摘要:

Thein vitroandin vivoeffects of lead on the activity of pyrimidine‐5′‐nucleotidase (P5N, E. C. 3.1.3.5) and δ‐aminolevulinic acid dehydratase (ALA‐D, E.C. 4.2.1.24) were studied. Incubation of blood with lead at concentrations of up to 3 μmol/1 (about 60 μg/dl) did not appear to affect the activity of P5N, while the activity of ALA‐D decreased dose‐dependently with lead. Administration of lead caused a marked and rapid suppression of ALA‐D in rats. The suppression of lead on P5N appeared to be a rather slow process. The decrease of its activity only came into effect 20 days after administration with lead. These findings suggest that lead induced P5N inhibition is a slow process while the suppression of ALA‐D activity

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00695.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In order to clarify the physiological rolein vivoof H2O2‐detoxifying enzymes at low and high levels of O2tension we studied catalase (CAT), glutathione peroxidases (GP), andin vivoperoxidation (TBA‐RS) in the lung and heart ofRana perezifrogs chronically treated with hyperoxia, aminotriazole (AT) ‐a CAT inhihitor‐, or both. Hyperoxia did not change CAT, GP or TBA‐RS. Aminotriazole caused an almost complete depletion of CAT, a 30% decrease of GP and a 132% (lung) to 200% (heart) increase of TBA‐RS. Changes similar to these were found in the group treated with AT in hyperoxia. No mortality or changes in total or organ weight occurred in the experimental groups. Main conclusions are: (1) The maximal hyperoxia tolerance showed by frogs among vertebrates does not need antioxidant enzyme induction from lung or heart and is probably related to the presence of high constitutive levels of GP in relation to metabolic rate. (2) Even in normoxia the tissues present significant amounts of H2O2, and CAT is needed to avoid oxidative damage. GP does not compensate its absence. The implications of these results in relation to oxygen toxicity in man i

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00696.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effect of the putative antipsychotic compound amperozide on the electrical activity of single identified midbrain dopamine (DA) neurons was investigated in the chloral hydrate anesthetized male rat. While the activity of DA cells in the substantia nigra was unaffected, DA neurons of the ventral tegmental area (VTA), the origin of the mesolimbocortical DA system, were affected in either of two ways: 1) increased firing rate and burst firing, i.e. an excitation, or 2) regularization of the firing pattern. Reversible cold inactivation of the medial prefrontal cortex (PFC) induced a pacemaker‐like firing of VTA‐DA cells, an effect blocked by amperozide in the cells excited by the drug. Cells responding with a regularization were not protected against the effect of PFC inactivation. These different effects of amperozide, which may in part be mediated by 5‐HT2receptor blockade, suggest an antipsychotic activity of amperozide, particularly in schizophrenia with negative sym

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01603.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Five pregnant Rhesus monkeys were catheterized in the hepatic and femoral veins. They were simultaneously given 168 or 176 μg of3H‐metoprolol intravenously, and 9 mg of metoprolol per kg body weight orally. The same procedure was repeated a few months after delivery. Analyses of the unlabelled drug in blood were made by gas‐chromatography and of the3H‐labelled metoprolol, by liquid scintillation. The apparent volume of distribution as well as the terminal half‐lives of metoprolol were in the same range during pregnancy and in non‐pregnancy. The oral bioavailability of metoprolol was lower (6‐22%) during pregnancy than in non‐pregnancy (9‐49%). The apparent oral clearance and the intrinsic hepatic clearance were in a similar range although there was a greater variation in the intrinsic clearance values. The former clearance estimate was lower in the non‐pregnant state only for three of the five animals. The systemic clearance varied very little and was in the same range during pregnancy and in non‐pregnancy. The changes in apparent oral clearance and in oral bioavailability of metoprolol between the pregnant and non‐pregnant Rhesus monkey are similar to the changes observed in pregnant women, although the absolut

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00697.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractThe new putatively antipsychotic drug amperozide is characterized pharmacologically by a specific limbic mode of action. Thus amperozide is a potent antagonist of muricidal behaviour (ED50=0.16 mg/kg) as well as aggression between isolated male mice. Although amperozide displays anxiolytic properties in Vogel's conflict test as well as an antidepressive effect in the despair test, the drug does not interfere with motor coordination or cause sedation (ED50>50 mg/kg). These results could make amperozide very interesting as an antipsychotic drug in the clinic, with effect on both postive and negative symptoms.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01604.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb02072.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effects of amperozide on the synthesis and the turnover of monoamines in different brain regions of the rat were determined using bothex vivoandin vivobiochemical techniques (i.e.post‐mortem measurements of the tissue levels by HPLC‐EC, and direct measurements with thein vivovoltammetry technique). It was found that amperozide slightly increased the DOPA accumulation and the DOPAC content in limbic brain areas but not in the striatum. The DOPA accumulation was also slightly increased in the noradrenaline rich cortical region indicating increased synthesis of noradrenaline. Furthermore, amperozide increased the utilization of noradrenaline after tyrosine hydroxylase inhibition by α‐methyl‐p‐tyrosine. The synthesis of 5‐HT was not significantly altered by amperozide. In conclusion, the biochemical data obtained in this study suggest that amperozide produces preferential effects on the mesolimbic dopaminergic system. In addition, amperozide also interacts with the noradren

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01605.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Forced swimming stress caused a significant increase in the density of central type benzodiazepine binding sites in rat cerebral cortex and hippocampus. The number of peripheral type benzodiazepine binding sites was also enhanced on blood platelets. The affinity of neither central nor peripheral type benzodiazepine binding sites was changed considerably after swimming stress. Pretreatment of rats with β‐(phenyl)GABA (100 mg/kg), a GABABagonist, almost completely eliminated the described changes of the both types of benzodiazepine binding sites caused by swimming stress. In an elevated plus‐maze model of anxiety β‐(phenyl)GABA itself was inactive but like diazepam effectively counteracted the behavioural effects of DMCM, a β‐carboline derivative with anxiogenic properties. The possible involvement of benzodiazepine receptors in the mechanism of action of β‐(phenyl)GABA

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00699.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractAmperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [3H]‐dopamine in rat brainin vitro.Amperozide inhibited uptake of [3H]‐dopamine in striatal chopped tissuein vitrowith an IC50of 18 μM. It also increased basal release of [3H]‐dopamine from perfused rat striatal and limbic tissuein vitroat concentrations above 5 μM. Release of [3H]‐dopamine from perfused rat striatal and limbic tissue stimulated with 5 μM amphetamine, was inhibited by 1 μM amperozide to 46%. No significant difference was found for the effect of amperozide onin vitrorelease of [3H]‐dopamine from corpus striatum compared to tissue from limbic brain regions; neither on basal release nor on amphetamine‐stimulated rele

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01606.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractAmperozide, a new putatively antipsychotic drug was investigated for its effect on prolactin release in the rat. A significant decrease in the plasma concentration of prolactin was found at 30 minutes after treatment with amperozide. However, there was no effect of amperozide on prolactin release from isolated pituitary cells. These results suggest that there is no direct effect of amperozide on the pituitary lactotrophs and that the attenuation of prolactin secretion in vivo is mediated at a higher level.

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01607.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY