bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of prostaglandins and clonidine in the rat vas deferens
Authors: Griffiths R J , Moore P K 
Published: April 2011

Abstract
Stimulation of presynaptic α2-adrenoceptors by clonidine may lead to local synthesis of prostaglandins which contribute to the inhibition of noradrenaline release observed with this drug. The present investigation was undertaken to determine the role of prostaglandins in the effect of clonidine and xylazine on the rat vas deferens. Both drugs inhibited the twitch response to field stimulation in this preparation. Inhibition was reversed by yohimbine. This effect of clonidine (but not xylazine) was reduced by preincubating vasa deferentia in Krebs containing indomethacin for 1h. Clonidine (but not xylazine) stimulated the synthesis of prostaglandin-like activity in pieces of intact vas deferens incubated in Krebs containing arachidonic acid. Such stimulation was prevented by inclusion of yohimbine (but not prazosin) in the incubation medium. Clonidine did not stimulate prostaglandin synthesis in a cell-free preparation of sheep seminal vesicle microsomes incubated with arachidonic acid or inhibit PGE2 catabolism by purified swine lung 15-PGDH. We conclude that clonidine (but not xylazine) stimulates prostaglandin synthesis possibly by activating phospholipase activity and releasing arachidonic acid from membrane phospholipids. This effect on prostaglandin production is secondary to activation of α2-adrenoceptors.
Solubility behaviour of griseofulvin in fatty acids
Authors: Grant D J W , Abougela I K A 
Published: April 2011

Abstract
The solubility of griseofulvin in the straight-chain alkanoic acids from C2 to C22 and in the C4 and C5 alkanoic acids branched at C-2 was measured at various temperatures. The enthalpy of fusion of griseofulvin, measured by differential scanning calorimetry, was 39.39 kJ mol−1 at the melting point (495.15 K) and 36.95 kJ mol−1 at 373.15 K. The standard Gibbs free energy (ΔG°), standard enthalpy (ΔH°) and standard entropy (ΔS°) of solution were calculated at 373.15 K, from the van't Hoff plot of the temperature dependence of the mole fraction solubility in terms of the pure supercooled liquid solute as the standard state. With increasing chain length of the alkanoic acid solvents, ΔG° increased in parallel with the increase in pKa of the acids in water, suggesting that the solubility behaviour involves specific solute-solvent proton interactions, while ΔH° and ΔS° fluctuated but tended to decrease in parallel with the corresponding decreases in their enthalpies and entropies of ionization, respectively. The fluctuations in ΔH° and ΔS° may be attributed to the different solid adducts containing griseofulvin and the solvent. An observed non-linear (logarithmic) decrease in solubility with decreasing molality of the carboxyl group in the liquid solvent on ascending the homologous series is attributed to the disturbing influence of the hydrocarbon chains on the specific solute-solvent hydrogen bonding. Chain-branching of the solvent at C-2 gave a reduced solubility of griseofulvin and higher ΔG°, ΔH° and ΔS° values compared with the corresponding straight chain acid.
Effects of cold stress and ether stress on aminopyrine demethylation kinetics in vivo
Authors: Lockwood G F , Houston J B 
Published: April 2011

Abstract
The effect of cold stress and ether stress on mixed function oxidase activity in vivo has been studied using the aminopyrine-−14CO2 exhalation rate (CER) method. Cold stress following both acute and chronic exposure resulted in enhanced rate of demethylation of both aminopyrine (CER α half-life) and its monomethyl metabolite (CER β half-life). However the time course of the response to cold stress differs for the two demethylations. The characteristics of the cold-induced enhancement of aminopyrine-CER would appear to differ in several aspects from that reported for phenobarbitone pretreatment. In contrast, ether exposure did not produce any consistent effect on drug metabolizing status of the rat.
Interactions of ionic and non-ionic surfactants with plasma low density lipoprotein
Authors: Tucker Ian G , Florence A T 
Published: April 2011

Abstract
Surfactants might be useful in facilitating the replacement of the interior of low density lipoprotein (LDL2) (ρ = 1˙02-1˙063 g ml−1) with drug molecules. We have used photon correlation spectroscopy, supported by sedimentation velocity measurements to study the effects of surfactants on LDL2. Sodium dodecyl sulphate, cetrimide, and all non-ionic surfactants studied caused rapid increases of ca 50% in the Stokes' radius up to surfactant/LDL2 molar ratios of ca 1000:1. This was interpreted as due to partial unfolding of the LDL2 protein and intercalation of surfactant with the LDL2 surface layer. At higher concentrations, ionic surfactants and non-ionics with HLB values &lt;14˙6 decreased the Stokes' radius due to delipidation of LDL2. These interactions are similar to those between surfactants and biological membranes, thus LDL2 might be a useful model system to study surfactant structure-activity relationships.
The refractive indices of polymer film formers, pigments and additives used in tablet film coating: their significance and practical application
Authors: Rowe R C , Forse S F 
Published: April 2011

Abstract
The refractive indices of both the polymer film formers and additives are a fundamental factor in defining the appearance of the subsequent film coatings. The refractive indices of the polymer film formers are all in the region of 1·5 but those of pigments and additives vary between 1·5-3·2. Most pigments and additives are also anisotropic, i.e. they possess different refractive indices depending on their orientation. These observations have implications in the use of pigments and additives for the production of both opaque films with good hiding power and film-coated tablets with highlighted intagliations.
Enterohepatic circulation of radioactivity following an oral dose of [14C]temazepam in the rat
Authors: Tse F L S , Ballard F , Jaffe J M , Schwarz H J 
Published: April 2011

Abstract
The enterohepatic circulation of radioactive material after administering [14C]temazepam was evaluated in three sets of male Wistar strain rats connected in pairs by bile duct-duodenum cannulae. After a single oral dose (10 mg kg−1) to the donor rat, the excretion of radioactivity in the urine and faeces of both rats and in the bile of the recipient rat was determined. Mean total recovery of the administered radioactivity was 92·2%. Based on the amount remaining in the donor rat (gastrointestinal tract and faeces), 81·7% of the dose was absorbed by the donor. The total amount recovered from the recipient, 69·4% of original dose (85·1% of donor’s absorbed dose), represented the amount excreted in the donor’s bile. Similarly, 54·1% of the original dose (77·9% of the transferred biliary excretion from donor) was reabsorbed by the recipient, and the biliary excretion from this animal (45·9% original dose) accounted for 86·% of the amount reabsorbed.
The effect of clonidine on the response to stimulation of non-adrenergic non-cholinergic nerves in the guinea-pig urinary bladder in-vitro
Authors: Muir T C , Smart N G 
Published: April 2011

Abstract
The effects of clonidine on the response of the guinea-pig urinary bladder detrusor muscle to stimulation of non-adrenergic non-cholinergic (NANC) nerves were investigated in-vitro. In tissues from both treated and chemically sympathectomized animals, in the presence of atropine (10−5 M) to inhibit cholinergic responses, clonidine (10−10-10−6 M) invariably enhanced the contractile response to NANC nerve stimulation at 2, 5, 10 and 20 Hz. The enhancement was not inhibited by yohimbine (10−5 M), phentolamine (10−5 M), or the histamine H1 or H2-receptor antagonists mepyramine (10−6 M) or cimetidine (10−5 M) respectively. Phentolamine (10−5 M), like clonidine, enhanced the response to stimulation of NANC nerves at 2, 5, 10 and 20 Hz. Xylazine, another α2-agonist, which, unlike both clonidine and phentolamine, is not a substituted 2-imidazoline compound, failed to enhance the response in the bladder to NANC nerve stimulation. The results suggest that clonidine enhances the response to NANC nerve stimulation, independently of its effects on α-adrenoceptors, by increasing the amount of NANC transmitter available.
Radioimmunoassay of the new opiate analgesics alfentanil and sufentanil. Preliminary pharmacokinetic profile in man
Authors: Michiels M , Hendriks R , Heykants J 
Published: April 2011

Abstract
The development of two analogous radioimmunoassay (RIA) procedures based on dextran-charcoal separation is described for the quantification of two fentanyl-like analgesics, alfentanil and sufentanil. Immunization of rabbits with conjugates of bovine serum albumin and carboxy-derivatives of the respective drugs resulted in the production of antisera capable of detecting less than 0.05 ng ml−1 of the parent analgesics with high specificity and almost no cross-reactivity with major metabolites. Excellent agreement was obtained between RIA—without prior extraction—and gas chromatography for alfentanil concentrations in human plasma. Because of sufentanil’s low therapeutic plasma levels, no comparison could be made between its RIA and an alternative assay, however, there was strong evidence for the specificity of the assay when applied directly to plasma. With these RIA methods preliminary information was obtained on plasma concentrations and elimination of alfentanil or sufentanil in patients given an intravenous bolus injection of 50 μg kg−1 of alfentanil, or 5 μg kg−1 of sufentanil. For both analgesics, the pharmacokinetic profile in man could be described by a three-compartment model. The terminal elimination half-life was 88 min for alfentanil and 140 min for sufentanil. Six hours after a therapeutic dose, plasma levels were in the order of 3 and 0.3 ng ml−1 for alfentanil and sufentanil respectively.
Inhibition of acetylcholine-stimulated secretion in the isolated whole stomach of the rat
Authors: Parsons M E , Price Carolyn , Wintermeyer Donna 
Published: April 2011

Abstract
The rat isolated whole stomach preparation has been used to investigate acetylcholine-stimulated pepsin secretion. Acetylcholine stimulated pepsin output in a dose dependent manner over the range 3 times 10−4 to 3 times 10−3 M. Metiamide (10−3 M) had no significant effect on the pepsin response to acetylcholine suggesting that histamine H2-receptors are not involved in this response. Atropine (2 times 10−8, 2 times 10−7 and 2 times 10−6 M) produced a dose-related inhibition of the pepsin output to 7 times 10−4 M acetylcholine, indicating that this response is mediated by muscarinic receptors. Pirenzepine also produced a dose-related inhibition of acetylcholine (7 times 10−4 M) stimulated pepsin output at 2 times 10−6, 2 times 10−5 and 2 times 10−4 M. Increasing the concentration of acetylcholine to 3 times 10−3 M completely reversed the effect of atropine (2 times 10−6 M) but pirenzepine (2 times 10−4 M) still produced a significant inhibition of acetylcholine-stimulated pepsin secretion. In each series of experiments acid and pepsin secretion responded in a similar manner to the effects of inhibitors, providing no evidence for a separation of these responses.
The mammalian metabolism of R-(-)-m-synephrine
Authors: Ibrahim Kamal E , Midgley John M , Crowley Jan R , Williams Clyde M 
Published: April 2011

Abstract
The metabolism of R-(-)-m-synephrine (administered orally and by inhalation in man and intraperitoneally in 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 m-synephrine hydrochloride was administered orally to humans in normal dosage regimens four main metabolites were excreted in urine: (i) unconjugated m-hydroxymandelic acid (MHMA, 30%), (ii) m-hydroxyphenylglycol (MHPG) sulphate (6%), (iii) m-synephrine sulphate (47%) and (iv) m-synephrine glucuronide (12%). The comparable figures after inhalation of the drug were 24, 6, 56 and 5%. Intraperitoneal injection of m-synephrine into rats gave: unconjugated MHMA (5%), MHPG sulphate (35%), unconjugated m-synephrine (7%) and conjugates of m-synephrine (9%:4% as the glucuronide and 5% as the sulphate).
Segregation of vibrated powder mixes containing different concentrations of fine potassium chloride and tablet excipients
Authors: Staniforth John N , Rees John E 
Published: April 2011

Abstract
The effect of different drug/excipient concentrations on the segregation tendency of three ordered powder mixes was studied. In addition, the influence of vibration frequency on the segregation intensity and mechanisms of segregation was also studied. Differences in content uniformity of the powders were measured by comparing samples from regions at different depths between the upper exposed powder surface and the base of the cylindrical container. Ordered mixes containing recrystallized lactose excipient and fine-particle potassium chloride as a model drug were found to be least susceptible to segregation at most vibration conditions for all potassium chloride concentrations. Dipac excipient/potassium chloride particles were most susceptible to segregation under all test conditions. In general, segregation intensity was most marked in conditions where high potassium chloride concentrations, above 2% w/w, were subjected to low-frequency vibration, below 100 Hz. Segregation mechanisms were considered to be mainly dependent on vibration conditions, although carrier excipient type markedly modified mechanisms and influenced segregation intensity.
Inhibition of sympathetic neurotransmission in the rat anococcygeus muscle by diazepam
Authors: Oriowo M A 
Published: April 2011

Abstract
In the rat anococcygeus muscle, diazepam (1·8 times 10−6 − 2·8 times 10−5 M), dipyridamole (2 times 10−6 − 3·2 times 10−5 M) and ATP (2 times 10−4 − 6·4 times 10−3 M) concentration-dependently inhibited the motor response to field stimulation. Glycine (up to 7·5 times 10−3 M) and GABA (up to 10−4 M) had no effect on field stimulation. Concentrations of diazepam and dipyridamole which reduced motor response to field stimulation did not relax the tonically contracted rat anococcygeus muscle. However, at these concentrations, diazepam and dipyridamole potentiated the inhibitory responses of the tonically contracted rat anococcygeus muscle to ATP and field stimulation. It is suggested that diazepam and dipyridamole reduced the motor response to field stimulation by potentiating the inhibitory transmitter released during nerve stimulation. Also, since the time-course of the effect of diazepam and dipyridamole on the inhibitory responses to ATP and field stimulation are closely similar, the results would tend to provide additional support for the concept of purinergic transmission in the rat anococcygeus muscle.
The ionization of β-adrenoceptor agonists: a method for unravelling ionization schemes
Authors: Ijzerman A P , Bultsma T , Timmerman H , Zaagsma J 
Published: April 2011

Abstract
To investigate the ionization schemes of β-adrenoceptor agonists, a combined electrochemical/uv-spectrophotometric method with computer-assisted data-analysis was developed, yielding the macroscopic and microscopic ionization constants. From the four species possible, cations and zwitterions were found the main species present at physiological pH, the formation of uncharged molecules and anions being less favourable or apparently negligible.
Counter-ion binding to mucus glycoproteins
Authors: Crowther Roger S , Marriott Christopher 
Published: April 2011

Abstract
The affinity of pig gastric mucus glycoprotein for counter ions of various valencies was examined. Ions of higher valency were bound with increasing avidity, but the degree of binding was apparently not influenced by the ionic radius. The affinity of the glycoprotein for the ions studied may be ranked: Fe3+ &gt; Al3+ &gt; Ca2+ &gt; Cs+ ≃ Na+. The binding of calcium was inhibited by high ionic strength and was sensitive to the pH of the environment. Enzymatic removal of sialic acid slightly reduced the calcium binding capacity.
Effect of sulfhydryl group modification on the neurotoxic action of a sea snake toxin
Authors: Ishizaki Hiroyuki , Allen Matthew , Tu Anthony T 
Published: April 2011

Abstract
Pelamis toxin a is a major neurotoxin isolated from the venom of Pelamis platurus (yellow-bellied sea snake). The effect of sulfhydryl group modification by NN’-1,4-phenylenedimaleimide on the neurotoxic action of Pelamis toxin a has been investigated. The cross-linked toxin having a molecular weight of 11 000 was formed without significant structural changes in the toxin. Lethality tests on the modified toxin indicated that it retained considerable toxicity, although its potency was weaker than that of the native toxin. Binding studies with the acetylcholine receptor isolated from the electroplax of Torpedo californica indicated that the modified toxin binds to the receptor but less effectively than the native toxin. These results suggest that the decreases in toxicity and binding to the receptor are due to a decrease in accessibility of cross-linked neurotoxin to the receptor. This leads us to the conclusion that the region of the neurotoxin containing the sulfhydryl group is not essential for its biological activity. Analysis of the structure and function relationships of the modified toxin suggests that the neurotoxin-acetylcholine receptor interaction requires the proper orientation of the neurotoxin molecule.
Biochemical effects of minaprine on striatal dopaminergic neurons in rats
Authors: Ferretti P , Algeri S , Benfenati F , Cimino M , Ferretti C , Garattini S , Lipartiti M 
Published: April 2011

Abstract
The biochemical effects of minaprine, a new psychotropic drug, were investigated on striatal dopaminergic neurons in the rat. Minaprine did not displace [3H]spiperone in-vitro binding from striatal membranes but had clear effects on dopamine (DA) metabolites. Homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly decreased in a dose-dependent manner after intraperitoneal administration of minaprine 30 min before killing. In rats injected with minaprine 15 mg kg−1 i.p. at different intervals, the decrease in striatal HVA and DOPAC was time-dependent and a concomitant rise in 3-methoxytryramine (3-MT) concentrations was observed. The maximum of these effects was reached 30 min after minaprine. When administered 5 min after a monoamineoxidase (MAO) inhibitor (pargyline, 100 mg kg−1 i.p.) and 30 min before killing, minaprine did not affect pargyline-induced changes in HVA, DOPAC and 3-MT levels. This together with other data suggests that minaprine affects DA metabolism by acting, at least partially, at presynaptic level through in-vivo inhibition of MAO activity.
An in-vitro investigation of mucosa-adhesive materials for use in controlled drug delivery
Authors: Smart J D , Kellaway I W , Worthington H E C 
Published: April 2011

Abstract
An in-vitro test system was developed to investigate the adhesiveness of various materials to mucus. The results obtained showed good agreement with the findings of previous in-vivo evaluations of mucosa-adhesives. Further investigations found that these materials become adhesive on hydration. Chain length, and the presence of ionizable groups in the molecule, were found to be determinate factors. The physical nature of the gel, and the location at which the mucoadhesive materials hydrated, were of less importance.
New simulators in the prophylaxis against soman poisoning: structural specificity for the depot site(s)
Authors: Van Helden Herman P M , Benschop Henk P , Wolthuis Otto L 
Published: April 2011

Abstract
The oxime HI−6 is effective as an antidote in the soman poisoned (6–8LD50) rat, however, successfully treated animals subsequently show a gradual relapse of signs of poisoning and eventually die after several hours. The relapse is caused by the reappearance of soman at specific sites, after having been elsewhere in the body. Diaphragms isolated from poisoned rats successfully treated with HI−6 also showed a ‘secondary’ relapse of poisoning. Eight compounds chemically related to soman-soman-simulators–-have been tested as prophylactic agents, for their potency in preventing the reappearance of poisoning. The idea was that such compounds may block the non-synaptic binding sites for soman. Three of the 8 compounds proved very effective, which gave some insight into the chemical structure needed for this type of prophylactic action.
Evidence that a novel dopamine receptor agonist, RDS-127 [2−di-n-propylamino−4,7−dimethoxyindane] has some centrally mediated cardiovascular actions
Authors: Arnerić Stephen P , Long John P 
Published: April 2011

Abstract
The cardiovascular effects of RDS−127 [2−di-n-propylamino−4,7−dimethoxyindane] were examined in normotensive, anaesthetized rats. RDS−127 given i.v. (12·5–125 μ kg−1) produced dose-dependent bradycardia. The bradycardic effect was 20·5 times more potent when the drug was administered intracerebroventricularly (i.c.v.) than when given i.v. RDS−127 produced a slight, but significant hypotension. Haloperidol given i.c.v. or i.v. reversed these bradycardic and hypotensive actions, whereas phentolamine was ineffective. Methylatropine partially reduced the bradycardic effect. These results suggest that RDS−127 activates central DA receptors to produce hypotension and bradycardia in rats.
The peripheral narcotic antagonist N-allyl levallorphan-bromide (CM 32191) selectively prevents morphine antipropulsive action and buprenorphine in-vivo binding in the rat intestine
Authors: Bianchi G , Fiocchi R , Peracchia F , Petrillo P , Tavani A , Manara L 
Published: April 2011

Abstract
The assumed low ability of the the quaternary narcotic antagonist N-allyl levallorphanbromide (CM 32191) to cross the blood-brain barrier and its selectivity in relieving the peripherally-elicited antipropulsive action of morphine while preserving analgesia has been tested. To ascertain the extent of penetration of CM 32191 into the cns, its relative potency in preventing the in-vivo binding of high specific activity [3H]buprenorphine in the rat cns and small intestine was compared. Pretreatment was with CM 32191 at 16, 30 or 60 mg kg−1 s.c., 20, 60 or 120 min before buprenorphine, the concentrations of which in cerebrum and spinal cord were comparable with control values, but were consistently reduced in the intestine (longitudinal muscle with attached myenteric plexus). Pretreatment with naloxone (20 min, 0·5 or 1 mg kg−1 s.c.) lowered buprenorphine binding in intestine and cns. Neither narcotic antagonist produced significant changes in buprenorphine plasma concentrations. The peripheral selectivity of CM 32191, methyl naloxone and naloxone was examined by investigating in the same rats nociception in the hot plate (central opiate-sensitive mechanism) and the transit of a charcoal meal along the small intestine (local opiate-sensitive mechanism). Both effects were inhibited by morphine (5 mg kg−1 i.v.). Naloxone (10 min pretreatment, 0·5 or 1 mg kg−1 s.c.) did not selectively antagonize intestinal action of the morphine since the relief of charcoal transit inhibition was consistently associated with complete loss of analgesia. Pretreament (s.c. at 50 min) with the N-methyl quaternary analogue of naloxone, at low doses only, selectively prevented the slowing of transit by morphine without significantly impairing its antinociceptive action; higher doses (&gt;16 mg kg−1) suppressed the antinociceptive action. In contrast, CM 32191 (16, 30 or 60 mg kg−1, 10, 50 or 110 min before morphine) always selectively antagonized constipation induced by the opiate and did not influence its action delaying hot-plate reaction.