摘要:

Peripheral-type benzodiazepine (BZ) receptors (PBRs) have been identified in various peripheral tissues as well as in glial cells in the brain. PBRs are located mainly on the outer mitochondrial membrane and bind with high affinity the BZ Ro 5–4864 (4'-cholorodiazepam) and the non-BZ PK 11195 (an isoquinoline carboxamide derivative), but bind with very low affinity the BZ clonazepam. PBRs have been cloned from various species. PBRs are multimeric receptors composed of the 18-kDa binding site for isoquinolines, the 32-kDa voltage-dependent anion channel, and the 30-kDa adenine nucleotide carrier (which binds BZs). The expression of PBRs is especially high in steroidogenic organs. Steroid administration affects PBR density, whereas depletion of hormones by hypophysectomy in female rats, or castration (surgical or chemical) in male rats, decreases PBR density in endocrine organs, which can be elevated to normal values after administration of the appropriate hormone. PBRs are probably involved in several functions, including cell proliferation, respiration, and Steroidogenesis. It has been suggested that PBRs are involved in the translocation of cholesterol from the outer to the inner membrane of the mitochondria and have an effect on the biosynthesis of steroids.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Summary:Melatonin is a neurohormone produced during the night by the pineal gland. Its secretion is regulated by circadian and seasonal variations in daylength, transmitted via visual projections to the suprachiasmatic nucleus which functions as a circadian clock in mammals. Melatonin has been proposed to act as an internal synchronizer of circadian rhythms generated at different levels of the organism. The chronobiotic effects of melatonin in humans have been mainly studied in circadian rhythm sleep disorders related to jet lag, shift work, blindness or aging. Alterations of the melatonin profiles have also been reported in other biological rhythm disorders.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In the present study, effects of citalopram (CIT) on brain 5-hydroxytryptamine (5-HT) release in experimental chronic hepatic encephalopathy (HE) were investigated. Neocortical administration of CIT (1.0 μM) increased the brain 5-HT output to a similar extent in portacaval shunted (PCS) rats and sham-operated controls, indicating that a previous described mismatch between increased 5-HT turnover and unchanged release in PCS rats is not explained by an accelerated brain 5-HT reuptake. Subsequent systemic administration of CIT (5 mg/kg subcutaneously) resulted in a more pronounced attenuation of the brain 5-HT release in PCS rats than in sham-operated controls, possibly indicating a higher susceptibility to indirect mid-brain 5-HT1Aautoreceptor activation in experimental portal-systemic encephalopathy (PSE). A KCl (60 mM) challenge in the presence of locally administered CIT (1 μM) induced a more marked neocortical 5-HT response in PCS rats than in sham-operated controls, confirming previous results of a higher than normal amount of 5-HT available for depolarization-induced release in PCS rats. Although the pharmacodynamic parameters in this study was investigated for CIT, the likelihood of a parallel pharmacokinetic alteration existing for this drug in the PCS condition also was indicated. It is thus suggested that otherwise generally safe central nervous system 5-HT-active drugs may represent a potential hazard in patients with liver failure with or without PSE.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We report on motor complications of chronic levodopa therapy among 811 levodoparesponsive patients with idiopathic Parkinson's disease (PD), stratified by duration after diagnosis. Predictable “offs” were noted in 20.2% of patients in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and early morning dystonia were less common. Longer duration was associated with greater percentages of patients with off periods or dyskinesias (up to 70% after 15 years), although patients with 6–15 years' duration saw relatively little increase in frequency of those complications, and a minority of patients (∼30%) with duration into the second decade did not experience off periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era. We note that with advancing PD duration, levodopa complications are more common, but in many cases there appear to be relatively stable periods in terms of levodopa dosage and disease severity, and a minority of patients will be relatively free of motor complications into the second decade of their disease.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Summary:Tolcapone (Ro 40–7592) is a novel inhibitor of catechol-O-methyltransferase that is being developed for clinical use in the treatment of Parkinson's disease as add-on therapy to a combination of levodopa and a peripheral amino acid decarboxylase inhibitor (benserazide or carbidopa). The current single-blind, randomized study was designed to evaluate the effect of tolcapone compared with placebo on plasma levodopa concentrations in healthy volunteers concomitantly receiving 25 mg of carbidopa and 100 mg of levodopa (Sinemet 25–100) and to assess the tolerability and safety of this combination. Placebo or tolcapone at doses of 5, 10, 25, 50, 100, 200, 400, and 800 mg was coadministered orally with Sinemet 25–100. Each dose was tested in a crossover fashion in a new group of six participants who each received active drug on one occasion and placebo on the other. Tolcapone increased the area under the plasma concentration-time curve and half-life of levodopa approximately twofold, without appreciably increasing the peak concentration. The maximum effect on levodopa half-life was observed with the 200-mg dose. Adverse effects were minor at all doses.

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0362-5664    

出版商:OVID    

年代:1997

数据来源: OVID