Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1323099 (sympathomimetic)
 2,957 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitochondria are directly involved in cell survival and death. Drugs that protect mitochondria viability and prevent apoptotic cascade mechanisms involved in mitochondrial permeability transition pore (MPTp) will be cytoprotective. Rasagiline (N-propargyl-1R-aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO) B inhibitor, anti-Parkinson drug. Unlike selegiline, rasagiline is not derived from amphetamine, is not metabolized to neurotoxic l-methamphetamine derivative, nor does it have sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to L-dopa for patients with early and late Parkinson's disease (PD), and adverse events do not occur with greater frequency in subjects receiving rasagiline than those on placebo. Controlled studies indicate that it might have a disease-modifying effect in PD that may be related to neuroprotection. Its S-isomer, TVP1022, is a relatively inactive MAO inhibitor. However, both drugs have similar neuroprotective activities in neuronal cell cultures in response to various neurotoxins and in vivo (global ischemia, neurotrauma, head injury, anoxia, etc.), indicating that MAO inhibition is not a pre-requisite for neuroprotection. Structure activity studies have shown that the neuroprotective activity is associated with the propargyl moiety of rasagiline which protects mitochondrial viability and MPTp by activating Bcl-2 and protein kinase C (PKC), and down regulating pro-apoptotic FAS and Bax. Rasagiline and its derivatives also process amyloid precursor protein (APP) to the neuroprotective-neurotrophic soluble APP alpha (sAPPalpha) by PKC and MAP kinase-dependent activation of alpha-secretase. The neuroprotective activity of propargylamine has led us to develop novel bifunctional neuroprotective iron-chelating MAO-inhibiting drugs possessing propargyl moiety for the treatment of other neurodegenerative diseases.
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PMID:Mechanism of neuroprotective action of the anti-Parkinson drug rasagiline and its derivatives. 1585 Jun 77

Intracerebral hemorrhage (ICH) accounts for 10 to 15% of all strokes, but results in a disproportionately high morbidity and mortality. Although chronic hypertension accounts for the majority of ICH, other common causes include cerebral amyloid angiopathy, sympathomimetic drugs of abuse, and underlying cerebral vascular anomalies. Validated baseline predictors of clinical outcome after ICH include the Glasgow Coma Scale score, hematoma volume, presence and amount of intraventricular hemorrhage, infratentorial ICH location, and advanced age. Although no treatment of proven benefit currently exists for ICH, several recent large clinical trials have demonstrated the feasibility of surgical and medical treatments for ICH. Clinical research into ICH mechanisms of injury has demonstrated that hematoma expansion is common, even in patients without coagulopathy. Basic research has suggested that perihematoma injury is more likely related to toxicity of blood and iron in the brain ("neurohemoinflammation") rather than primary ischemic injury. Current guidelines for ICH treatment emphasize blood pressure management, urgent and rapid correction of coagulopathy, and surgery for cerebellar ICH. Ongoing clinical trials are investigating surgical evacuation of lobar hemorrhage, minimally invasive surgical hematoma evacuation, and aggressive blood pressure lowering.
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PMID:Intracerebral hemorrhage. 1911 72