentrations associated with anaesthesia are similar for anaesthetics with different inspired potencies. They also suggest that lower concentrations in the equilibrating gas should be used in-vitro to reproduce clinically relevant tissue concentrations that are necessary to cause anaesthesia in-vivo.
Correlation Between Hydrophobicity of N-Alkylxanthine Derivatives and their Biological Activities on Guinea-pig Isolated Tracheal Smooth Muscle
Authors: Miyamoto K , Takagi K , Sakai R , Wakusawa S , Koshiura R , Nadai M , Apichartpichean R , Hasegawa T 
Published: April 2011

Abstract
Cyclic (c) AMP phosphodiesterase (PDE) inhibitory activities of N-alkylxanthine derivatives (3-methyl-, 3-ethyl-, 3-propyl-, 3-butyl-, 1,3-dimethyl-, 1-methyl-3-ethyl-, 1-methyl-3-propyl-and 1-methyl-3-butyl xanthines) and their relaxant effects on carbachol-induced contraction and on resting tone guinea-pig isolated tracheal smooth muscle have been investigated. The PDE inhibition constant (Ki) and the concentration producing 50% tracheal smooth muscle relaxation in-vitro (EC50) were determined. Significant correlations between the -log Ki values and the -log EC50 values on the carbachol-induced contraction or on the resting tone were found (r = 0·902 and 0·892). The apparent partition coefficient (P) between n-octanol and pH 7·4 phosphate-buffered saline (PBS) was measured as an index of hydrophobicity of the xanthine derivatives. There were significant correlations between log P and both -log EC50 values and between the log P and -log Ki values. These findings suggest that the cAMP PDE inhibitory activity of N-alkylxanthine derivatives contributes to the mechanism of bronchodilatory action, and that an increase in hydrophobicity of the xanthine molecule enhances the biological activity.