bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular withdrawal effects of clonidine and tiamenidine on abrupt cessation of oral treatment in conscious cats
Authors: Finch L , Hicks P E 
Published: April 2011

Abstract
In conscious renal hypertensive cats prepared with permanent indwelling arterial catheters oral administration of clonidine (0·05 mg × 3 daily) clonidine (0·0125 mg × 3 daily), or tiamenidine (0·25 mg × 3 daily) induced hypotension and bradycardia during 6 days of treatment, although these responses were not well sustained. A pronounced tachycardia was demonstrated in all cats, 16–20 h after cessation of treatment with the higher dose of clonidine, however, only two cats in this group showed increased blood pressures above pre-dose levels at this time; these ‘withdrawal’ effects were absent 44 h after the final dose. No evidence of tachycardia, or blood pressure overshoot was seen up to 44 h after cessation of the low clonidine treatment regime, providing evidence for a dose-withdrawal effect relationship. Significant tachycardia was demonstrated in all cats 15–19 h after cessation of treatment with tiamenidine with no evidence of blood pressure elevation; the tachycardia was absent 48 h after the final dose. In four of these same cats clonidine (0·1 mg × 2 daily), in a long-acting, sustained release formulation (LA clonidine), elicited prolonged falls in blood pressure and heart rate over a 10 day period. No evidence of withdrawal effects were obtained 14–48 h after cessation of this treatment.
Metabolite involvement in bromocriptine-induced circling behaviour in rodents
Authors: Reavill C , Jenner P , Marsden C D 
Published: April 2011

Abstract
Bromocriptine and apomorphine produced identical circling responses in rodents with medial forebrain bundle lesions. Rotation induced by bromocriptine, but not by apomorphine, was inhibited by prior treatment with reserpine or α-methyl-p-tyrosine suggesting a requirement for intact presynaptic events. Bromocriptine-induced circling also was inhibited by the catecholamine re-uptake blockers nomifensine and desmethylimipramine, supporting the role of presynaptic mechanisms. Bromocriptine-induced circling, but not apomorphine circling, was reduced by pre-treatment with SKF 525A, an inhibitor of monooxygenase enzymes, suggesting metabolite involvement in the turning response. This compound prolonged hexobarbitone sleeping times and zoxazolamine paralysis times in mice. These indices of drug metabolizing activity also were prolonged by pre-treatment with desmethylimipramine while nomifensine prolonged only hexobarbitone sleeping times and α-methyl -p tyrosine had no effect on either index. The data suggest that a metabolite of bromocriptine may be of importance in causing circling and that uptake of bromocriptine (or a metabolite) into presynaptic catecholamine terminals may be necessary.
Inhibition of intestinal water and electrolyte absorption by senna derivatives in rats
Authors: Leng-Peschlow Elke 
Published: April 2011

Abstract
Three intestinal segments were simultaneously perfused with Tyrode solution in the anaesthetized rat using a perfusion rate of 12 ml h−1. Dried purified senna extract containing 60% Ca-sennosides A + B (I) administered with the perfusion fluid had no or only minimal effects on intestinal absorption. Large doses (4 g litre−1) slightly reduced net Na, CI and H2O absorption predominantly in the colon and the ileum; the jejunum was unaffected. Dried purified senna extract containing 18% oxidized Ca-sennosides (II) reduced net Na, Cl and H2O absorption in all three intestinal segments, the effects increasing from the jejunum to the colon. Large doses (4 g litre−1) induced net Na and H2O secretion. II being administered with the colon perfusion fluid affected H2O and electrolyte absorption in the colon and to a lesser degree, in the ileum. Pure rhein (III, 0·28 g litre−1) had similar effects to II. Pure sennosides A + B (IV, 2 g litre−1) had no effect on intestinal absorption. These results confirm that changes in the absorptive behaviour of the gut mucosa are, at least partly, responsible for the laxative action of anthraquinone drugs and that this effect is mainly dependent on the presence of oxidized derivatives. There is evidence that the drug's effect is not locally restricted to the colon as is seen from the ileal response after intracolonic administration. Side-effects like griping which are sometimes observed after senna treatment seem to originate from motility changes rather than from changes in absorption.
Effects of glycine, β-alanine and diazepam upon morphine-tolerant-dependent mice
Authors: Contreras E , Tamayo L 
Published: April 2011

Abstract
The effects in mice of glycine, β-alanine and diazepam on the analgesic response to morphine, on the intensity of tolerance and on the physical dependence on the analgesic have been examined. The two amino acids increased the analgesic response to morphine in a doserelated manner. However, both compounds were ineffective in the analgesic test (hot plate) when administered without morphine. Diazepam was ineffective in the analgesic test and it did not alter morphine analgesia, except when administered in a high dose which decreased and analgesic response. Glycine, either in single or repeated doses, did not modify tolerance to morphine, whereas β-alanine induced a dose-related partial antagonism, which promptly reached a plateau. Diazepam induced a small decrease in the intensity of tolerance to the analgesic. The abstinence syndrome to morphine, induced by naloxone administration to primed mice, was reduced by single doses of glycine or β-alanine. Diazepam behaved as a weak inhibitor of the abstinence syndrome when administered at a high dose. The potentiation of morphine analgesia and the antagonism of the abstinence syndrome induced by the amino acids may be related to their hyperpolarizing action in the c.n. system. The effects of β-alanine on morphine tolerance cannot be explained by the same mechanism.
Effects of 3,4-dihydroxyphenylpyruvic acid and L-glutamic acid on some pharmacokinetic parameters of L-dopa in the rat
Authors: Lindén Inge-Britt 
Published: April 2011

Abstract
In the rat, various oral doses of 3,4-dihydroxyphenylpyruvic acid (DHPPA) administered simultaneously with L-dopa were shown to elevate the serum L-dopa and cerebral dopamine concentrations dose-dependently. With increasing DHPPA: L-dopa ratio the L-dopasparing effect became greater. Although oral and intravenous doses of DHPPA showed that it was readily converted to L-dopa in the serum, only small amounts of dopamine (DA) were detected in the brain. The high 3-O-methyldopa concentrations, measured in the serum after DHPPA administration, might be responsible for the failure of the L-dopa formed to pass the blood-brain barrier. Concomitant administration of L-dopa and glutamic acid gave significantly higher L-dopa values in the serum and DA and homovanillic acid values in the brain than did the same dose of L-dopa alone. This indicates that the transamination of L-dopa can also be effected by coadministration of L-dopa and an amino group donor in vivo.
The effect of proteolytic enzymes on the disposition of tetracycline
Authors: Edwards G , Calvert R T 
Published: April 2011

Abstract
The acute administration of a mixture of trypsin and chymotrypsin did not significantly affect the rate or extent of disappearance of tetracycline from the rat gut in situ, nor did chronic administration of enteric coated tablets containing trypsin and chymotrypsin to rats significantly influence the rate or extent of absorption of tetracycline compared with rats receiving enteric coated placebo tablets. Similarly, chronic enzyme administration did not effect either the systemic clearance, half life or apparent volume of distribution of intravenously administered tetracycline compared with rats receiving placebo tablets.
Are the pA2 values of selective β-adrenoceptor antagonists valid when obtained on guinea-pig tracheal preparations contracted with carbachol?
Authors: O'Donnell Stella R , Wanstall Janet C 
Published: April 2011

Abstract
On carbachol-contracted tracheal preparations from guinea-pigs, the slope of the Schild plot for propranolol (isoprenaline as agonist) was 1·0. The slope of the plots for atenolol β1selective) and butoxamine (β2-selective) were less than 1·0, whether isoprenaline or fenoterol was agonist. This was in contrast to previous reports on intrinsic tone tracheal preparations. It was established that the low slopes for atenolol and butoxamine on carbachol-contracted preparations were not related to aspects of the experimental procedures. Low slopes on carbachol-contracted preparations tended to occur when the antagonist used was selective and, although the reason for this is not clear, it may be related to the presence of both ft- and β2-adrenoceptors in this tissue. Therefore, it is suggested that pA2 values obtained for selective β-adrenoceptor antagonists on guinea-pig tracheal preparations contracted with carbachol may not be strictly valid, and that antagonists should be studied on intrinsic tone tracheal preparations when pA2 values are to be compared with pA2 values from other tissues to quantify the selectivity of the antagonist.
Central cardiovascular and biochemical effects of baclofen in the conscious rat
Authors: Persson Bengt , Henning Matts 
Published: April 2011

Abstract
Baclofen (β-p-chlorophenyl-GABA, 1–25-10 mg kg-1 i.p.) elicited dose-dependent increases in blood pressure and heart rate in conscious rats. Similar responses were observed after intracisternal or intracerebroventricular injections of baclofen 0·125-1 μg kg−1. Baclofen i.p. was largely ineffective after spinal transection at C7, Pretreatment with phenoxybenzamine, bethanidine or hexamethonium antagonized the cardiovascular effects of i.p. baclofen. These actions were significantly attenuated after catecholamine depletion and synthesis inhibition by means of α-methyl-m-tyrosine and α-methyl-p-tyrosine. The responses to baclofen were not affected by bilateral adrenal demedullation but abolished by pentobarbitone anaesthesia. Hence, the cardiovascular effects of baclofen are probably evoked from central nervous structures and mediated via the sympathetic nervous system. In doses corresponding to those used in the circulatory studies i.p. baclofen increased endogenous concentrations of brain DA and decreased DA utilization but only slightly affected brain NA concentrations and utilization.
Zero order drug delivery from double-layered porous films: release rate profiles from ethyl cellulose, hydroxypropyl cellulose and polyethylene glycol mixtures
Authors: Donbrow M , Samuelov Y 
Published: April 2011

Abstract
Laminated double-layered films comprising a drug-containing and drug-free layer were prepared using tripelennamine, barbitone, salicylic acid and caffeine dispersed in hydroxypropylcellulose (HPC) attached to ethyl cellulose (EC) films containing various proportions of polyethylene glycol (PEG) or HPC to enhance permeability. Drug release in vitro followed zero-order kinetics, rate constants being dependent on the thickness of the drug-free membrane, which was rate-controlling. Thickness-corrected zero order constants were independent of drug-loading, which did, however, control the duration of release. Permeability coefficient measurements on the same rate-controlling films used as single barrier membranes enabled the effective drug concentration (Co) at the interface between the laminated membranes to be estimated; Co was independent of drug loading and was of the order expected from the aqueous solubilities of the drugs. Release rates were enhanced by addition of hydrophilic polymer to the rate-controlling membranes, either linearly with fraction of additive for PEG to 0·6 or HPC to 0·4, or logarithmically for HPC from 0·4 to 0·8. Enhancement coefficients, which were different for each system, reflected the different mechanisms of hydrophilic polymer action. PEG was leached out rapidly, pores being formed in the matrix. In contrast, HPC was largely retained, so that the enhancement was less. The logarithmic enhancement stemmed from formation of swollen hydrated channels, which, unlike the low HPC fractions or the PEG systems, allowed entry of buffer ions, so that only in these channel systems were the release rates altered by change of the external pH.
Effects of 5-hydroxytryptamine, fluoxetine and chlorimipramine on reflex bradycardia in rats
Authors: Lin M T , Tsay B L , Fan Y C 
Published: April 2011

Abstract
In the urethane-anaesthetized rat, increasing 5-hydroxytryptaminergic receptor activity or functional 5-HT in brain with either the specific inhibitors of 5-HT reuptake (e.g. fluoxetine and chlorimipramine) or the 5-HT itself greatly reduced the reflex bradycardia induced by the systemically administered adrenaline. The data indicate that activation of central 5-HT-ergic receptors tends to inhibit reflex bradycardia.
Aspirin binding and the effect of albumin on spontaneous and enzyme-catalysed hydrolysis
Authors: Aarons Leon , Clifton Patricia , Fleming George , Rowland Malcolm 
Published: April 2011

Abstract
A method of measuring the binding of aspirin to albumin without the interference of hydrolysis was developed. At concentrations of 10 mg litre−1, aspirin is about 85% bound to bovine serum albumin (4 g%), whereas its hydrolysis product, salicylic acid, is 95% bound. Salicylic acid was shown to displace aspirin from albumin binding sites. Both salicylic acid and aspirin bind more strongly to bovine serum albumin than to human serum albumin at protein concentrations of 4 g%. Protein binding protected aspirin against spontaneous hydrolysis although protein-bound aspirin still hydrolysed at a finite rate. In contrast, albumin enhanced the enzyme-catalysed hydrolysis of aspirin. By using a simple model, the rate constants for the individual processes contributing to the overall hydrolysis rate constant in the presence of albumin and esterase are calculated.
In vitro metabolic effects of gliclazide and glibenclamide in the rat
Authors: Musbah M O , Furman B L 
Published: April 2011

Abstract
The actions of gliclazide and glibenclamide on glucose uptake and glycogen deposition by rat hemidiaphragm and glucose utilization by rat epididymal adipose tissue have been examined in vitro. Neither drug exerted an insulin-like action on muscle or adipose tissue with respect to glucose uptake, glycogen deposition or glucose utilization. Neither gliclazide nor glibenclamide augmented the stimulating action of insulin on glucose uptake or glycogen deposition in the rat hemidiaphragm. In a high concentration (1 μgg ml−1), but not in lower concentrations, glibenclamide enhanced the action of insulin in stimulating glucose utilization by rat epididymal adipose tissue. Gliclazide was without any significant effect. Twenty eight day oral treatment with gliclazide did not increase basal or insulin-stimulated glucose uptake or glycogen deposition in rat hemidiaphragm muscle or glucose utilization by epididymal adipose tissue. It is concluded that in normal rats sulphonylureas do not exert important insulin-like actions or insulin potentiating effects.
Effects of two glucose absorption inhibitors: phenformin and 43–522 on hepatic gluconeogenesis
Authors: Ho R S , Kelly L A 
Published: April 2011

Abstract
The glucose absorption inhibitors, Phenformin and 3-phenylpropylaminoguanide HCl (SaH 43–522) have different effects on hepatic gluconeogenesis. Unlike phenformin, 43–522 in vivo does not inhibit hepatic gluconeogenesis; inhibition occurred only when 43–522 was added directly to a liver perfusion system. This suggests that when 43–522 is administered in vivo it is metabolized to an agent that does not inhibit hepatic gluconeogenesis whereas phenformin is not metabolized, and does inhibit gluconeogenesis. This is an advantage of 43–522 since it thereby specifically inhibits intestinal glucose absorption without a potential hypoglycaemic effect due to the suppression of gluconeogenesis.
The effect of viloxazine on drug-induced inhibition of food intake in the rat
Authors: Pleece S A , Kirby Marilyn J , Redfern P H 
Published: April 2011

Abstract
In male Wistar rats trained to eat their normal daily dietary requirement in a restricted 2 h period, dose-dependent decreases in food consumption were produced by fenfluramine, tiflorex, mazindol and amphetamine. The antidepressant drug viloxazine (Vivalan) alone did not alter food intake significantly, nor did the drug prevent the inhibitory effects of either mazindol or amphetamine. However, complete prevention of the inhibitory effect of fenfluramine was achieved with 7·5 mg kg−1 viloxazine, while 40 mg kg−1 viloxazine similarly prevented the anorectic action of tiflorex. An interaction involving 5-hydroxytryptaminergic mechanisms is suggested, and since viloxazine given after fenfluramine or tiflorex produced no reversal of the inhibition of food intake, it is suggested that viloxazine prevents access of the anorectic agents to their site of action. The clinical significance of these interactions is discussed.
The differential effects of morphine, oxotremorine and antipsychotic drugs on DOPAC concentrations in rat brain
Authors: Stanley Michael , Wilk Sherwin 
Published: April 2011

Abstract
The effects of morphine and oxotremorine on concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat striatum and tuberculum olfactorium (TO) have been compared with the effects of the antipsychotic drugs haloperidol, chlorpromazine and clozapine. All the drugs elevated DOPAC concentrations in both brain regions. While the dose-response curves for the antipsychotic drugs were parallel, had steep slopes and similar maxima, the curves for morphine and oxotremorine were irregularly shaped but the curve for morphine in the TO had some similarity to that of the antipsychotic drugs. From these findings, it is concluded that the dose-dependent increase in striatal DOPAC effected by antipsychotic drugs can be used to differentiate them from other drugs known to elevate dopamine metabolites.
Molecular connectivity and gas chromatographic retention parameters
Authors: Millership J S , Woolfson A D 
Published: April 2011

Abstract
The relation between gas chromatographic retention parameters and molecular connectivity has been investigated for several series of compounds including hydrocarbons, compounds containing oxygen functional groups (esters, aldehydes, ketones, alcohols and ethers) and drug molecules. With the oxygenated compounds good correlation was observed with the first order valence connectivity index, whilst for the other groups multiparameter equations were required for satisfactory correlation. The effect of column to column variation within a series was also investigated.
Effects of olfactory bulbectomy and peripherallyinduced anosmia on thermoregulation in the rat: susceptibility to antidepressant type drugs
Authors: Forster Christine , Parkes Janet , Cox B 
Published: April 2011

Abstract
Olfactory bulb ablation in the rat produces an acquisition deficit in a step-down passive avoidance test, hyper-reactivity to environmental stimuli, elevated plasma-11-hydroxycorticosterone, and a deficit in the thermoregulatory response to low ambient temperatures, which is not evident at normal ambient temperatures. Like the other features of the bulbectomy syndrome, this thermoregulatory deficit is not related to anosmia per se, since rats made peripherally anosmic with intranasal ZnSO4 (5%) do not show a thermoregulatory deficit at low ambient temperatures. The abnormal response to cold could be prevented by chronic daily administration of amitriptyline (10mg kg−1), mianserin (10mg kg−1), and the 5-HT uptake inhibitor, Org 6582 (10 mg kg−1) for 7 days. The possibility that the thermoregulatory deficit has the same biochemical basis as the behavioural changes is discussed and a 5-HT involvement in the syndrome is considered.
Drug distribution as a function of binding competition. Experiments with the distribution dialysis technique
Authors: Bickel Marcel H , Gerny Rolf 
Published: April 2011

Abstract
In the distribution dialysis technique each of the two dialysis chambers contains a binding system, and a drug is allowed to distribute between them. This technique was tested by using various intracellular and extracellular binder preparations over wide concentration ranges, and model drugs selected for their known binding properties. The drugs were then tested at therapeutic concentrations in standardized systems of liver homogenate (0·5 g ml−1) and whole blood (0·02 ml ml 1) The resulting intracellular/extracellular concentration ratios were characteristic for the binding properties of the various drugs. Thus, for imipramine, a drug with strong tissue and weaker plasma binding properties, the concentration ratios were 25 for the system homogenate/buffer, 0·8 for buffer/blood, and 15 for the competitive system homogenate/blood. In experiments with homogenates from various tissues (liver, lung, kidney, intestine, brain) and blood in the standard system, the following approximate ratios were obtained: 1 for antipyrine, 2 for phenylbutazone, 14 for imipramine (but only 8 with muscle, skin and adipose tissue). These results reflect both the individual binding to intracellular and extracellular components and the tissue/blood concentration ratios in vivo. It is suggested that distribution dialysis is an in vitro method for characterizing the distribution of drugs. It is also concluded that drug distribution is largely determined by a binding competition between tissue and blood sites.
Participation of adrenal medulla in 6-aminonicotinamide-induced hyperglycaemia in the rat
Authors: Kaul C L , Talwalker P K , Grewal R S 
Published: April 2011

Abstract
In fasted rats 6-aminonicotinamide (6-AN) produced delayed hyperglycaemia, the peak effect being seen by 7 h. Fasting plasma insulin concentrations were not significantly altered but liver glycogen concentrations were decreased following treatment with 6-AN. Adrenalectomy, demedullation and pretreatment with reserpine, phentolamine, nicotinamide and nicotinic acid completely blocked the hyperglycaemic response whereas guanethidine and propranolol or oxprenolol were ineffective. Catecholamine concentrations in the adrenal venous plasma were markedly increased by treatment with 6-AN, the peak effect being seen by 5 h. It is concluded that adrenal medullary release, which is slow in onset, is mainly responsible for the development of sustained hyperglycaemia in the rat.
Regional differences in the responses to prostanoids of circular muscle from guinea-pig isolated intestine
Authors: Sanger Gareth J , Bennett Alan 
Published: April 2011

Abstract
The effects of prostaglandins (PGs) D2, E2, F2α, an epoxymethano analogue of PGH2 (U-46619), prostacyclin (PGI2), 6-keto-PGFlα and thromboxane (Tx) B2 were tested on spirally-cut strips of guinea-pig isolated ileum or colon. In the ileum no prostanoid exerted a marked effect on the resting tissue, but PGD2, PGE2 or PGI2 1 μg ml−1 inhibited submaximal contraction to KC1. U-46619 1 μg ml−1 either inhibited or increased contractions to KC1, but PGF2α, 6-keto-PGF1α or TxB2 1 μg ml−1 had no significant effect. PGE2 relaxed colonic strips whereas the other prostanoids caused contraction, except for TxB2 which had no effect. The PG antagonist SC-19220 blocked colonic contractions to the prostanoids, and a residual inhibitory effect of PGD2, U-46619 or PGI2 was demonstrated by the reduction of submaximal contractions to acetylcholine. Our results suggest that prostanoid receptors mediating inhibitory responses of circular muscle predominate in the ileum, whereas in the colon both excitatory and inhibitory prostanoid receptors occur.