bluuebunny/crossref_metadata_2025 huggingface dataset:
Stereospecificity of behavioural effects of viloxazine in bulbectomized rats does not correlate with its 5-HT-releasing action in vitro
Authors: GREENWOOD D T , KEMP JANET D , MIDDLEMISS D N
Published: April 2011

The effects of the antidepressant drug viloxazine and its two optically active isomers on the passive avoidance learning deficit surgically induced in rats by bilateral bulbectomy have been determined. Fourteen consecutive daily injections of either the racemate or the S-isomer (2, 5 and 10 mg kg−1 i.p.) significantly improved the acquisition of avoidance behaviour. The R-isomer was devoid of such activity in this same dose range. The various isomeric species of viloxazine were also studied in vitro for their ability to induce a release of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) from rat brain slices. In agreement with previous reports, racemic viloxazine caused a concentration-dependent (10−5 − 10−3 M> release of 5-HT without affecting any significant change in the release of either catecholamine. However, in contrast to the results of the behavioural studies, this phenomenon did not exhibit stereospecificity, all three isomeric forms being equally active. Thus, there is no simple relationship between viloxazine's behavioural activity in bulbectomized rats and its 5-HT releasing properties observed in vitro. The significance of these findings with respect to previously reported effects of the drug indicative of facilitation of central 5-HT mediated processes is discussed.
Effects of cyclodextrins on the acid hydrolysis of digoxin
Authors: UEKAMA K , FUJINAGA T , HIRAYAMA F , OTAGIRI M , KURONO Y , IKEDA K
Published: April 2011

The effects of three cyclodextrins (α-, β-, γ-CyD) on the acid hydrolysis of digoxin were examined. From the high performance liquid chromatographic tracing of each of the four components (digoxin, bisdigitoxoside, monodigitoxoside, digoxigenin) in reaction mixtures, the individual rate constants (k1-k6) were determined by analogue computer simulation. The hydrolysis was suppressed by CyDs in the order of β->γ->α-CyD, where β-CyD inhibited the appearance rates of digoxigenin (k3, k5, and k6) significantly. In the dissolution study of digoxin tablets, the increase in dissolution rate and decrease in acid hydrolysis were attained by inclusion complexation. The data are presented suggesting that CyDs are useful for improving the oral bioavailability of digoxin.
Are the prejunctional histamine receptors on sympathetic nerve terminals in guinea-pig isolated atria activated during anaphylaxis in vitro?
Authors: WONG-DUSTING H , STORY D F , RAND M J
Published: April 2011

In isolated atria from sensitized guinea-pigs, antigenic challenge with ovalbumin induces an anaphylactic reaction in which there is an increased rate and force of contraction. At the same time, stimulation-induced release of [3H]noradrenaline is inhibited by 40%. Cimetidine decreased the tachycardia occurring during anaphylaxis but had no effect on the inhibition of stimulation-induced transmitter release. It is known that antigenic challenge of sensitized guinea-pig atria releases histamine from mast cells; this histamine acts postjunctionally to increase heart rate. However, the inhibition of noradrenergic transmitter release is not due to the stimulation of prejunctional inhibitory histamine receptors.
Practical implications of theoretical consideration of capsule filling by the dosator nozzle system
Authors: JOLLIFFE I G , NEWTON J M
Published: April 2011

Eight lactose size fractions with mean particle sizes ranging from 15.6 to 155.2 μm were characterized by their failure properties using a Jenike shear cell. The effective angle of internal friction was found to be constant for all size fractions, with a mean value of 36.2°. Jenike flow factors could only be obtained for the two most cohesive size fractions presumably due to limitations of the shear cell. Angles of wall friction, ϕ, were determined for all size fractions on face ground and turned stainless steel surfaces. These decreased with increasing particle size up to around 40 μm, above which they became effectively constant for both surfaces. The rougher turned plate gave consistently higher values of ϕ for each particle size. Simple retention experiments with a dosator nozzle and a range of powder bed bulk densities showed good retention was possible only up to a particle size of around 40 μm. Retention was difficult or impossible above this size. Values of ϕ were applied to equations derived in the theoretical approach described previously (Jolliffe et al 1980). This showed that the strength required within a powder to ensure arching increases with increasing particle size up to around 40 μm. Above this size, this strength requirement becomes constant. This is related to the powder retention observations. Finally, the failure data was used to calculate the minimum compressive stresses required to ensure powder retention within the dosator nozzle, by employing the equations described by Jollife et al (1980). This suggested that, as powders became more free flowing, a larger compressive stress is necessary and that the angle of wall friction should be lower to ensure stress is transmitted to the arching zone.
Incidence of experimental cirrhosis on hepatic disposition of [3H] levamisole in rats
Authors: GALTIER P , COCHE Y , CAMGUILHEM R
Published: April 2011

Levamisole [phenyl-2 3H] was injected intravenously (4.7 mg kg−1) into anaesthetized controls and rats in which cirrhosis had been induced by a combination of carbon tetrachloride and phenobarbitone. The biliary excretion (6 h) of the parent drug and its metabolites formed a significant part of the administered dose. Although bile flow did not vary, biliary excretion of levamisole and metabolites were respectively increased and decreased in cirrhotic compared with control animals. These differences could be the result of cirrhosis-induced decrease in the hepatic biotransformation of levamisole and also to limited active carrier transport for the output of metabolites into bile canaliculi.
Catecholamine-induced relaxation and contraction of the lower oesophageal and pyloric sphincters of guinea-pig stomach: modification by domperidone
Authors: SAHYOUN H A , COSTALL B , NAYLOR R J
Published: April 2011

Catecholamine control of circular smooth muscle activity of the lower oesophageal (LOS) and pyloric sphincters (PS) of the guinea-pig was studied using α- and β-adrenoceptor agonists and antagonists. In both sphincters dopamine (DA) and noradrenaline (NA) caused relaxation followed by contraction of the circular smooth muscle, although the ability of NA to contract the PS was weak and inconsistent. Isoprenaline relaxed both sphincter preparations but, whilst phenylephrine contracted the muscle of the PS, it caused a biphasic relaxation-contraction of the LOS. The use of the α- and β-adrenoceptor antagonists, phentolamine and propranolol, indicated that contractions of both sphincters by NA and DA involved an α-type adrenoceptor whilst relaxation was mediated via a β-adrenoceptor (PS) or via both α- and β-adrenoceptors (LOS). Use of the α1 and α2 antagonists, prazosin and yohimbine, indicated that the α-adrenoceptor type involved with both the contractions and relaxation was α1. Both domperidone and haloperidol antagonized the contractile responses of both tissues to DA (and partly the relaxation of the LOS) but were similarly effective against the contractions induced by NA and phenylephrine; an effect on α1-adrenoceptors was therefore concluded. In selectively antagonizing the contractile effects of DA in the PS, domperidone enhanced DA's ability to relax this sphincter.
Effect of particle size on the compaction mechanism and tensile strength of tablets
Authors: MCKENNA A , MCCAFFERTY D F
Published: April 2011

The effect of particle size variation on tablet tensile strength for spray-dried lactose, Sta-Rx 1500 and Avicel PH-101 was investigated. Decreasing the particle size of spray-dried lactose and Sta-Rx 1500 resulted in stronger compacts whereas the tablet tensile strength of Avicel PH-101 was unaffected by particle size variation. The Heckel relationship, at two different contact times, was used to examine the predominant compaction mechanism. This was independent of the size fractions studied for all three materials. Angle of repose and Hausner ratio measurements indicated a correlation between the internal forces of friction and cohesion of the sized powders and the tensile strength of compacts formed from them.
Effect of reserpinization on insulin secretion in the rat
Authors: KAWADA TSUTOMU , ITAYA KOICHI
Published: April 2011

Reserpine-induced supersensitivity to the insulin-releasing action of a β-adrenergic agonist, isoprenaline, and of glucose was studied in vivo and in vitro. The subcutaneous injection of rats with reserpine (0.05 to 10 mg kg−1) enhanced the action of isoprenaline on insulin secretion. ED50 of isoprenaline for insulin secretion was changed little after reserpinization, whereas maximum effect of the β-agonist was enhanced by pretreating rats with reserpine. Glucose-stimulated insulin secretion was also enhanced in the reserpinized rats. Pancreases isolated from the reserpinized rats secreted more insulin in response to phentolamine in the presence of glucose and isoprenaline. These results suggest that the supersensitivity in insulin secretion induced by reserpine may be non-specific.
Catecholamines act at α2-adrenoceptors to cause contraction of circular smooth muscle of guinea-pig stomach
Authors: SAHYOUN H A , COSTALL B , NAYLOR R J
Published: April 2011

Circular smooth muscle strips taken from the body region of the guinea-pig stomach responded to dopamine and noradrenaline with contraction at lower concentrations followed by relaxation at higher concentrations. A (β-adrenoceptor-mediated relaxation response was excluded by propranolol treatment and this allowed the remaining α-adrenoceptor involvement with relaxation and contraction to be incisively differentiated in terms of two distinct α-adrenoceptor mechanisms. Thus, the relaxation responses to the catecholamines were mimicked by phenylephrine and antagonized by prazosin, phentolamine but not by yohimbine or rauwolscine. In contrast, the catecholamine-induced contractions were mimicked by clonidine and antagonized by yohimbine and phentolamine but not by prazosin. It is therefore concluded that the α mechanisms via which dopamine and noradrenaline are able to relax and contract the circular smooth muscle from the body region of guinea-pig stomach are of the α1- and α2-type respectively.
Stabilization of water/oil/water multiple emulsions by polymerization of the aqueous phases
Authors: Florence A T , Whitehill D
Published: April 2011

In order to improve the stability of w/o/w multiple emulsions which have isopropyl myristate as the non-aqueous ‘oil’ phase, either the internal aqueous phase of the multiple system or the secondary (outer or continuous) aqueous phase can be gelled. Production, by γ-irradiation, or cross-linked polyacrylamide or poloxamer gels in the aqueous phases of the emulsions leads to systems which have a greater intrinsic stability than untreated multiple emulsions. If the internal aqueous phase is gelled this prevents coalescence. When the continuous outer phase is gelled an opaque emulsion is produced in which the disperse w/o droplets are held in a hydrophilic polymer network from which the droplets are released on contact with water.
Effect of vibration time, frequency and acceleration on drug content uniformity
Authors: Staniforth John N , Rees John E
Published: April 2011

The effect of different vibration conditions on the segregation tendency of three ordered powder mixes was studied. Segregation of the powders was measured using a cylinder, composed of interlocking units for sampling purposes, mounted on a vibration rig. Ordered mixes containing either Emdex or recrystallized lactose carrier particles mixed with 0.5% fine-particle potassium chloride were stable, except for slight segregation that occurred under severe vibration conditions at frequencies below 50 Hz and accelerations above 22 m s−2. Powder mixes of Dipac with potassium chloride were unstable at most vibration conditions from 20 to 1000 Hz and 7.4 to 29.4 m s−2. The intensity of segregation in vibrated mixes of Dipac with potassium chloride was most marked at frequencies below 50 Hz and accelerations above 22 m s−2. These vibration conditions were found to occur in several commonly-used types of tableting presses. When vibration was prolonged, for periods of 30 to 60 min, there was increased segregation found in ordered mixes.
The effect of oils on the lymphatic absorption of DDT
Authors: Palin K J , Wilson C G , Davis S S , Phillips A J
Published: April 2011

Plasma concentrations of DDT were measured in conscious rats following oral administration in arachis oil, Miglyol 812 (fractionated coconut oil), liquid paraffin or as a fine suspension in water. The total absorption of DDT, calculated as the area under the plasma concentration time curve, was significantly greater for the arachis oil formulation compared to the other vehicles. In anaesthetized rats it was shown that DDT absorption was almost totally via the lymphatic system, and that lymph levels of DDT were highest following administration in arachis oil. Measurement of lymph flow showed that this enhanced absorption of DDT in the presence of arachis oil was not due to an increased flow as both arachis oil and liquid paraffin stimulated lymph production to the same extent.
Transamination and other metabolic pathways of 3,4-dihydroxyphenylpyruvic acid in rats when simultaneously administered with L-dopa
Authors: LindéN I-B , Karlsson M , Niemi S , Penttilä A
Published: April 2011

In the rat, 3,4-dihydroxyphenylpyruvic acid (DHPPA) was shown to be transaminated to L-dopa when administered orally concomitantly with L-[3H]dopa. As much as 40% of the serum L-dopa and brain dopamine was shown to be formed via transamination. Moreover, it was shown that DHPPA also caused a so-called L-dopa-sparing effect, i.e. more administered L-dopa reached the circulation and consequently more dopamine reached its target than after administration of L-dopa alone. This effect might be due to an inhibition of the deamination of L-[3H]dopa, since in this case the equilibrium of the transamination reaction will be forced into the L-dopa-forming direction. After administration of [14C]DHPPA alone and together with L-dopa, no differences in the absorption and distribution of radioactivity were found.
An evaluation of starch obtained from plantain Musa paradisiaca as a binder and disintegrant for compressed tablets
Authors: Esezobo S , Ambujam V
Published: April 2011

The binding and disintegrant properties of plantain starch obtained from Musa paradisiaca, family Musaceae, have been evaluated. Its effect in tablets of paracetamol and chloroquine phosphate on their physical properties such as hardness, friability and disintegration time was compared with tablets prepared with maize starch. The results show that plantain starch can be used both as a tablet binder and disintegrant in the preparation of tablets and the indication is that plantain starch has about twice the binding efficiency and about half the disintegrant power of maize starch.
Gas chromatographic determination of pargyline and pargyline amine metabolites after derivatization with isobutyl chloroformate
Authors: Weli Afaf M , Ahnfelt Nils-Otto , Lindeke BjöRn
Published: April 2011

Pargyline (I) and four of its major amine metabolites, N-benzylpropargylamine (II), N-methylpropargylamine (IV), N-benzylmethylamine (VI) and pargyline N-oxide (VIII), were determined by g.l.c. after reaction with isobutyl chloroformate in a two-phase system. Pargyline and metabolite IV which form the same derivative, were separated quantitatively by liquid-liquid distribution before derivatization with isobutyl chloroformate. Also, metabolites VI and VIII form identical derivatives, and as they could not be easily separated, VIII was reduced to I before derivatization. The analytical method was applied in studies of the metabolism of pargyline in microsomes from phenobarbitone pretreated rats. The metabolism was rapid, leading mainly to the formation of II, IV, VI and VIII. 92% of the substrate was consumed during the first min of incubation at an initial substrate concentration of 100 μM (32 nmol mg−1 protein), and II, IV, VI and VIII accounted for 83% of formed metabolites. The metabolite II was further metabolized while the levels of IV, VI and VIII remained constant after 5 min. It was possible to determine 0.5 μM of pargyline, II and VI in microsomal incubations, with an r.s.d. of <5% (n = 6). N-Methylpropargylamine (IV) was positively identified and quantitated as a pargyline metabolite for the first time.
Effects on tracheal smooth muscle of adenosine and methylxanthines, and their interaction
Authors: Karlsson J-A , Kjellin G , Persson C G A
Published: April 2011

The relaxant effects of xanthine and 15 different methylxanthines were studied in a guinea-pig isolated tracheal ring preparation. Substitution in the 3- and 1-positions of the xanthine molecule were found to be of greatest importance for improving tracheal relaxant potency. The unsubstituted xanthine and all 9-methylated xanthines were weakly active. Adenosine occasionally contracted (slightly) the tracheae but a concentration-dependent relaxation was always recorded. Endogenous adenosine did not seem to contribute to the tracheal tone. Xanthines methylated in the 1-position consistently antagonized the relaxant effect of adenosine and produced graded rightward shifts of the concentration-response line to adenosine (competitive antagonism). Xanthines with an unsubstituted 1-position or with comethylation in the 9-position were generally without antagonism. The results support our view that bronchodilating xanthine derivatives lacking universal adenosine antagonism can be produced.
Morphine intake from poppy seed food
Authors: Bjerver Kjell , Jonsson John , Nilsson Anna , Schuberth Jan , Schuberth Jutta
Published: April 2011

Morphine was determined in commercially available poppy seed and seed cake as well as in urine from healthy normal human adults 3 and 15 h after ingestion of poppy seed cake. The following morphine concentrations were determined: between 374 ±51 and 9.4 ± 1.0 μmol kg−1 poppy seed of different brands, 290 ± 11 μmol kg−1 poppy seed paste, 1.43 ± 0.07 and 0.53 ± 0.15 μmol litre−1 urine sampled 3 and 15 h, respectively, after ingestion of two cakes and 0.67 ± 0.17 and 0.30 ± 0.06 μmol litre−1 urine sampled 3 and 15 h, respectively, after ingestion of one cake. It is concluded that a positive finding of morphine in the urine from a person suspected of heroin abuse calls on some attention due to possible accidental morphine intake from poppy seed food.
Compressional characteristics of four starches
Authors: Paronen P , Juslin M
Published: April 2011

Compression data about barley, corn, potato and wheat starches were obtained by two methods: the ejected tablet method and the tablet-in-die-method. These data were analysed using the Heckel and the Cooper-Eaton equations. The Heckel equation appeared to be the more sensitive in distinguishing the various stages during the compression. Die filling and rearrangement processes for the starches were especially dependent on particle size and shape and thus on contact area between particles. Densification of large starch particles (potato starch) owed more to die filling and less to rearrangement. Densification of small particles (corn starch) was the reverse. Starch having a wide particle size distribution (wheat) or an irregular particle shape (barley) underwent a relatively small amount of densification as a result of die filling and a relatively great amount of densification because of rearrangement of particles during tableting. The tendency of the starches to total and pure plastic deformation was dependent on particle size, size distribution and particle shape. Corn starch was the most prone to plastic flow with only little elastic recovery. Potato starch also flowed plastically with ease. Barley and wheat starches were the more elastic.
Intestinal contribution to the presystemic elimination of β-phenethylamine in the rat
Authors: Worland P J , Ilett K F
Published: April 2011

The metabolism of β-phenethylamine (PEA) has been investigated in intestinal, liver and lung homogenates from the rat. Metabolic activity was ranked liver << lung << duodenum < jejunum < ileum < colon. Absorption and metabolism of PEA was also studied using in-situ intestinal loops from rats. Absorption of PEA appeared to be a passively mediated process with metabolism occuring in the jejunum, ileum and colon. When isolated loops of jejunum were used, phenylacetic acid was the only metabolite formed. Presystemic elimination of PEA in anaesthetized rats, was largely attributable to the intestine and lung with a relatively small hepatic contribution.
Digoxin-specific antibody fragments and a calcium antagonist for reversal of digoxin-induced mesenteric vasoconstriction
Authors: Hess T , Scholtysik G , Salzmann R , Riesen W
Published: April 2011

The effect of digoxin-specific antibody fragments on glycoside-induced mesenteric vasoconstriction were investigated. Digoxin caused a sustained contraction of strips of isolated feline mesenteric artery lasting for several hours, while in anaesthetized cats it produced a significant decrease in blood flow and increase in resistance in the mesenteric artery. In-vitro, digoxin’s contractile effect was inhibited by ‘prophylactic’ addition of antibody to the organ bath, but the clinical use for prophylaxis is not a practical proposition. When the antibodies were added with the contraction of the arterial strip in response to digoxin already established, the tone of the preparation decreased significantly over 3 h, but the effect of the glycoside was not fully reversible. In-vivo, control animals not treated with antibodies developed arrhythmias, mesenteric blood flow fell by more than 50% and resistance increased by more than 80% relative to the initial values. These animals died of ventricular fibrillation before the end of the experiment. Animals treated with digoxin-specific antibody fragments after receiving digoxin injections showed no further decrease in mesenteric blood flow and 90 min after the last dose of digoxin, the flow was recovering and mesenteric resistance decreasing. Furthermore, all the animals that had received antibodies remained in sinus rhythm to the end of the experiment. In view of the latent period to onset of action of the antibodies, valuable time may be lost in impaired mesenteric blood flow. To bridge the gap or, indeed, as primary treatment, calcium antagonists merit consideration; in our experiments mesenteric vasoconstriction was abolished within a few minutes by application of the dihydropyridine calcium antagonist 4-(2,1,3-benzo-oxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic aid, diethyl ester (PY 108–068).
Mechanisms of antibacterial formaldehyde delivery from noxythiolin and other ‘masked-formaldehyde’ compounds
Authors: Gidley Michael J , Sanders Jeremy K M
Published: April 2011

Formaldehyde release in aqueous solutions of noxythiolin (N-methyl-N'-hydroxymethyl thiourea) has been monitored by nuclear magnetic resonance (n.m.r.) spectroscopy. The results suggest that antibacterial activity in such solutions resides mainly in the free formaldehyde. N.m.r. spectroscopy also demonstrated slow C-N bond rotation in noxythiolin and N-methylthiourea, with ΔG‡ of ca 15 kcal mol−1 (63 kJ mol−1)-N-Hydroxymethyl imidazole is marginally more effective than corresponding hydrated formaldehyde solutions, an effect which is attributed to more rapid turnover of unhydrated formaldehyde as detected by saturation transfer n.m.r. spectroscopy. These observations are combined with the known delivery of lethal iminium ions, R2N+=CH2, by compounds of the form R2NCH2X (X = OH, NR2; R is alkyl) to suggest a single consistent explanation of the antibacterial properties of a wide range of masked formaldehyde compounds.
Impairment of drug metabolism by the liver in experimental fascioliasis in the rat
Authors: Galtier P , Battaglia A , More J , Franc M
Published: April 2011

Fascioliasis has been produced in the rat by an oral administration of 20 metacercariae of Fasciola hepatica. Hepatic microsomal cytochrome P450 and b5 contents and both aminopyrine demethylase and aniline hydroxylase activities have been measured during the course of the experimental distomiasis. The cytochrome P450 concentration and microsomal drug metabolizing enzymes generally fell by weeks 3 to 8 post-infestation and recovered to normal values thereafter. For the same period, both the histoenzymatically assayed liver cytochrome oxidase and arylsulphatase activities were reduced whereas there were correlated increases in glutamic pyruvic and glutamic oxaloacetic plasma transaminases. Tissue inflammation and destruction provoked by young histophagous migrating flukes could be responsible for these changes that have already been observed in several hepatic diseases. The possible influence of naturally-induced fasciolasis on liver drug metabolism is discussed.
A monoamine oxidase-B inhibitor, MD 780236, metabolized essentially by the A form of the enzyme in the rat
Authors: Benedetti Margherita Strolin , Dow James
Published: April 2011

In-vivo studies on the metabolism of [14C]MD 780236 a short-acting selective type B MAO inhibitor in the rat showed the acid to be the major metabolite in plasma and urine, whereas it was minor in brain, where the alcohol was the major metabolite. Pretreatment with SKF 525-A did not modify the metabolite profile in brain, but benserazide decreased the alcohol. Pretreatment with (-)-selegiline had no effect, but clorgyline or clorgyline with (-)-selegiline significantly decreased the alcohol and increased the primary amine metabolite in brain. In-vivo results suggest that MAO-A is the enzyme responsible for the metabolism of MD 780236. This was confirmed by in-vitro studies. Rat brain homogenates extensively metabolized the drug, with the aldehyde being the major metabolite formed (28% of the total radioactivity in the incubation mixture after 60 min incubation). The acid (12%) was more important than the alcohol (4%) in-vitro. The addition of all metabolites originating from possible MAO activity gave 46% when the incubation was carried out at pH 7·4 and 82% at pH 8·8. The presence of NADPH or NAD+ did not alter the relative amounts of metabolites formed. Total metabolites originating from MAO activity in the presence of (-)-selegiline accounted for 40% of total radioactivity, whereas in the presence of clorgyline they accounted for 8% and in the presence of both clorgyline and (-)-selegiline they were reduced to 3%, compared with 45% in controls. As a further proof of the importance of MAO-A in the metabolism of MD 780236, rats were pretreated with clorgyline 1 h before the drug and MAO-B inhibition measured at different times ex-vivo in brain and liver. The short-lasting phase of inhibition of MAO-B disappeared after pretreatment with clorgyline, and inhibition at 24 h was as high as that at 1 h. These results demonstrate the importance of the A form of MAO for the metabolism of MD 780236.
Stability and functional properties of haemoglobin freeze-dried in the presence of four protective substances after prolonged storage: dose-effect relationships
Authors: Labrude Pierre , Vigneron Claude
Published: April 2011

Freeze-dried haemoglobin samples protected during the desiccation by sucrose, arginine aspartate, lysine aspartate, sodium-zinc EDTA and Ficoll 70 have been stored under air at 4 †C for 15 months. The analysis showed that sufficient concentrations of sucrose and of the amino-acid salts prevent the oxidation of haemoglobin and maintain its functional properties. Relationships between the concentrations of these compounds and the methaemoglobin levels before and after storage were calculated. They define theoretical concentration points where methaemoglobin would not be found after storage. Sucrose is slightly more effective than the amino-acid, but oppositely, EDTA and Ficoll 70 do not allow prolonged storage of freeze-dried haemoglobin.
Actions of neurotransmitters and peptides on longitudinal and circular muscle of the rat portal vein
Authors: Mathison Ron
Published: April 2011

The reactivity of longitudinal and circular muscle of the rat portal vein to noradrenaline, acetylcholine, 5-hydroxytryptamine, substance P, angiotensin II and neurotensin was compared. Longitudinal muscle was prepared as longitudinal strips and circular muscle was studied as transversally cut rings. Longitudinal muscle was more sensitive than circular muscle to acetylcholine, 5-hydroxytryptamine and angiotensin II, whereas both muscle layers were equally sensitive to noradrenaline and substance P. Circular muscle was generally unresponsive to neurotensin. Differential sensitivity of longitudinal and circular muscle layers suggests that these two muscle layers do not necessarily operate in unison.
α2-Adrenoceptor agonist properties of exo- and endo-isomers of 2-amino-6,7,dihydroxybenzo-norbornene designed as rigid catecholamines
Authors: Hicks P E , Waldron C , Burn P , Crooks P A
Published: April 2011

A series of N-substituted exo- and endo-isomers of 2-amino-6,7-dihydroxybenzo-norbornene, designed as rigid catecholamines, have been studied in the pithed rat in-vivo, as vasoconstrictor agents, and as inhibitors of the twitch response in the transmurally stimulated guinea-pig ileum. The exo-isomers examined were vasoconstrictor agonists in the pithed rat and inhibited the twitch response of the ileum. The corresponding endo-isomers were inactive in both preparations. The exo-isomers were less potent than the α2-receptor agonist TL99, but were all directly acting vasoconstrictor agents, since they were still effective in reserpine-pretreated animals. Responses induced by members of the exo-series were selectively antanonized by the α2-receptor antagonist rauwolscine, but were not antagonized by the α1-receptor antagonist, prazosin, or the dopamine-receptor antagonist α-flupenthixol. The results demonstrate important conformational requirements for the interaction of catecholamines at presynaptic or postsynaptic α2-receptors, and suggest that a fully extended or anti-conformation of the noradrenaline molecule is involved in α2-receptor-agonist interaction.
Structure re-assignment of a metabolite of ampicillin and amoxycillin and epimerization of their penicilloic acids
Authors: Bird A E , Cutmore E A , Jennings K R , Marshall A C
Published: April 2011

Products formed in-vitro from ampicillin and amoxycillin penicilloates have been examined by high-performance liquid chromatography, ultraviolet and nuclear magnetic resonance spectroscopy and thiol group determination and were found to be the 5S epimers of the penicilloic acids. This is in contrast to a published claim that the corresponding penamaldic acids were formed by the treatment used.
Hypophysectomy does not prevent increased cerebral dopamine turnover following sulpiride administration
Authors: Reynolds L M , Dyer R G , Jenner P , Marsden C D
Published: April 2011

Hypophysectomy is claimed to prevent increased forebrain dopamine turnover produced by administration of sulpiride. We have measured the increase in dopamine metabolite concentrations caused by sulpiride following surgical removal of the pituitary. In saline-treated control animals and in hypophysectomized rats 1 week or 1 month following surgery, administration of sulpiride caused marked elevations of striatal, nucleus accumbens and tuberculum olfactorium, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations which were maximal 4–8 h following drug administration. The maximal increases in nucleus accumbens and tuberculum olfactorium were generally comparable in control and hypophysectomized animals, except for a greater increase in HVA levels in the nucleus accumbens 1 month following hypophysectomy. However, maximal increases in HVA and DOPAC in striatum were more pronounced in hypophysectomized rats 1 week or 1 month following surgery compared with control animals. At 30 min following sulpiride administration only inconsistent changes in dopamine turnover were observed in both control and hypophysectomized rats. Hypophysectomy does not prevent sulpiride from increasing forebrain dopamine turnover suggesting this is due to a direct interaction with cerebral dopamine receptors.
Adjustment of precompression force to reduce mixing-time dependence of tablet tensile strength
Authors: Vezin W R , Khan K A , Pang H M
Published: April 2011

The dependence of tablet tensile strength on lubricant mixing time, pre- and main compression pressure was measured with microcrystalline cellulose, dicalcium phosphate dihydrate and starch 1500 on a rotary tablet machine. Loss of tablet tensile strength arising from lubricant overmixing can be substantially reduced in the case of microcrystalline cellulose by adjustment of pre- and main compression. This facility may be used in addition to or instead of reducing mixing time, or displacing lubricant by adding extra formulation components.
Methadone radioimmunoassay: two simple methods
Authors: Robinson Katherine , Smith R N
Published: April 2011

Two simple and economical radioimmunoassays for methadone in blood or urine are described. Haemolysis, decomposition, common anticoagulants and sodium fluoride do not affect the results. One assay uses commercially-available [1−3H](-)-methadone hydrobromide as the label, while the other uses a radioiodinated conjugate of 4-dimethylamino-2,2-diphenylpentanoic acid and L-tyrosine methyl ester. A commercially-available antiserum is used in both assays. Normethadone and α-methadol cross-react to a small extent with the antiserum while methadone metabolites, dextropropoxyphene, dipipanone and phenadoxone have negligible cross-reactivities. The ‘cut-offs’ of the two assays as described are 30 and 33 ng ml−1 for blood, and 24 and 21 ng ml−1 for urine. The assay using the radioiodinated conjugate can be made more sensitive if required by increasing the specific activity of the label.
Acute effects on plasma lipids in the rat of a new long-acting nicotinic acid derivative: LG 13979
Authors: Subissi A , Criscuoli M , Biagi M , Murmann W
Published: April 2011

The effects on plasma lipids and nicotinic acid concentrations of a single dose of 2-(3-pyridinecarbonylamino)-2-deoxy-1,3,4,6 dihydrogen-D-glucose tetra-3-pyridinecarboxylate (LG 13979) compared with the effects of nicotinic acid and of its known derivatives niceritrol and sorbinicate, at the same doses, were studied in the fasted rat. Results show that LG 13979 has more prolonged activity on plasma free fatty acids and triglycerides, with longer lasting and more intense activity on plasma cholesterol than these three reference standards. Free fatty acid rebound occurs after administration of nicotinic acid and niceritrol, but not after LG 13979. This pharmacodynamic profile may be explained on the basis of the kinetics of nicotinic acid plasma concentrations, which are low, constant and lasting after LG 13979 administration.
Effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin output from rat stomach and renal papilla in-vitro and ex-vivo
Authors: Danon Abraham , Leibson Valentina , Assouline Georges
Published: April 2011

The effects of aspirin, indomethacin, flufenamic acid and paracetamol on prostaglandin (PG) biosynthesis were studied in whole cell preparations of rat renal papilla and stomach in-vitro and ex-vivo. In the ex-vivo experiments a low dose aspirin was a potent inhibitor of PGE output from the stomach but not the renal papilla, while in-vitro renal PGE output was inhibited by aspirin to a greater extent than gastric PGE. Indomethacin and flufenamic acid inhibited both renal papillary and gastric PGE outputs in-vitro and ex-vivo. Paracetamol enhanced PGE output from the stomach more than twice ex-vivo, and to a lesser extent in-vitro. It also augmented PGE output from the papilla ex-vivo but not in-vitro. In view of the possible contribution of cellular organization and pharmacokinetic processes to the ultimate effect, it is suggested that studies on the effects of anti-inflammatory and antipyretic agents on PG biosynthesis should not be restricted to fully in-vitro systems.
α-Adrenoceptor subtypes and Ca2+ mobilization the rabbit ear artery
Authors: Manzini Stefano , Maggi Carlo Alberto , Meli Alberto
Published: April 2011

The mobilization of cellular and extracellular Ca2+ pools by selective α1-adrenoceptor (phenylephrine) and α2-adrenoceptor (xylazine) agonists as well as noradrenaline was evaluated in rabbit ear artery. Noradrenaline and phenylephrine possess full instrinsic activity for both types of Ca2+ mobilization whereas xylazine up to 1 mM had only a limited contractile effect, being more effective in inducing extracellular Ca2+-dependent response. However, extracellular Ca2+ was mobilized by xylazine in a concentration 20 times higher than that required to stimulate pre-junctional α2-adrenoceptors. Noradrenaline (5 μM) and xylazine (1 mM) induced cellular and extracellular Ca2+-dependent contractions which were prazosin-sensitive and yohimbine-resistant. Xylazine-induced contractile activity, particularly that dependent upon the extracellular Ca2+ pool, was markedly reduced by selective adrenergic denervation with 6-hydroxydopamine, but the actions of noradrenaline were unaffected. These results suggest that: (1) rabbit ear artery contain post-junctional α1-adrenoceptor but not α2-adrenoceptors; (2) stimulation of these α1-adrenoceptors can account for the overall contractile activity of exogenously added noradrenaline and (3) stimulation of α1-adrenoceptors results in mobilization of cellular as well as extracellular Ca2+ pools.
Phase studies of ethoxylated surfactants-oil-water-undecylenic acid
Authors: Bulut F , Yalabik-Kas H S , Hincal A A
Published: April 2011

Two non-ionic surfactants (Simulsol OL 50 and Simulsol 98) separately or as 1:1 mixtures, together with corn oil-undecylenic acid and water formed various phases. Phase equilibrium studies were made. In all phase equilibrium diagrams investigated, both at 20 and 37°C, lamellar and hexagonal liquid crystalline and oily isotropic phases were found, besides the emulsion system. Emulsions were composed of mixed lamellar and hexagonal liquid crystalline phases which formed at low concentrations of surfactant and oil and correspondingly high water concentrations.
Photolytic degradation of frusemide
Authors: Moore Douglas E , Sithipitaks Varavudh
Published: April 2011

Irradiation with 365 nm u.v. light of frusemide (4-chloro-N-furfuryl-5-sulphamoyl-anthranilic acid) in methanol results primarily in photoreduction to N-furfuryl-5-sulphamoylanthranilic acid and photohydrolysis to 4-chloro-5-sulphamoylanthranilic acid (saluamine).
The production and properties of gel precipitated aluminium hydroxide spheres containing imipramine
Authors: Ramsey M P , Shaw G G , Newton J M , Lane E S , Sammon D C
Published: April 2011

The production of aluminium hydroxide spheres containing imipramine by gel precipitation of liquid feed solutions has been described. Washing and heating procedures applied to the precipitated spheres markedly affected the rate of drug release from the spheres into 0·1m hydrochloric acid. Increasing the imipramine content of the spheres also altered the drug release rate. The effects described have been explained with reference to model theories of the precipitation and ageing of aluminium hydroxide gels in the presence and absence of ‘foreign’ anions.
The assay of tropane derivatives in formulations by second derivative ultraviolet spectrophotometry
Authors: Hassan S M , Davidson A G
Published: April 2011

The development of a second order derivative spectrophotometric assay of atropine, hyoscine and benztropine in formulations is described. The assay involves the extraction into 1,2-dichloroethane of the tetraphenylborate salt of the alkaloids precipitated from pH 6 solution by an excess of sodium tetraphenylboron and measurement of the amplitude near 273 nm to its shorter wavelength satellite in the second derivative spectrum. The second derivative amplitude gives a more precise determination of the alkaloids than absorbance. A two-point bracketting standardization of the amplitude is required owing to a small but significant intercept in the calibration data. The procedures are sufficiently sensitive and precise for the batch and unit-dose assay of tablets of atropine sulphate (0·6 mg) hyoscine hydrobromide (0·3 mg) and benztropine mesylate (2 mg), and for the assay of atropine sulphate injection (0·4 mg ml−1) and tincture of belladonna.
Differential effects of vasodilators on the mobilization of calcium pools during contractions of rabbit ear artery induced by noradrenaline and high potassium
Authors: Maggi Carlo Alberto , Manzini Stefano , Meli Alberto
Published: April 2011

The effects of some vasodilators on the mobilization of different Ca2+ pools during contractions produced by noradrenaline and high K+ medium in rabbit ear artery has been investigated. Sodium nitrite was much more effective in antagonizing high K+-stimulated Ca2+ fluxes through the potential-dependent Ca2+ channels than noradrenaline-induced mobilization of intracellular Ca2+ stores or Ca2+ fluxes through receptor-operated channels. Papaverine was only slightly more active on contractions sustained by influx of extracellular Ca2+ (through potential-dependent channels and receptor-operated channels) than on those sustained by intracellular Ca2+. Verapamil and nifedipine were much more effective in antagonizing contractions sustained by Ca2+ entry through potential-dependent channels than through receptor-operated channels. Nifedipine was completely ineffective in antagonizing noradrenaline-induced mobilization of intracellular Ca2+ stores while verapamil had a limited inhibitory action in high concentrations. Phentolamine was equieffective in antagonizing both types of noradrenaline-induced contractions while having no effect on high K+-induced tonic contraction.
Effect of food, fluid and dosage form on the absorption of 52–522, a potential antianxiety agent, in the dog
Authors: Tse Francis L S , Jaffe James M , Marty Karen A , Schwarz Hans J
Published: April 2011

The absorption of 52–522 in the dog was studied by measuring blood concentrations of radioactivity after single oral doses of [14C] 52–522 in a capsule with and without water, also as a food-drug mixture, and a solution in polyethylene glycol 400. Absorption was rapid, and its rate moderate with no significant differences in peak times among treatments. The extent of absorption was lowest after the capsulated [14C] 52–522. The solution dose gave elevated blood concentrations, that were statistically significantly different when compared with the capsules. Hence, it appears that the absorption of [14C] 52–522 is governed by the degree of dispersion of drug in the dosage form.
Increased brain uptake of morphine in the presence of the antihistamine tripelennamine
Authors: Vadlamani N L , Pontani R B , Misra A L
Published: April 2011

Disposition of [6 3H (N)]morphine in plasma, brain and liver of rats was studied 15 min after intravenous injection of either a 2 mg kg−1 dose of morphine or a combination of the same dose of morphine with a 6 mg kg−1 dose of tripelennamine. The concentrations of morphine in brain and the brain to plasma morphine ratios in animals receiving the combination of drugs concurrently were significantly higher than those in the control morphine group. No significant differences were seen in the morphine or morphine metabolite concentrations in plasma and liver or liver to plasma morphine concentration ratios in the 2 groups. Data suggest that pharmacokinetic factors play a role in the potentiation of opiate effects by antihistamine on concurrent i.v. administration of the two drugs.
Influence of ricinoleic acid on the contractions elicited by PGE2 on the guinea-pig ileum
Authors: Capasso F , Mascolo N , Autore G , Duraccio M R
Published: April 2011

The effect of ricinoleic acid on prostaglandin E2 (PGE2)-evoked contractions was studied on guinea-pig isolated ileum. Addition of ricinoleic acid (10 μg ml−1) to the organ bath increased the amplitude of the PGE2-evoked responses. Ricinoleic acid (10 μg ml−1) also sensitized the guinea-pig isolated ileum to acetylcholine and histamine. The effect of the ricinoleic acid was greatly reduced by indomethacin either in-vivo (10 mg ml−1) or in-vitro (2 μg ml−1).
Evidence that drugs increasing 5-hydroxytryptamine transmission block jumping but not wet dog shakes in morphine-abstinent rats: a comparison with clonidine
Authors: Romandini S , Cervo L , Samanin R
Published: April 2011

(+)-Fenfluramine, a 5-hydroxytryptamine (5-HT) releaser and uptake blocker, m-chlorophenylpiperazine (CPP), a 5-HT receptor agonist, and clonidine, an agonist at adrenoceptors, were studied for their ability to modify jumping and wet dog shakes in morphine abstinent rats. (+)-Fenfluramine and CPP blocked jumping with no effect on wet dog shakes whereas the reverse was true for clonidine. The results further show that 5-HT mechanisms are preferentially involved in the expression of jumping in morphine-abstinent rats.
Comparative effects of inhibitors of the lipoxygenase enzyme system on leucocyte chemotaxis
Authors: Kitchen E A , Dawson W
Published: April 2011

The chemotactic response, towards zymosan activated serum (ZAS), of elicited peritoneal exudate leucocytes was assessed in-vitro after treatment with inhibitors of the lipoxygenase enzyme pathway. Leucocytes from both rat and guinea-pig were used. BW755C and benoxaprofen reduced the chemotaxis of mononuclear cells from both species at 10−4 m. Nordihydroguaiaretic acid (NDGA) at 7·5 times 10−6 m depressed the chemotaxis of rat mononuclear cells but failed to modify the response of guinea-pig mononuclear cells. NDGA, BW755C and benoxaprofen, at concentrations that inhibit the lipoxygenase enzyme pathway in-vitro, were ineffective in reducing the chemotactic response of rat PMN. All three agents potentiated guinea-pig PMN chemotaxis, to a greater or lesser extent, the most pronounced effect being with NDGA when increased PMN migration was accompanied by an increased detachment of cells from the lower surface of the filters. The effects of these agents on both cellular chemotaxis and adherence are not necessarily related to their inhibitory effects on the lipoxygenase enzyme pathway.
The rapid estimation of strychnine in tincture of nux vomica BP by high-performance liquid chromatography
Authors: Dennis R
Published: April 2011

Strychnine is separated from other alkaloids in nux vomica tincture in less than 6 min on a 12·5 cm Hypersil column using a mobile phase of methanol, 2 m ammonium hydroxide, m ammonium nitrate (27:2:1), uv detection at 254 nm. Quantitative estimation may be obtained by comparing peak area or height against an external standard (0·150% w/v strychnine base in 45% ethanol). The results obtained were comparable to those obtained by the BP method which takes 5 h.
Absorption of acetylsalicylic acid from enteric-coated tablets in relation to gastric emptying and in-vivo disintegration
Authors: Bogentoft Conny , Alpsten Magne , Ekenved Gunnar
Published: April 2011

The absorption of acetylsalicylic (ASA) acid from enteric coated tablets was studied in relation to gastric emptying and in-vivo disintegration. ASA tablets labelled with 51Cr were given to six healthy subjects under fasting and non-fasting conditions. The position and disintegration of the 51Cr-labelled tablets was followed by external radiation measurement and the amount of salicylic acid in blood and urine was analysed. The absorption of ASA from the studied enteric coated tablets was usually correlated with gastric emptying and in-vivo disintegration. However in some cases the absorption can be delayed between 10–20 h even if gastric emptying and disintegration of the tablet have occurred.