Cns Drugs
-
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.
-
Neuraxial drug administration describes techniques that deliver drugs in close proximity to the spinal cord, i.e. intrathecally into the CSF or epidurally into the fatty tissues surrounding the dura, by injection or infusion. This approach was initially developed in the form of spinal anaesthesia over 100 years ago. Since then, neuraxial drug administration has evolved and now includes a wide range of techniques to administer a large number of different drugs to provide anaesthesia, but also analgesia and treatment of spasticity in a variety of acute and chronic settings. ⋯ Beside these established approaches, a wide range of other drugs have been assessed for neuraxial administration to provide analgesia; however, most are in various early stages of investigation and are not used routinely. These drugs include neostigmine, ketamine, midazolam and adenosine, and the conotoxin ziconotide. The latter is possibly the most unusual compound here; it has recently gained registration for intrathecal use in specific chronic pain conditions.