摘要:

Abstract:The aim of the study was to examine the role of serotonergic (5‐HT) and noradrenergic mechanisms in the regulation of wakefulness and sleep. For this purpose, adult cats with implanted electrodes for EEG, EOG and EMG were exposed to the 5‐HT uptake blocker citalopram (0.1, 0.5 and 5.0 mg/kg intraperitoneally) and the noradrenaline uptake blocker prindamine (5 mg/kg intraperitoneally) at the start of continuous 16‐hour sleep‐wake recordings. Citalopram increased deep slow wave sleep and decreased REMS. Also prindamine decreased REMS but initially increased the proportion of time spent in the state of active wakefulness. Furthermore, to examine the interactions between 5‐HT‐nergic and noradrenergic mechanisms in the regulation of sleep, the administration of citalopram was preceded by intraperitoneal injections of phentolamine (10 mg/kg), an α‐antagonist, and propranolol (5 mg/kg), a β‐antagonist. Phentolamine was totally ineffective against citalopram whereas propranolol partially counteracted the effects of citalopram on sleep. Prindamine was combined with the β‐antagonists yohimbine (1 mg/kg), phentolamine (10 mg/kg) and prazosin (1 mg/kg) or with the β‐antagonist propranolol (5 mg/kg). Yohimbine was without any effect on REMS, phentolamine partly antagonized prindamine‐induced decrease in the percentage of REMS, and prazosin only prolonged REMS latency and reduced deep SWS as well. Propranolol partially antagonized the prindamine‐induced initial increase in active wakefulness time. These results indicate that while both citalopram and prindamine suppress REMS, the concurrent increase in the amount of DSWS in the case of citalopram administration may be related to 5‐HT‐ergic mechanisms whereas the increase in active wakefulness occurring concurrently with inhibition of REMS in the case of prindamine administration may be related to noradrenergic mechanisms. The possible role of α‐ and β‐adrenoceptors in the mechanisms of the desc

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01725.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The formalin and writhing tests in mice were employed to investigate a possible delay in the onset of antinociceptive action of acetylsalicylic acid (ASA). Drugs were given 30 min. before the noxious stimulation by either formalin or acetic acid. In the formalin test, the difference between the drug treated groups and the control group reached statistical significance within 30 sec. of noxious stimulation. ASA (400 mg/kg intraperitoneally) and morphine (5 mg/kg intraperitoneally) treated groups were not significantly different in any of the ten periods (30 sec. each) that were analysed during the first 5 min. In the writhing test, the number of writhings in response to intraperitoneal injection of acetic acid was counted during the first 20 min. The difference between the drug treated groups and the control group reached statistical significance after 3 min. both for ASA (400 mg/kg subcutaneously) and morphine (2 mg/kg subcutaneously) and no significant differences between the drug treated groups were found in any of the one min. periods that were analysed. Thus no delay of onset in the action of ASA compared to morphine could be demonstrated, and ASA seems to be antinociceptive also in acute non‐inflammatory pain. Actions apart from inhibition of the synthesis of prostaglandins are suggested for this effect of AS

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01726.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Liver injury was induced by one subcutaneous administration of thioacetamide (200 mg/kg b.wt.) and studied 24 and 48 hrs later. Levels of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) increased after 24 and 48 hrs. The lysosomal enzymes β‐hexosaminidase (β‐NAG) and β‐glucuronidase (β‐GLU) increased significantly after 24 hrs, while the level of β‐GLU returned to normal after 48 hrs, but the activity of β‐NAG remained significantly high even after 48 hrs. Histopathological examination showed necrotic hepatocytes around the central vein with infiltration of macrophages, neutrophils and eosinophils. The plasma zinc level decreased after 24 hrs and returned to normal after 48 hrs. Liver zinc content increased simultaneously at 24 hrs, returning to normal after 48 hrs. No alterations of plasma copper were observed after 24 and 48 hrs. Copper content of the liver increased significantly after 24 and 48 hrs. The present study thus shows that one dose of thioacetamide results in profound liver injury and supplementation of zinc prior to and simultaneously with thioacetamide normalized plasma zinc, increased liver zinc content and reduced the increase of β‐NAG, but did not influence the

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01727.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The acute effect of instillation of the spermicide 2% nonylphenoxypolyethoxyethanol (nonoxynol‐9) on the bioelectric activity of the vaginal epithelium was assessed using as an index the time taken in seconds to reduce the transvaginal potential difference (p.d.), measured in anaesthetised rats, to half its initial value (t½). The surfactant caused rapid falls in the p.d. at dioestrus (t½ = 35 ± 25 sec., n= 16, mean ± S.D.) and metoestrus (t½ = 32 ± 27 sec., n= 11) with a slower fall at oestrus (t½ = 130 ± 104 sec., n= 14). At pro‐oestrus however, nonoxynol‐9 had no effect (n= 18). The dye Nigrosin (0.5%), when instilled alone, did not stain untreated vaginas of anaesthetized rats at any stage of the oestrous cycle, but in the presence of 2% nonoxynol‐9 heavily stained those in metoestrus and dioestrus. Vaginas in pro‐oestrus were unstained while those in oestrus were stained lightly. While nonoxynol‐9 has a dramatic effect on the bioelectric activity of the vaginal epithelium, both the electrical and dye data show that the pro‐oestrus vaginal epithelium presents a significant diffusion barrier to the passage of nonoxynol‐9 and nigrosin. Thus, in assessing the actions of vaginally instilled nonoxynol‐9 in rats the variation in the permeability of the vaginal epithelium during the oestrous cycle m

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01728.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Intravenous treatment with disopyramide is usually performed by administration of a bolus injection of 150 mg given over 5 min. followed by a continuous infusion of 18‐24 mg hour‐1. A decrease in cardiac output is associated with this rapid bolus injection. Seven patients with ischaemic heart disease entered an open randomised cross‐over trial to elucidate if an extension of the bolus injection time to 20 min. resulted in a smaller decrease in cardiac output. Cardiac index decreased significantly (P<0.001) in both situations, with maximum decrease observed at time 5 and 20 min., respectively (equivalent to the ending of the administration of 150 mg disopyramide). The decrease in Cardiac index (mean ± S.E.M.) was identical in the two situations (2.56 ± 0.23 to 1.78 ± 0.21 1/min. × m2(30%) and 2.66 ± 0.17 to 1.94 ± 0.19 1/min. × m2(27%)), respectively. Blood pressure was unchanged, while heart‐rate (P<0.025) and preejection period index (P<0.005) increased significantly and to the same extent in the two situations. Significant correlations between the log free and log total serum concentration of disopyramide and the relative change in preejection period index of r = 0.840 (P<0.01) and 0.919 (P<0.01), respectively, were observed giving disopyramide over 5 min. A significant anticlockwise hysteresis was observed extending the time of administration to 20 min. As no haemodynamic advantages are achieved by the slower way of administration we would still recommend the bolus injection to be gi

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01729.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The microsomal Na+‐K+‐ATPase of rat brain was inhibited by mercury chloride and methyl mercury. The IC50was 6.5 × 10‐7M for mercury chloride and 3.5 × 10‐6M for methyl mercury. The inhibition was of a non‐competetive type with respect to ATP. The non‐ionic detergent Lubrol$rGpotentiated the inhibitory effect of both mercurials. It is concluded that Lubrol$rGremoves the bulk lipids present outside the catalytic center of the enzyme. Consequently, the enzyme will become more sensitive to the inhibition by bo

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01730.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Purified14C‐labelled peptide toxin from the cyanobacteriumMicrocystis aeruginosawas administered intraperitoneally to mice and the distribution of label determined between the major organs. Seventy per cent of the label was localized in the liver after 1 min.; this value increasing to almost 90 per cent after 3 hours. Label associated with the lungs and other individual organs varied between 10 and 1 per cent of the14C recovered throughout. Three microsomal enzyme inducers, β‐naphthoflavone, 3‐methylcholanthrene and phenobarbital, afforded protection against liver damage and extended survival if given to mice before the administration of an LD50 dose of toxin. Toxin‐dependent changes in liver cytochrome levels were also reduced by the enzyme

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01731.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The myocardial pharmacodynamic effects of the two dihydropyridine calcium‐antagonists nicardipine and nitrendipine were comparatively studied in the isolated, spontaneously beating and retrogradely perfused rabbit heart at stepwise increased drug concentrations within the range 0.5‐260 ng·ml‐1(1.1‐721 nM). Both drugs produced a progressive and very pronounced inhibition of myocardial contractility as measured by both contraction amplitude and contraction velocity. The corresponding Emax‐values were about 100% and IC50‐values about 10 and 65 nM, respectively. Myocardial oxygen consumption did not decrease at the lower concentrations of neither nicardipine nor nitrendipine but were at the higher levels inhibited significantly with Emax‐values of about 68 and 78% and IC50‐values about 21 and 136 nM, respectively. Coronary flow‐rate increased at the lower concentrations of the drugs to about 125 and 118% and then decreased to 80 and 77%, respectively. Both drugs, but especially nitrendipine, showed a marked negative chronotropic effect (Emax33 and 56% and IC50 6 and 81 nM, respectively). The frequency‐corrected QT‐intervals were progressively decreased by the drugs. Myocardial accumulation and disposition pharmacokinetics of nicardipine, nitrendipine and nimodipine were also studied. The terminal half‐lives for the drugs were about 56, 16 and 29 min., respectively. Apparent relative volumes of drug distribution in the myocardium which equals the average concentration ratio for the drugs between this tissue and the perfusion liquid at kinetic steady‐states were about 290, 61 and 177 ml·g‐1, respectively. Although nicardipine and nitrendipine accumulated slowly at different rates in the rabbit heart both drugs produced a faster progressing and very marked negative inotropic effect and a less than proportional reduction in oxygen consumption accompanied by an only initial i

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01732.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:The gastrointestinal (GI) absorption in mice of the anticholinergic quaternary ammonium compound emepronium, assessed by the urinary excretion of radioactivity and unchanged drug, increased from 1% to 7% and from 0.5% to 5%, respectively, in the dose range 0.1 to 40 mg/kg, whereafter a plateau was reached. Changes in the metabolism were evident at doses exceeding 80 mg/kg when 80% of the radioactivity was excreted as unchanged emepronium, as compared to 50% at lower doses. No dose‐dependent urinary excretion of radioactivity was detected following intravenous injection. The increase in the fraction of the dose excreted in the urine after oral administration therefore cannot be easily explained by a dose‐dependent metabolism or renal excretion. However, a relationship was seen between the reduced gastrointestinal motility, produced by increasing doses of the drug, and the increased bioavailability. Atropine sulphate given subcutaneously (1–50 mg/kg) more than doubled the urinary recovery of a small pharmacologically inactive oral dose of emepronium (5 mg/kg) and thus confirmed the transit rate‐dependent absorption of emepronium. The superimposed effect of the pharmacological action on the GI transit rate, derived from the inherent property of an anticholinergic drug, may be of special significance for a drug with a low degree of absorption and a high variability, such as has been observed in clinical trials with the quaternary drug emepronium (Cet

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01733.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

Abstract:Thein vitroexposure of rat bronchial smooth muscle to the acetylcholinesterase inhibitor soman (0‐[1,1,2‐trimethylpropyl]‐methylphosphonofluoridate) reduced the potassium (51 mM) evoked release of3H‐acetylcholine (3H‐ACh). Exposure to 1.0 and 100 μM soman for 15 min inhibited the acetylcholinesterase (AChE) activity completely and reduced the potassium evoked release by 23.1% and 34.4% respectively. In the presence of scopolamine (0.3 μM), however, there was a large enchement (87.0%) of potassium evoked release during soman inhibited (100%) AChE‐activity. Furthermore, soman (1.0 μM) did not reduce the spontaneous release of3H‐ACh. The results indicate that the presynaptic effect of soman is due to the enhanced concentration of ACh following AChE‐activity inhibition in the synaptic region. This induces a stimulation of presynaptic muscarinic receptors and thereby modulation of the ACh release only dur

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1987.tb01734.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY