bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of ethanol dependence on drug responsiveness of mouse isolated vas deferens
Authors: de Moraes Sergio , Capaz Francisco Ruy 
Published: April 2011

Abstract
The effects of ethanol dependence on the responsiveness of the mouse vas deferens to noradrenaline (NA), carbachol, barium and calcium were studied. Ethanol dependence increases the maximum responses to NA and carbachol whereas responsiveness to barium remains unaltered. The concentration-effect curve to calcium was shifted to the left (3·0-fold at the EC50 level). It is concluded that in vas deferens isolated from ethanol-dependent mice the increased responsiveness to NA, carbachol and calcium is a consequence of an enhanced calcium entry through voltage-independent calcium channels, as it has been reported for brain tissue.
Forensic aspects of the metabolism and excretion of cannabinoids following oral ingestion of cannabis resin
Authors: Law B , Mason P A , Moffat A C , Gleadle R I , King L J 
Published: April 2011

Abstract
Following oral ingestion of cannabis resin, δ9-THC−11−oic acid and its O-ester glucuronide were detected using RIA and combined hplc/RIA and shown to be major plasma metabolites of δ9-THC. δ9-THC−11−oic acid was not excreted in the urine in significant concentrations, the glucuronide conjugate being the major urinary metabolite detected. δ9-THC metabolites were detected in blood for up to 5 days and in urine for up to 12 days following a single oral dose of δ9-THC (20 mg). Estimates for the half life of δ9-THC−11−oic acid and its glucuronide in plasma, and total metabolites in urine have been obtained. Interpretation of blood or urine total cannabinoid levels is most difficult, however, drug/metabolite ratios and metabolite/metabolite ratios may have potential for indicating recent cannabis use.
The metabolism of dopamine, NN-dialkylated dopamines and derivatives of the dopamine agonist 2−amino-dihydroxy−1,2,3,4−tetrahydronaphthalene (ADTN) by catechol-O-methyltransferase
Authors: Youde Ian R , Raxworthy Michael J , Gulliver Peter A , Dijkstra Durk , Horn Alan S 
Published: April 2011

Abstract
A variety of dopamine derivatives and analogues were investigated to assess their potential to act as catechol-O-methyltransferase (COMT) substrates using purified, homogeneous pig liver enzyme. This enabled accurate kinetic constants to be determined as opposed to previous in-vivo studies (Rollema et al 1980; Horn et al 1981; Costall et al 1982; Feenstra et al 1983). 2−Amino−6,7−dihydroxy−1,2,3,4−tetrahydronaphthalene (A−6,7−DTN) proved to be a far better substrate (Km = 0·082 mm; Vmax = 300 mu mg−1 protein) than its 5,6−dihydroxy isomer (Km = 2·60 mm; Vmax = 113·9 mu mg−1 protein). This result supports evidence suggesting that differences in brain concentration of these isomers are due to their differential susceptibility to O-methylation by COMT (Rollema et al 1980). A similar result was obtained with a series of NN-di-n-alkyl substituted ADTN derivatives: the same pattern of preferential O-methylation of A−6,7−DTN derivatives over the corresponding A−5,6−DTN isomers was observed. However, increasing the length of the alkyl chain increased the susceptibility of both isomers to metabolism by COMT as shown by a decline in Km. An homologous series of NN-di-n-alkylated dopamines showed a similar trend implying that more hydrophobic compounds are better COMT substrates.
BRL 20459, a novel topically active non-steroidal anti-inflammatory drug
Authors: Green A P , Mangan F R , Thomson M J , Randall K E , Boyle E A 
Published: April 2011

Abstract
BRL 20459 is a novel compound which displays anti-inflammatory activity when applied topically in the croton oil and cantharadin rat ear inflammation models. The compound does not inhibit uv-induced erythema in the guinea-pig or granuloma formation in the cotton pellet test in the rat. BRL 20459 does not inhibit prostaglandin synthesis nor does it interact with corticosteroid receptors in the thymus. In contrast to hydrocortisone, BRL 20459 did not cause thymus involution or reduce body weight gain in rats. BRL 20459 would seem to have a different mechanism of action to hydrocortisone, but this mechanism is as yet unknown.
Cooling-induced contraction in ileal longitudinal smooth muscle of guinea-pig
Authors: Nasu T , Sakai N , Washibe T , Ishida Y 
Published: April 2011

Abstract
The ileal longitudinal smooth muscle developed a transient contraction on cooling from 37 °C to 1 °C in normal Ca2+ (2.5 mm) medium. The transient contraction was not inhibited by pretreatment with the Ca2+ antagonist, D−600 (1 times 10−6 m). The contractions were sustained by cooling to 1 °C in the presence of added Ca2+ greater than 10 mm. After the pretreatment with D−600, when the muscle incubated in normal medium with added 20 mm Ca2+ had been cooled to 1 °C, a phasic response was only seen. However, D−600 did not inhibit the sustained contraction at 1 °C after incubation in the presence of added 20 mm Ca2+. It is suggested that the transient and sustained contraction at 1 °C is maintained by Ca2+ release from a cellular site, probably the cell membrane and it requires more calcium for the sustained tension.
The use of liposomes in the topical application of steroids
Authors: Vermorken A J M , Hukkelhoven M W A C , Vermeesch-Markslag A M G , Goos C M A A , Wirtz P , Ziegenmeyer J 
Published: April 2011

Abstract
The effect of topical application of the androgen 5α-dihydrotestosterone (DHT), both encapsulated in liposomes and solved in acetone, has been evaluated using the female hamster flank organ as a model system. Systemic absorption of DHT was significant from the acetone solution, but negligible from the liposome system. The topical biological effect is, however, proportionally diminished when the liposome system is used. Under the experimental conditions used, the liposome system had no advantages over application in acetone in this model.
Effect of l-dopa on glutamate decarboxylase activity in the hypothalamic and amygdaloid nuclei
Authors: Itoh Masatoshi , Nohtomi Akito , Yufu Nobuo , Uchimua Hideyuki 
Published: April 2011

Abstract
Repeated administration of l-dopa methylester produced a significant increase in glutamate decarboxylase (GAD) activity without pyridoxal-5′-phosphate in the lateral hypothalamic area and medial amygdaloid nucleus. The effect of l-dopa on GAD activity was opposite to that of haloperidol in the lateral hypothalamic area.
Competitive antagonism of α1-adrenoceptor mediated pressor responses in the rat mesenteric artery
Authors: McPherson G A , Coupar I M , Taylor D A 
Published: April 2011

Abstract
(-)-Noradrenaline-mediated pressor responses in the rat mesenteric artery preparation are blocked by α1-adrenoceptor antagonists, BE2254 and prazosin with pA2 values of 8·59 and 8·52 respectively. The α2-adrenoceptor selective antagonist rauwolscine, does not influence responses to (-)-noradrenaline in concentrations up to 10 μm. This rank order is consistent with an α1-adrenoceptor mediated effect. Shifts in the (-)-noradrenaline dose-response curve produced by BE2254 and prazosin were parallel and there was no significant effect on the observed maximal response. Slope values from Schild plots were not significantly different from unity indicating that these antagonists were behaving as classical competitive antagonists.
Comparison between in-vivo and in-vitro tissue-to-plasma unbound concentration ratios (Kp,f) of quinidine in rats
Authors: Harashima Hideyoshi , Sugiyama Yuichi , Sawada Yasufumi , Iga Tatsuji , Hanano Manabu 
Published: April 2011

Abstract
The comparison between in-vivo and in-vitro tissue-to-plasma concentration ratio of drug unbound (Kp,f) has been made using quinidine as a model for weak basic drugs. In-vitro Kp,f-values were calculated from the binding data to tissue homogenates determined by equilibrium dialysis. In-vivo Kp,f-values were calculated from the tissue distribution data after intravenous administration of quinidine, by considering the difference in the unbound concentration between plasma and the tissues produced by the pH difference across the cell membrane. It was concluded that the extensive tissue distribution of quinidine observed in-vivo may be explained by tissue binding and the pH-difference across the cell membrane in most tissues.
Elevation of serum corticosterone in rats by bremazocine, a κ-opioid agonist
Authors: Fuller Ray W , Leander J David 
Published: April 2011

Abstract
Bremazocine at doses of 0·01 mg kg−1 s.c., and higher, increased serum corticosterone concentration several-fold in rats. The increase occurred within 20 min, was maximum at 40–60 min and subsided after 120 min. Pretreatment with naloxone (1–10 mg kg−1 s.c.) antagonized the corticosterone increase. These data support the view that κ-opioid agonist activity of bremazocine mediated the corticosterone increase.
PK 10139 and quinidine: interactions with digoxin concentrations in rats and dogs
Authors: Rougeot C , Jozefczak C , Mestre M , Fur G Le , Uzan A 
Published: April 2011

Abstract
Quinidine induced an increase in digoxin plasma concentrations in rats and dogs. PK 10139, an antiarrhythmic agent 10 times more potent than quinidine, did not change digoxin plasma concentrations in these species. The results indicate that PK 10139 could be associated with digoxin without risk of side-effects.
An in-vitro investigation of drug availability from lipophilic solutions
Authors: Armstrong N A , James K C , Pugh W K L 
Published: April 2011

Abstract
An in-vitro model, previously described, has been modified and used to investigate the effects of volume and concentration on the release of 4-hydroxybenzoic acid from 1-octanol and isopropyl myristate. Solutions encapsulated in soft gelatin shells have also been examined. The quantity of solute released can be increased by reducing the volume of solvent used to prepare the solution, or by increasing the concentration of the solution. The release profile from an encapsulated solution is different from that obtained with the same, unencapsulated solution. The difference is attributed to absorption of the solute by the capsule shell.
Binding of amiodarone by serum proteins and the effects of drugs, hormones and other interacting ligands
Authors: Lalloz M R A , Byfield P G H , Greenwood R M , Himsworth R L 
Published: April 2011

Abstract
Amiodarone is chiefly bound to albumin (62·1%) and much of the remainder (33·5%) is carried on a high molecular weight protein, probably β-lipoprotein. Analysis of data for amiodarone binding to albumin revealed a high affinity primary binding site (Ka 5·6 times 106 litre mol−1) with about four secondary sites (average Ka 1·9 times 105 litre mol−1). Studies of the binding of amiodarone in serum revealed one type of binding site only with an affinity constant (Ka 4·2 times 106 litre mol−1) similar to that of the primary site on albumin. The secondary albumin binding sites do not seem therefore to be utilized in whole serum and the affinity of the lipoprotein must be similar to that of the primary amiodarone binding site on albumin. The effects of a wide range of compounds on albumin binding of amiodarone were examined by equilibrium dialysis. Quinidine, amitriptyline, cephazolin and palmitate decreased albumin-bound [125I]amiodarone. Neither warfarin nor digoxin affected the binding of amiodarone by albumin, thus of the three drugs known to be potentiated by concomitant amiodarone administration, only potentiation of quinidine could be explained by displacement from serum albumin. Rifampicin, frusemide, phenytoin, (-)-adrenaline, bromocresol green, (-)-noradrenaline and bromocresol purple were found to increase binding of [125I]amiodarone by albumin. Amiodarone had no influence on the distribution of iodothyronines amongst their binding proteins nor were the concentration or binding properties of these proteins altered after prolonged treatment with the drug. Thus altered iodothyronine concentrations in amiodarone-treated patients cannot be attributed even in part to effects at the serum binding protein level.
Investigation on central dopaminergic receptors (D-2) using the antagonistic properties of new benzamides
Authors: Rumigny Jean-Francois , Benedetti Margherita Strolin , Dostert Philippe 
Published: April 2011

Abstract
The topography of the central dopaminergic receptor (D−2) has been studied using some analogues of tropapride, a new benzamide derivative, and sulpiride and clebopride as reference drugs. The compounds were compared by testing their ability to compete with [3H]spiperone in an in-vitro binding test and by measuring their potency as antagonists of apomorphine-induced climbing in mice. Tropapride was the most active compound, both in-vitro and in-vivo. With the amide group substituted in the 2−position of the tropane ring, the antidopaminergic activity of the compounds was much less than that of the 3−substituted derivatives. The interaction of the tropane derivatives with the D−2 receptor site is stereoselective as the equatorial stereoisomer was much more active than the axial isomer. The ethylene bridge present in the tropane derivatives but not in the corresponding piperidinyl analogues increases the affinity of the tropane derivatives for the D−2 receptor. Interaction with the D−2 receptor was confirmed as being Na+-dependent. The presence of a benzyl substituent on the basic nitrogen atom seems to be essential in the tropane series emphasizing the important role played in this series by the lipophilic auxiliary binding site postulated in Olson. In conclusion, the tropane skeleton may be considered a useful pharmacophoric group in the design of new dopaminergic drugs.
Histamine responses mediated via H1 and H2−receptors in the isolated portal vein of the dog
Authors: Toshimitsu Yoshinobu , Uchida Kohsuke , Kojima Shu-ichi , Shimo Yasuo 
Published: April 2011

Abstract
The effects of histamine were studied on the isolated circular muscle strip and longitudinal muscle strip of the dog portal vein. Histamine-induced contractions of the circular muscle were inhibited by H1-receptor antagonist pyrilamine but increased by H2-receptor antagonist ranitidine. When the tissues were contracted with PGF2α in the presence of pyrilamine, histamine produced the relaxation of the circular muscle but not longitudinal muscle. The relaxation of the circular muscle was inhibited by ranitidine in a concentration dependent manner, the pA2 value for ranitidine being 6·97 (6·55–7·39). It is concluded that the response of the circular muscle to histamine is the sum of two components, H1-receptor mediated contraction and H2-receptor mediated relaxation.
Pretreatment with aspirin does not influence the pressor response to α2-adrenoceptor agonists in conscious rabbits
Authors: Hannah J A M , Hamilton C A , Reid J L 
Published: April 2011

Abstract
It has proved relatively easy to demonstrate pressor responses mediated via α2-adrenoceptors in-vivo and in whole blood perfused vascular beds, but not in in-vitro work. The possibility that platelet α2-adrenoceptor activation, with subsequent release of vasoactive prostanoids, contributes to the pressor response to α2-adrenoceptor agonists was investigated. The pressor response to the α2-adrenoceptor agonist BHT 920 (Alefexole) was compared in rabbits pretreated with distilled water or aspirin (3 times 200 mg kg−1 by gavage). Aspirin pretreatment had no significant effect on responses to BHT 920; thus, prostanoid formation does not appear to be an important mechanism contributing to postsynaptic α2-adrenoceptor activation.
Haloperidol treatment increases the biosynthesis and release of endorphins in guinea-pig ileum
Authors: MilanéS M V , Vargas M L , Puig M M 
Published: April 2011

Abstract
Guinea-pigs treated acutely (5 mg kg−1 i.p.) and chronically (2 or 5 mg kg−1 day−1 for 4 days) with haloperidol, show an increase of the inhibitory response produced by electrical stimulation at 10 Hz of the ileum myenteric plexus-longitudinal muscle (MPLM) preparation. The response can be reversed by the specific narcotic antagonist naloxone (5 times 10−7 m), which suggests that the increase in the response produced by haloperidol is mediated by release of endorphins. When haloperidol-treated guinea-pigs received cycloheximide (24 and 12 h before death), there was a substantial decrease in the response indicating that the biosynthesis and release of endorphins are increased by haloperidol.
Potentiation by sulphydryl agents of the responses of guinea-pig isolated ileum to various agonists
Authors: Fontaine Jeanine , Famaey Jean-Pierre , Reuse Jean 
Published: April 2011

Abstract
Sulphydryl agents (dithiothreitol, mercaptoethanol, monothioglycerol, cysteine, glutathione) increase non-specifically the potency of various agonists (acetylcholine, 5-hydroxytryptamine, nicotine, bradykinin, prostaglandin E2) on the guinea-pig ileum. These effects are of non-cholinergic origin and are not related to prostaglandin synthesis. Sulphydryl agents act directly on the smooth muscle cells of the guinea-pig ileum most probably by reducing disulphide bonds located on the membrane surface and by this mechanism modulate the muscular contractile activity.
Effect of dopamine on dog distal colon in-vitro
Authors: Grivegnée A R , Fontaine J , Reuse J 
Published: April 2011

Abstract
The effects of dopamine, isoprenaline, adrenaline and noradrenaline in dog isolated colon strips were studied. All these drugs produced in the preparation relaxations which were inhibited by propranolol and sotalol or, in the case of noradrenaline, by a mixture of propranolol and phentolamine. A selective β1-adrenergic antagonist, practolol, had the same inhibitory effects on the relaxations induced by all the agonists, suggesting the existence of β1- and β2-adrenoceptor subtypes in the dog distal colon. There is no evidence for the presence of specific dopaminergic receptors in this preparation.
Rifampicin curing of plasmids in Escherichia coli K12−rifampicin resistant host
Authors: Obaseiki-Ebor E E 
Published: April 2011

Abstract
The in-vitro rifampicin curing of R-plasmids JR225, BN102, BN106 and F’-plasmid F’lac+/R386 in Escherichia coli K12 rifampicin-resistant host J62–2 is described. The minimum rifampicin curing concentration and the frequency of curing of plasmids from the rifampicin-resistant host cell J62–2 and the isogenic rifampicin-sensitive J62–1 host cell were similar. However, rifampicin did not cure some test R-plasmids such as R222 and RP4 from rifampicin-resistant and rifampicin-sensitive host cells, indicating that it is the R-plasmid itself and not the host strain that determines rifampicin curing.
Antipropulsive effects of central and peripheral morphine in the rat gastrointestinal tract
Authors: Stewart John J , Curd Cheryl D 
Published: April 2011

Abstract
The antipropulsive effects of centrally or peripherally administered morphine have been examined at three levels of the rat gastrointestinal tract. Adult male rats were anaesthetized with pentobarbitone (50 mg kg−1 i.p.) and were implanted with an intraluminal catheter in either the proximal duodenum or mid-jejunum. Other animals were also implanted with a cannula in the right lateral cerebral ventricle. Gastric emptying and transit were determined selectively by measuring the progression of a radioactive chromium (CR-51) solution, given intragastrically for tests of gastric emptying or instilled into the proximal or distal intestinal catheter for determination of intestinal transit, 30 min after administration of morphine or saline given either subcutaneously (s.c.) or intracerebroventricularly (i.c.v.). Morphine given either s.c. (5 mg kg−1) or i.c.v. (30 μg, total dose) significantly inhibited gastric emptying and transit through bulk portions of the small intestine indicating that by either route it inhibits propulsion at all three levels of the gastrointestinal tract.
The pinna reflex and its inhibition by clonidine: Relationship to sedation and quantitation of central α2-antagonist potency
Authors: Handley Sheila L 
Published: April 2011

Abstract
The relationship between sedation and pinna reflex inhibition has been measured for a range of centrally acting drugs. Ability to abolish the pinna reflex was not related to sedative activity as assessed by a behavioural method. Thus, at equisedative doses, diazepam, haloperidol, mianserin, prazosin and indoramin failed to abolish the pinna reflex while phenobarbitone and chlorpromazine caused partial- and clonidine complete-inhibition. At the ED50 for pinna reflex inhibition, guanabenz and guanfacine were significantly less sedative than clonidine. Mepyramine, yohimbine, RS−21361, idazoxan and phenylephrine produced little or no sedation and did not inhibit the reflex. When these agents (except for guanabenz and guanfacine) were tested for their ability to prevent clonidine-induced pinna reflex inhibition, all except the drugs with α2-adrenoceptor antagonist activity were inactive. The potency order of the active agents was idazoxan &gt; yohimbine &gt; RS−21361 = mianserin. Antagonism of clonidine-induced pinna reflex inhibition may therefore prove to be a useful quantitative model for assessing the central potency of α2-adrenoceptor antagonists.
Central pressor activity of cimetidine in spontaneously hypertensive rats
Authors: Dadkar N K , Aroskar V A , Gupte R D , Dohadwalla A N 
Published: April 2011

Abstract
The systemic blood pressure effect of cimetidine given intracerebroventricularly (i.c.v.) in anaesthetized spontaneously hypertensive (SH) rats has been investigated. Cimetidine (250 μg i.c.v.) caused a gradual long lasting rise in mean in mean arterial blood pressure with maximum of 31·6 ± 4·5 mm Hg. Chemical degeneration of catecholaminergic neurons with 6−OHDA treatment, central administration of phentolamine and prazosin, and the bilaterial adrenalectomy significantly inhibited the pressor response of cimetidine, while propranolol (i.c.v.) had no effect. From these results it appears that the hypertensive response of cimetidine is mediated by central catecholaminergic pathways and is due to an increase in efferent sympathetic outflow and release of catecholamine from the adrenal medulla.
Theoretical estimation of punch velocities and displacements of single-punch and rotary tablet machines
Authors: Charlton B , Newton J M 
Published: April 2011

Abstract
The speed of travel of punches during compaction by a Manesty F3 single punch and D3B Rotary punch tablet machine has been derived from machine dimensions, normal operating speeds and by consideration of the consolidation of a theoretical compact. The analysis may also be used for machines with other dimensions, operating at different speeds with other materials, but would require modification if the punch head design on the rotary machine differed significantly. Punch speeds at the beginning of the compression cycle were similar for the two types of machines, namely 10·36 and 10·24 cm s−1 for the single and rotary machines. The time to reach maximum compression and the total time of contact between punches and powder for the single punch machine was 0·1 s for a compaction force of approximately 40 KN. For the rotary machine operating at approximately the same force, these two parameters were found to be 0·052 and 0·083 s respectively. The additional contact time is associated with a period during which there is no vertical movement of the punch, providing a ‘dwell’ time of 0·0314 s when the powder is held at a constant volume.