In 2003, the EFNS Task Force was set up for putting forth guidelines for the management of the Restless Legs Syndrome (RLS) and the Periodic Limb Movement Disorder (PLMD). After determining the objectives for management and the search strategy for primary and secondary RLS and for PLMD, a review of the scientific literature up to 2004 was performed for the drug classes and interventions employed in treatment (drugs acting on the adrenoreceptor, antiepileptic drugs, benzodiazepines/ hypnotics, dopaminergic agents, opioids, other treatments). Previous guidelines were consulted. All trials were analysed according to class of evidence, and recommendations formed according to the 2004 EFNS criteria for rating. Dopaminergic agents came out as having the best evidence for efficacy in primary RLS. Reported adverse events were usually mild and reversible; augmentation was a feature with dopaminergic agents. No controlled trials were available for RLS in children and for RLS during pregnancy. The following level A recommendations can be offered: for primary RLS, cabergoline, gabapentin, pergolide, ropinirole, levodopa and rotigotine by transdermal delivery (the latter two for short-term use) are effective in relieving the symptoms. Transdermal oestradiol is ineffective for PLMD.
It has been previously demonstrated that gabapentin, a gamma-amino butyric acid analogue, inhibits monoaminergic neurotransmitter release from rabbit caudate nucleus slices and from rat cortex. In humans this drug has been shown to have anti-epileptogenic activity. Serotonin may act as an inhibitory neurotransmitter and its interaction with blood platelets is thought to reflect its central actions. We investigated sleep stages, whole blood serotonin levels, and serum melatonin in healthy men after the administration of gabapentin. With increasing serum gabapentin levels six healthy subjects showed an increase in sleep stages 3 and 4 and in whole blood serotonin (P less than 0.05) Serum melatonin levels were not influenced. On account of these results we speculate that gabapentin modulates the release of serotonin from blood platelets. The increase in peripheral serotonin points paradigmatically to an increase in the bioavailability of serotonin which may account for the increase in sleep stages 3 and 4.
The pharmacokinetics and the endocrine profile of a new low molecular somatostatin derivative, SMS 201\p=n-\995, were investigated in a group of 35 normal subjects. Clearance studies (n = 6) for this peptide showed a prolonged half-life in plasma, 113 min, following single sc injections of 50 or 100 \ g=m\ g. Arginine stimulation tests (n = 6) were conducted immediately and 180 min after sc injection of 50 \ g=m\ g of SMS 201\p=n-\995. The stimulatory effect of arginine on GH and insulin was counteracted by the peptide at the P < 0.001 and P < 0.02 significance level, respectively. Delayed arginine stimulation revealed a persistent blockade of the GH release (P < 0.02), whereas a recovery of the insulin response was observed. Plasma
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