Cns Drugs
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This review describes the medical, research and recreational uses of ketamine, an anaesthetic derivative of phencyclidine that has dissociative, analgesic and psychedelic properties. Ketamine has a complex mechanism of action that is further complicated by stereoselectivity; however, antagonism of glutamate NDMA receptors is thought to underlie its analgesic, dissociative and neuroprotective effects. While ketamine use in medical and veterinary settings is well documented and has a good safety record, the increase in its unregulated use outside of such controlled environments is a cause for concern. ⋯ The perceptual and mood changes observed in those who have consumed ketamine are highly sensitive to age, dose, route of administration, previous experience and setting. At low doses, stimulant effects predominate and the effect of environmental conditions are significant; with higher doses, psychedelic effects predominate and the effect of the environment diminishes. The potential of ketamine as a novel clinical and research tool is matched by its abuse potential outside medical settings.
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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.