bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naltrexone metabolism and sustained release following administration of an insoluble complex to rhesus monkeys and guinea-pigs
Authors: MacGregor Thomas R , Drum Mary A , Harrigan Stephen E , Wiley James N , Reuning Richard H 
Published: April 2011

Abstract
Both the release and the metabolism of naltrexone have been evaluated after intramuscular administration of a sustained release [15,16-3H2]naltrexone aluminium tannate complex in guinea-pigs and rhesus monkeys. In both species, measurable excretion of radioactivity was obtained for &lt; 50 days and complete recovery of the dose was obtained in the guinea-pig. The radioactivity excretion rate-time profile differed in the two species with guinea-pig yielding a continuously declining rate and monkey yielding a peak at 5 days. In selected monkey urine samples (days 4,17–20 and 49–52) subjected to t.l.c., evidence was obtained for the presence of naltrexone, β-naltrexol and 2-hydroxy-3-O-methyl-β-naltrexol, mostly as glucuronide and/or sulphate conjugates. The t.l.c. data also suggest that in monkey a naltrexone metabolite builds up relative to naltrexone over the 52 day release period.
Physical factors affecting microencapsulation by simple coacervation of gelatin
Authors: Siddiqui Ovais , Taylor Harry 
Published: April 2011

Abstract
Gelatin has been coacervated at 60 †C using sodium sulphate. Interfacial tensions between coacervate and supernatant liquid, coacervate and two oils (with and without one of two drugs, clofibrate and chlormethiazole) and supernatant liquid and the oils (± drug) have been measured by a drop volume technique, in the presence and absence of one of three surfactants, cetrimide, sodium lauryl sulphate and hexadecyltrimethylammonium lauryl sulphate (double salt). Spreading coefficients calculated from tensions indicate that coacervate should spread readily over oil droplets in presence of double salt, less readily with cetrimide and spreading is unlikely in the presence of sodium lauryl sulphate. The sign of the charge on coacervate droplets and oil droplets was identified under different conditions and showed coacervate droplets and oil droplets have opposite charges except in the presence of sodium lauryl sulphate. Microcapsules were prepared using cetrimide or ‘double salt’ as emulsifier and release of drug measured. Those prepared with ‘double salt’ released more slowly than those prepared with cetrimide.
Capsule filling studies using an mG2 production machine
Authors: Jolliffe I G , Newton J M 
Published: April 2011

Abstract
A production mG2 G36 machine has been employed to study the effects of compression on the capsule filling properties of four particle size fractions of lactose having a range of flow properties. The effect of the surface texture of the dosator nozzle bore on capsule filling is also investigated. Fine, cohesive powders gave uniform fill weights over a whole range of compression settings but as increasingly free-flowing powders were used, this range diminishes. For both types of powder, the upper limit on compression is set by compaction of powder which produces poor fill weights; coarse, free-flowing powders, which are less compressible, compact at lower compressions. Free-flowing powders, in particular, also require a minimum compression to be retained. Resurfaced nozzles produced improved capsule filling. One nozzle surface produced slightly more uniform fill weights and was unaffected by powder coating of the nozzle suggesting that an optimum surface texture exists for capsule filling. The results are similar to those obtained using the mG2 simulator and hence validate the latter’s use in studying production capsule filling.
Photosensitization by fluorescein dyes and tetracycline drugs at an oil/water interface
Authors: Riaz M , Pilpel N 
Published: April 2011

Abstract
Measurements were made of the changes that occur in the interfacial tension of isopropylbenzene when floating on water containing between 10−5 and 10−3 M of various fluorescein dyes and tetracycline drugs and irradiated for up to 240 min with ultraviolet light. Singlet oxygen was found to be an active intermediate in the reactions. The results are discussed in relation to adverse photosensitization in-vivo due to fluorescein dyes and tetracycline drugs.
The influence of deposition method on the packing uniformity of powder beds
Authors: Woodhead P J , Newton J M 
Published: April 2011

Abstract
A number of methods of preparing powder packings have been assessed in terms of the resulting variability of local porosity. Measurement of local porosity was carried out by a γ-ray attenuation technique. It was found that overall porosity and the distribution of local porosity were highly dependent on particle properties and deposition method. Some deposition methods tended to give rise to the alternate formation and collapse of temporary structures within a growing bed, and in such cases, relatively high variability of local porosity was detected. More uniform packings could be formed by deposition of powder in even layers. In many cases, a significant relationship between local porosity and position within a packing was established, the central areas generally being of lowest porosity. This was true of packings both of high and low overall variability of porosity.
Enhancement of rectal absorption of insulin using salicylates in dogs
Authors: Nishihata Toshiaki , Rytting J Howard , Kamada Akira , Higuchi Takeru , Routh Mack , Caldwell Larry 
Published: April 2011

Abstract
Sodium salicylate and 5-methoxysalicylate both increased the rectal absorption of insulin in dogs when co-administered with insulin in various formulations. Microenema formulations containing 4% gelatin showed the highest insulin biavailability of the formulations studied whereas microenemas (without gelatin) and suppository formulations were not as effective in enhancing the rectal absorption of insulin.
HI6 as an antidote to soman poisoning in rhesus monkey respiratory muscles in-vitro
Authors: Smith A P , Wolthuis O L 
Published: April 2011

Abstract
This study was carried out to evaluate the rhesus monkey as a model for man with respect to oxime-induced acetylcholinesterase reactivation as a mechanism contributing to restoration of soman poisoned neuromuscular function. In-vitro neuromuscular blockade in intercostal and diaphragm muscle strips of rhesus monkeys was induced by exposing them for 2.5 or 15 min to the cholinesterase inhibitor soman. Subsequent treatment with the oxime HI6 produced only a partial reversal of this blockade. Only a minor part of the recovery obtained could be attributed to enzyme reactivation and suggested that this species responded in a manner closer to that reported in man than other animal species studied.
Different stereoselective inhibition of monoamine oxidase-B by the R- and S-enantiomers of MD 780236
Authors: Dostert P , Benedetti M Strolin , Guffroy C 
Published: April 2011

Abstract
MD 780236, a selective inhibitor of the B form of MAO behaves as an irreversible inhibitor in in-vitro conditions and mainly as a short-acting inhibitor in ex-vivo experiments. The enantiomer with the R absolute configuration (MD 240928) is fully reversible in ex-vivo conditions, whereas the S-enantiomer (MD 240931) has kept the irreversible component of the inhibition seen with MD 780236. The corresponding racemic alcohol derivative (MD 760548) is also a short-acting inhibitor of the B form of MAO; its S-enantiomer, which has an absolute configuration corresponding to that of MD 240928, has a selectivity towards the B form superior to that of the other enantiomer. The mechanism of the MAO inhibition by MD 780236 is discussed.
Enhanced effect of haloperidol and apomorphine after hypophysectomy: pharmacokinetic considerations
Authors: Lloyd K G , Bianchetti G , Worms P , Morselli P L 
Published: April 2011

Abstract
The behavioural effects of both apomorphine (stereotypies) and haloperidol (catalepsy and reversal of stereotypies) were significantly enhanced in hypophysectomized rats compared with sham-operated rats. Both the efficacy and duration of action were increased. Hypophysectomized animals had significantly greater brain haloperidol concentrations than did sham-operated animals. The data suggest that changes in brain drug concentrations following hypophysectomy at least partially explain the behavioural alterations seen in this test situation.
The metabolism and biosynthesis of (±)-o-octopamine and (±)-o-synephrine in the rat
Authors: James Michael I , Midgley John M , Williams Clyde M 
Published: April 2011

Abstract
The metabolism of (±)-o-octopamine and (±)-o-synephrine by rats was studied quantitatively by a gas chromatography-mass spectrometry-selected ion monitoring (g.c.-m.s.-s.i.m.) method using deuterated internal standards. When o-octopamine was injected intraperitoneally into rats four metabolites were excreted in the urine: (i) unconjugated o-hydroxymandelic acid (OHMA) (16%), (ii) unconjugated o-hydroxyphenylglycol (OHPG) (4·5%), (iii) an acid-hydrolysable conjugate of OHPG (28%) and (iv) unconjugated o-octopamine (10%). When o-synephrine benzoate was similarly administered six metabolites were excreted in urine: (i) unconjugated OHMA (13·5%), (ii) unconjugated OHPG (3·3%), (iii) an acid-hydrolysable conjugate of OHPG (15·6%), (iv) unconjugated o-synephrine (10%), (v) an acid-hydrolysable conjugate of o-synephrine (8·5%) and (vi) unconjugated o-octopamine (0·3%). Adult rats normally excreted OHMA (1·0 μg day−1) but OHPG, o-octopamine and o-synephrine could not be detected in urine. After the administration of a monoamine oxidase inhibitor, unconjugated o-octopamine (0·3 μg day−1) was excreted in urine but OHPG and o-synephrine could not be detected. o-Tyramine given to rats afforded urinary o-octopamine (75 ng day−1) and this was increased 10-rold upon co-administration of a monoamine oxidase inhibitor and o-tyramine.
Comparison of digoxin-induced cardiac toxicity in resistant and sensitive species
Authors: Weinhouse Elliott , Kaplanski Jacob , Posner John 
Published: April 2011

Abstract
We have examined the species-specific arrhythmogenic effects of digoxin in the rat (resistant species) and in the guinea-pig (sensitive species). 26 adult rats and 23 adult guinea-pigs were anaesthetized with pentobarbitone and injected subcutaneously with varying doses of digoxin. Electrocardiograms were monitored continuously for 4 1/2 h following digoxin administration. The arrhythmogenic dose (AD50) and lethal dose 50 under anaesthesia (LD50) were determined using the method of Litchfield & Wilcoxin. AD50 in rats was 13·0 ± 1·0 mg kg−1 (mean ± s.d.) compared with 0·60 ± 0·04 (P &lt; 0·01) in the guinea-pig and LD50 was 30·0 ± 1·9 mg kg−1 in the rat compared with 0·60 ± 0·04 (P &lt; 0·01) in the guinea-pig. The onset of arrhythmias was not dose-dependent in the rat but was clearly so in the guinea-pig; for example 102 ± 15 min (mean ± s.e.m.) following 0·5 mg kg−1, and 43 ± 2 mm following 1 mg kg−1. In the rat the onset of arrhythmias was 54·0 ± 11·5 min. Supraventricular arrhythmias (paroxysmal atrial tachycardia) appeared in 73% of rats compared with only 18% of guinea-pigs whereas ventricular arrhythmias (ventricular tachycardia), multiple premature ventricular contractions and or multifocal PVC’s occurred in 100% of guinea-pigs compared with only 32% of rats. All guinea-pigs that developed arrhythmias died whereas several rats recovered from supraventricular tachycardias. In conclusion, the guinea-pig is much more sensitive to digoxin toxicity than the rat, develops arrhythmias at much lower doses and these arrhythmias are much more likely to be ventricular in origin and cause fatality.
Influence of drug partition coefficient and pH value of sink solution on permeation from porous thick-walled ethyl cellulose microcapsules
Authors: Vidmar Vesna , Jalšenjak I 
Published: April 2011

Abstract
The permeation of barbitone sodium, benzoic acid, and salicylic acid from microcapsules into aqueous medium has been examined at different pH values. The apparent diffusion coefficients of drugs were linearly proportional to the ethyl cellulose/water partition coefficient of drugs, and the straight line parameters were dependent upon volume fractions of water-filled pores (i.e. capsule size), testifying to a previously proposed mechanism of drug permeation. The rate of drug permeation was also a function of the pH-value of the surrounding sink solution; the period of zero order release was longer at low pH because of the change of drug partition or solubility or both.
Motor inhibition induced by aporphine derivatives in the mouse
Authors: Bradbury Amanda J , Costall Brenda , Naylor Robert J , Neumeyer John L 
Published: April 2011

Abstract
The ability of some aporphine and benzylisoquinoline derivatives to inhibit mouse spontaneous locomotor activity at low doses, and at higher doses to have a reduced motor inhibitory effect, was used to determine whether motor inhibitory and facilitatory potentials could be dissociated, and the optimal structure required to cause these behavioural changes. Ability to displace [3H]2-amino-6,7-dihydroxy-1,2,3,4-tetrahydro-naphthalene [3H]ADTN from its binding sites in rat striatal tissue was used as a broad measure of the abilities of the test compounds to bind to the ‘dopamine receptor’. The order of potency for ‘low dose’ inhibition of mouse spontaneous locomotion was (1) (-)N-n-propylnorapomorphine&gt;(2) apomorphine &gt; (3) (-)2,10,11-trihydroxy-N-n-propylnoraporphine &gt; (4) (-)2,10,11-trihydroxyaporphine &gt; (5) f-10,11-dihydroxy-N-(hydroxy-ethyl)noraporphine &gt; (6) norapomorphine &gt; (7) (±)10-hydroxy-N-n-propylnoraporphine &gt; (8) 1-(3,4-dihydroxybenzyl)-2-n-propyl-1,2,3,4-tetrahydroiso- quinoline. The latter two compounds were only weakly active and (±)8-hydroxy-N-n-propylnoraporphine and 1-(4-hydroxybenzyl)-2-n-propyl-1,2,3,4-tetrahydroisoquinoline were inactive. The reduction in motor inhibitory effect as dose of agonist was increased (indicative of facilitation of locomotion) was only observed with compounds 1 and 2, other compounds (3 and 4) caused non-specific changes which interfered with motor performance or the doses required were so large as to render testing impractical (5,6,7 and 8). The potent motor inhibitory actions of compounds 1–4 were antagonized by pretreatment with spiperone but not with prazosin or yohimbine. Specific binding of 2·0nM [3H]ADTN was displaced by nanomolar concentrations of (±)-ADTN and aporphine derivatives. Isoapomorphine and the two benzylisoquinoline derivatives were ineffective at 10−6M. The optimal structure for those derivatives examined was shown in all tests to be (-)N-n-propylnorapomorphine.
Differential inhibition of α2-adrenoceptor-mediated pressor responses by (+)- and (-)-verapamil in pithed rats
Authors: van Meel Jacques C A , Qian Jiaqing , Timmermans Pieter B M W M , van Zwieten Pieter A 
Published: April 2011

Abstract
The inhibitory effects of (+)- and (-)-verapamil on the hypertensive responses brought about by the α2-adrenoceptor agonist B-HT 920 were investigated in pithed normotensive rats. (-)-Verapamil was found to be about 4 times more potent with respect to depressing α2-pressor responses compared with (+)-verapamil. To rule out the effect of ‘unspecific’ vasodilatation after the administration of the stereoisomers of verapamil, vasopressin was continuously infused into the carotid artery of pithed rats in a separate series of experiments. In the course of this vasopressin infusion, new inhibitory activities of the stereoisomers of verapamil on α2–adrenoceptor-mediated pressor responses were determined. Under these circumstances, the potency ratio of (-)- vs (+)-verapamil was about 7. With the aid of a radioligand binding assay using [3H]clonidine to identify α2–adrenoceptors, low affinities were measured for the stereoisomers of verapamil. A Ki = 6170 nM for (-)-verapamil and a Ki = 41700 nM for (+)-verapamil were calculated. The results indicate that the interaction between α2-adrenoceptor-mediated pressor responses and calcium entry blockers, such as verapamil, is a stereoselective event.
Mechanism of inhibition of contraction by cadmium in guinea-pig taenia coli
Authors: Nasu T , Koshiba H , Mase K , Ishida Y 
Published: April 2011

Abstract
Further evidence about the mechanism of the inhibition of contractions caused by cadmium ions (Cd2+) in guinea-pig taenia coli has been sought. Cd2+ at a concentration of 0·5 mM completely inhibited the high-K (40 mM)-induced contraction within 3–5 min. Cd2+ did not shift the Ca2+-induced concentration-response curve to the right in Ca2+-free K+ depolarized muscle, although it reduced the Ca2+ response size. The K+-induced increase in tissue calcium content and 45Ca uptake determined by the lanthanum method was significantly reduced in the presence of Cd2+ (0·5 mM) and the contractions of the glycerolated taenia coli were inhibited with increasing Cd2+ (0·001–0·5 mM). Muscle strips, incubated in a medium containing 0·5 mM Cd2+, accumulated greater amounts of cadmium than within the extracellular space. It is suggested that the inhibitory action on tension produced by Cd2+ in taenia coli may result from the interference of calcium permeability at the cell membrane. There is the possibility that Cd2+ acts on the contractile system of the muscle.
Binding of [3H]mianserin to bovine serum albumin, human serum albumin and α1-acid glycoprotein
Authors: Shami M R , Skellern G G , Whiting B 
Published: April 2011

Abstract
Scatchard plots which were curvilinear with negative slopes were obtained when the binding of [3H]mianserin to bovine serum albumin (BSA), human serum albumin (HSA), defatted human serum albumin (D-HSA) and α1-acid glycoprotein (α1-AGP) was studied with equilibrium dialysis with constant protein concentrations and various ligand concentrations. Binding parameters were estimated graphically and with a non-linear least-squares computer program, assuming two classes of independent binding sites. α1-AGP had the highest binding affinity (K) and binding capacity (nK). The binding parameters, n and K were not independent of protein concentration when the BSA concentration was varied. Linear atypical Scatchard plots with positive slopes were obtained when the protein concentration was varied for BSA, HSA and D-HSA, at a fixed ligand concentration.
Inhibitory effect of captopril on renal responses to frusemide in sodium-restricted rats
Authors: Chiu P J S , Brown A D , Barnett A 
Published: April 2011

Abstract
Indomethacin (10 mg kg−1 orally) caused a moderate inhibition of the renal responses to frusemide (30 mg kg−1 orally) only in Na+-deficient rats, suggesting that renal prostaglandins (PG) are necessary for optimal effects of frusemide during Na+ restriction. Captopril (1, 3 and 10 mg kg−1 orally) also inhibited frusemide-induced diuresis and natriuresis in Na+-deficient rats; the large effect of captopril at 10 mg kg−1 was accompanied by arterial hypotension. In normal rats, captopril did not disturb blood pressure or affect the renal effects of frusemide. By comparison, minoxidil (10 and 20 mg kg−1 orally) caused hypotension and reduced the natriuretic effects of frusemide in both normal and low-Na+ states. Since circulating angiotensin II (AII) is a stimulus for PG synthesis during Na+ restriction, it is suggested that captopril may impair the renal responses to frusemide through hormonal and haemodynamic changes resulting from inhibition of A II formation.
The influence of agitation intensity, particle size and pH of dissolution fluid on the in-vitro release of drug from hard gelatin capsules
Authors: Newton J M , Muhammad N A H 
Published: April 2011

Abstract
The influence of agitation intensity on the in-vitro release of controlled particle size fractions of acetylsalicylic acid from hard gelatin capsules into buffered dissolution fluids has been investigated employing a dissolution technique. The value of T50 decreased as the stirring rate increased from 120 to 320 rev min−1 for all particle size fractions and pH values. A further increase in the stirring rate had a limited effect on the value of T50 and the changes were particle size dependent. The influence of the drug solubility, induced by changing the pH of the dissolution fluid, was decreased by increased agitation. When the capsules were filled at bulk densities above the maximum tapped bulk density, the value of T50 was increased, the extent of increase being greater the smaller the particle size of the drug. The kinetics of the solution process were influenced by agitation intensity and particle packing.
Non-enhancement of sodium cromoglycate intestinal absorption by quaternary ammonium ions. An effect of salt on ion-pair formation?
Authors: Schurgers N , De Blaey C J , Tomlinson E 
Published: April 2011

Abstract
Studies on the nature of rat small intestine perfusates indicate that this environment is thermodynamically unfavourable for the production of ion pairs between cromoglycate and alkylbenzyldimethylammonium ions. This is suggested as being the reason why, unlike previously found for ocular absorption of cromoglycate, these quaternary ammonium ions do not alter cromoglycate intestinal absorption.
Structure elucidation of protriptyline photoirradiation products
Authors: Jones G E , Sharples D 
Published: April 2011

Abstract
Three photoirradiation products of the tricyclic antidepressant protriptyline have been isolated by preparative tlc and identified as the 10,11-epoxide, 10-hydroxy and 10,11-dihydrodiol derivatives of protriptyline by tlc, uv and mass spectroscopy.
Ethanol- and isoprenaline-induced responses in pig parenchymal lung tissue
Authors: Goldie R G , Ellis G M , Paterson J W 
Published: April 2011

Abstract
Ethanol (8·7–34·8 mm; 0·5–0·20% v/v) had no significant effect on spontaneously developed tension in pig lung parenchyma strips, although higher cumulative concentrations caused relaxation (at 34·8–174 mm) and contraction (at 348–1392 mm). Ethanol-induced effects were not caused by activation of adrenoceptors or of cholinoceptors, since blockade of these receptors did not alter those effects. Single low concentrations of ethanol (8·7–34·8 mm) which can occur in-vivo in man, caused increases in the relaxant potency of isoprenaline in pig lung strips, although the sizes of these increases varied widely. In addition, ethanol-induced potentiation of isoprenaline was not concentration-related. This effect was not caused by inhibition of isoprenaline uptake since [3H]isoprenaline transport was found not to be significantly altered in the presence of ethanol (8·7–34·8 mm).
Possible role of prostaglandins in post-tetanic potentiation at the nerve-muscle junction in the longitudinal muscle strip of guinea-pig ileum
Authors: Kadlec Ondřej , Mašek Karel , Růžička Vladimir , Šeferna Isidor 
Published: April 2011

Abstract
The effect of tetanic stimulation on the twitch responses of the longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum to electrical stimulation was investigated in the presence of naloxone. Under this condition, or after the addition of PGE2, twitch contractions were maximal and no potentiation of twitches following tetanus was observed. In the presence of indomethacin (1 μmol litre−1) twitches were diminished and post-tetanic potentiation (PTP) was manifested. PTP was seen with indomethacin concentrations of 1 to 20 μmol litre−1 or after simultaneous addition of diphloretin phosphate (16 μmol litre−1). Thus it seems unlikely that the effect of prostaglandins released during tetanic stimulation would be of key importance for the manifestation of PTP. Rather it is thought that a decrease in the release of acetylcholine from motor nerve terminals, and consequently smaller twitches in the presence of indomethacin, offer favourable conditions for PTP.