Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the brain the extracellular concentration of glutamate is controlled by glial transporters that restrict the neurotransmitter action to synaptic sites and avoid excitotoxicity. Impaired transport of glutamate occurs in many cases of amyotrophic lateral sclerosis, a devastating motoneuron disease. Motoneurons of the brainstem nucleus hypoglossus are among the most vulnerable, giving early symptoms like slurred speech and dysphagia. However, the direct consequences of extracellular glutamate build-up, due to uptake block, on synaptic transmission and survival of hypoglossal motoneurons remain unclear and have been studied using the neonatal rat brainstem slice preparation as a model. Patch clamp recording from hypoglossal motoneurons showed that, in about one-third of these cells, inhibition of glutamate transport with the selective blocker dl-threo-beta-benzyloxyaspartate (TBOA; 50 mum) unexpectedly led to the emergence of rhythmic bursting consisting of inward currents of long duration with superimposed fast oscillations and synaptic events. Synaptic inhibition block facilitated bursting. Bursts had a reversal potential near 0 mV, and were blocked by tetrodotoxin, the gap junction blocker carbenoxolone, or antagonists of AMPA, NMDA or mGluR1 glutamate receptors. Intracellular Ca(2+) imaging showed bursts as synchronous discharges among motoneurons. Synergy of activation of distinct classes of glutamate receptor plus gap junctions were therefore essential for bursting. Ablating the lateral reticular formation preserved bursting, suggesting independence from propagated network activity within the brainstem. TBOA significantly increased the number of dead motoneurons, an effect prevented by the same agents that suppressed bursting. Bursting thus represents a novel hallmark of motoneuron dysfunction triggered by glutamate uptake block.
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PMID:Glutamate uptake block triggers deadly rhythmic bursting of neonatal rat hypoglossal motoneurons. 1645 92

Asenapine sublingual is a novel atypical antipsychotic approved in August 2009 for the acute treatment of schizophrenia, as well as for manic or mixed episodes as part of adult bipolar I disorder. Asenapine's in vitro profile is similar to other atypical antipsychotic agents insofar as there is higher affinity for serotonin 5-HT(2A) versus dopamine D(2) receptors. Asenapine exhibits a unique effect on monoamine, histamine and muscarinic receptor affinities, as well as effects on NMDA and AMPA receptors. This pharmacodynamic signature may mediate its symptom relief in positive, negative and mood symptoms, as well as conferring upon this agent an improved tolerability and safety profile when compared with some atypical agents. Asenapine has a relatively low propensity for changes in metabolic parameters, body composition, sedation/somnolence and extrapyramidal side effects, and is not associated with prolactin elevation or clinically significant electrocardiographic changes. Asenapine is available only in sublingual formulation, which has advantages (e.g., patient acceptance, compliance, difficulty swallowing) as well as disadvantages (i.e., patients are encouraged not to eat or drink within 10 min of administration). Its efficacy in mania is unequivocally established as is the sustaining of its acute antimanic effect. Its antidepressant and recurrence prevention effects in bipolar disorder are under investigation, as is its possible role in major depressive disorder.
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PMID:Pharmacology and efficacy of asenapine for manic and mixed states in adults with bipolar disorder. 2042 Apr 86