摘要:

Extracts ofHypericum perforatumL. (St John’s wort) are now successfully competing for status as a standard antidepressant therapy. Because of this, great effort has been devoted to identifying the active antidepressant compounds in the extract. From a phytochemical point of view, St John’s wort is one of the best-investigated medicinal plants. A series of bioactive compounds has been detected in the crude material, namely flavonol derivatives, biflavones, proanthocyanidines, xanthones, phloroglucinols and naphthodianthrones.Although St John’s wort has been subjected to extensive scientific studies in the last decade, there are still many open questions about its pharmacology and mechanism of action. Initial biochemical studies reported that St John’s wort is only a weak inhibitor of monoamine oxidase-A and -B activity but that it inhibits the synaptosomal uptake of serotonin, dopamine and noradrenaline (norepinephrine) with approximately equal affinity. However, otherin vitrobinding assays carried out using St John’s wort extract demonstrated significant affinity for adenosine, GABAA, GABABand glutamate receptors.In vivoSt John’s wort extract leads to a downregulation of β-adrenergic receptors and an upregulation of serotonin 5-HT2receptors in the rat frontal cortex and causes changes in neurotransmitter concentrations in brain areas that are implicated in depression. In studies using the rat forced swimming test, an animal model of depression, St John’s wort extracts induced a significant reduction of immobility. In other experimental models of depression, including acute and chronic forms of escape deficit induced by stressors, St John’s wort extract was shown to protect rats from the consequences of unavoidable stress. Recent neuroendocrine studies suggest that St John’s wort is involved in the regulation of genes that control hypothalamic-pituitary-adrenal axis function. With regard to the antidepressant effects of St John’s wort extract, many of the pharmacological activities appear to be attributable to the naphthodianthrone hypericin, the phloroglucinol derivative hyperforin and several flavonoids.This review integrates new findings of possible mechanisms that may underlie the antidepressant action of St John’s wort and its active constituents with a large body of existing literature.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The assessment of brain volume changes on serial magnetic resonance imaging (MRI) scans can provide an objective measure of the neurodegenerative component of multiple sclerosis (MS) pathology. Results from placebo-controlled and crossover clinical trials indicate that immunomodulating (e.g. recombinant interferon-β [IFNβ]-1a [Rebif®1]and IFNβ-1b [Betaferon®] and glatiramer acetate [Copaxone®]) and immunosuppressive (e.g. cladribine and alemtuzumab) treatments for relapsing-remitting (RR) and secondary progressive MS lack substantial efficacy in preventing the development of brain atrophy, despite the marked effects of these treatments on clinical and MRI outcomes of disease activity. A modest but significant treatment effect on brain atrophy has been reported for patients with RRMS only in one trial of IFNβ-1a (Avonex®) and in another study of long-term corticosteroid therapy.Failure to find a significant treatment benefit in preventing brain atrophy might be the result of inadequate trial designs, including their relatively short durations, which may not be adequate to reveal beneficial effects in a chronic disease like MS. Alternatively, such a failure might indicate that treatments proven to be effective in reducing MS-related inflammation are unable to act with the same efficacy on the most severe and disabling pathological substrates of the disease. The modest correlation between MRI enhancement frequency and brain atrophy observed in the placebo groups of several trials also fits with the concept that the suppression of inflammatory activity in MS is not fully and rapidly associated with a similar effect on the global neurodegenerative process of the disease.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

Neurocysticercosis is a common cause of neurological disease in developing countries and a major cause of epilepsy worldwide. A unique characteristic of human neurocysticercosis is that the living parasite is very well tolerated in human brain, so symptoms and clinical disease primarily result from death of the organism and accompanying inflammatory reaction in the human CNS. Among the diverse clinical manifestations of human neurocysticercosis, seizures are the most common, but other clinical problems occur, depending upon the localisation and viability of the parasite.Although both praziquantel and albendazole are effective agents, there is controversy about their role in several forms of the disease. Systematic reviews have pointed out the limited quality of available data on therapy. At a recent international conference convened to develop guidelines for treatment of this disease, areas of consensus and disagreement on the role of antiparasitic therapy were discussed. It was clear to all that cysticercosis cannot be regarded as a single disorder; treatment needs to be modified based on the location and number of cysticerci and the host response. There was a strong consensus that there is no role for antiparasitic drugs in patients with only calcified lesions. Studies suggest that patients with single enhancing lesions will do well regardless of antiparasitic therapy. Antiparasitic drugs are contraindicated in patients with cerebral oedema (cysticercal encephalitis). Most experts strongly recommend antiparasitic therapy in patients with multiple subarachnoid cysticerci or giant cysticerci. In patients with ventricular cysticerci, endoscopic removal is the preferred therapy. However, recent evidence suggests that placement of a ventricular shunt followed by antiparasitic therapy is an acceptable alternative. Standard treatment for localization-related epilepsy is effective for seizures caused by cysticercosis. In general, seizures are easily controlled in this illness.While many controversies regarding the treatment of patients with neurocysticercosis were not resolved at the international consensus conference, participants did conclude that controlled prospective studies are required to define optimal therapy for the infection and that treatment of infected individuals must be individualised.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The aetiology of sleep disturbances in patients with Parkinson’s disease is multifactorial. Medications, the disease process and underlying sleep disorders may contribute to sleepiness in patients with the disease. Somnolence, excessive daytime sleepiness and sleep attacks appear to be more common in patients with Parkinson’s disease who are treated with dopamine receptor agonists than in those who are treated with other antiparkinsonian agents, although virtually all dopaminergic antiparkinsonian medications may contribute to sleepiness. Somnolence caused by dopamine agonists may be dose related and occurs most frequently during the dose-escalation phase. Somnolence may also emerge or worsen after a period of time on a stable dose. Patients with Parkinson’s disease and caregivers should be informed about the risk of sleepiness and sleep attacks associated with dopaminergic medications and the potential implications for driving safety.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS

摘要:

The management of neurological and psychiatric disorders is a vast and evolving area for researchers, primary care physicians and specialists. To help you keep up to date with the latest advances worldwide on all aspects of drug therapy for neurological and psychiatric disorders, this section of the journal brings you information selected from the drug therapy reporting serviceInpharma Weekly1. The following reports are selected from the latest issues, summarising the most important research and development news, clinical studies, treatment guidelines, pharmacological, pharmacoeconomic and adverse drug reactions/interactions news, and expert opinion pieces published across a broad range of literature sources.

ISSN:1172-7047    

出版商:ADIS    

年代:2003

数据来源: ADIS