Cns Drugs
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gamma-Hydroxybutyrate (GHB) is an endogenous short chain fatty acid and a, mostly oral, pharmacological compound that has been utilised in a variety of ways. Endogenously, GHB is synthesised locally within the CNS, mostly from its parent compound GABA. Sodium oxybate is the sodium salt of GHB and is used for the exogenous oral administration of GHB. ⋯ In narcolepsy, sodium oxybate has shown dose-related effects on various properties of sleep, including increases in slow-wave sleep duration and delta power, and a reduced number of night-time awakenings. Furthermore, multiple measures of daytime sleepiness and cataplexy demonstrated consistent short- and long-term improvement in response to night-time sodium oxybate therapy. The most common reported adverse events include dose-related headache, nausea, dizziness and somnolence.
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Randomized Controlled Trial Multicenter Study
Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of menstrual migraine.
To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral tablet as an acute treatment for menstrual migraine attacks. ⋯ Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.
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Mitochondrial encephalomyopathies are a multisystemic group of disorders that are characterised by a wide range of biochemical and genetic mitochondrial defects and variable modes of inheritance. Among this group of disorders, the mitochondrial myopathy, encephalopathy, lactic acidosis with stroke-like episodes (MELAS) syndrome is one of the most frequently occurring, maternally inherited mitochondrial disorders. As the name implies, stroke-like episodes are the defining feature of the MELAS syndrome, often occurring before the age of 15 years. ⋯ Currently, no consensus criteria exist for treating the MELAS syndrome or mitochondrial dysfunction in other diseases. Many of the therapeutic strategies used have been adopted as the result of isolated case reports or limited clinical studies that have included a heterogeneous population of patients with the MELAS syndrome, other defects in oxidative phosphorylation or lactic acidosis due to disorders of pyruvate metabolism. Current approaches to the treatment of the MELAS syndrome are based on the use of antioxidants, respiratory chain substrates and cofactors in the form of vitamins; however, no consistent benefits have been observed with these treatments.
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Genetic and experimental evidence points to amyloid-beta (Abeta) peptide as the culprit in Alzheimer's disease pathogenesis. This protein fragment abnormally accumulates in the brain cortex and hippocampus of patients with Alzheimer's disease, and self-aggregates to form toxic oligomers causing neurodegeneration. Abeta is heterogeneous and produced from a precursor protein (amyloid precursor protein [APP]) by two sequential proteolytic cleavages that involve beta- and gamma-secretases. ⋯ The finding that some NSAID analogues preferentially inhibit the formation of Abeta(42) over Abeta(40) and do not affect Notch processing has opened a new therapeutic window. The progress in design of selective inhibitors as well as recent results obtained in animal studies prove that gamma-secretase remains among the best targets for the therapeutic control of amyloid build-up in Alzheimer's disease. The full understanding of gamma-secretase regulation may yet uncover new therapeutic leads.
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Neostigmine is a parasympathomimetic agent that has been recently investigated for use as an adjunct analgesic agent in the perioperative and peripartum period. A number of studies have investigated the intrathecal, epidural, caudal and intra-articular routes of administration of this agent, as well as the addition of neostigmine to local anaesthetics used for brachial plexus block and intravenous regional anaesthesia. While the intrathecal administration of neostigmine produced useful analgesic effects in the postoperative period in some studies, the high incidence of adverse events, mainly nausea and vomiting, limit the clinical usefulness of this route of administration. ⋯ Intra-articular administration of neostigmine 500microg produced a useful analgesic effect in the postoperative period in several studies and was not associated with an increase in the incidence of adverse effects. Studies investigating the efficacy of adding neostigmine to the local anaesthetics used for brachial plexus block and intravenous regional anaesthesia reported conflicting results. Further studies are required to determine the place of the administration of neostigmine by these routes.