In addition to their function in trafficking, TARPs alter the biophysical properties of AMPA receptors in remarkable ways and
thus contribute significantly to the functional plasticity of the synapse. The study of TARP-mediated functional plasticity of AMPA receptors, which has emerged only recently as a hot new field, promises to yield valuable insight into the regulation of neuronal communication. (C) click here 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Ampa receptors mediate the majority of excitatory synaptic transmission in the brain. Thus, the mechanisms that control the developmental and activity-dependent changes in the functional synaptic expression of AMPA receptors are of fundamental importance. Here we focus on the role of GluR2 subunit in synaptic function and plasticity. (C) 2009 IBRO.
Published by Elsevier Ltd. All rights reserved.”
“Background Calcitonin gene-related peptide (CGRP) probably has a role in migraine pathophysiology, and antagonism of its receptors might provide treatment without the vasoconstrictor effects of triptans. We aimed to assess the clinical profile of MK-0974 (telcagepant), an orally bioavailable antagonist of CGRP receptor.
Methods In a randomised, parallel-treatment, placebo-controlled, double-blind, trial at 81 sites in the Europe and the USA, adults with migraine diagnosed by International Headache Society criteria treated moderate or severe attacks with either oral telcagepant selleckchem selleck kinase inhibitor 1.50 mg or 300 mg, zolmitriptan 5 mg, or placebo. The five co-primary endpoints were pain freedom, pain relief, or absence of photophobia, phonophobia, or nausea at 2 h after treatment. Analysis was by the full analysis set and multiplicity was controlled for with a step-down closed-testing procedure. This trial is registered with ClinicalTrials.gov, number NCT00442936.
Findings
1380 patients were randomly assigned to receive telcagepant 150 mg (n=333) or 300 mg (354), zolmitriptan (345), or placebo (348). Telcagepant 300 mg was more effective than placebo for pain freedom (95 [27%] of 353 patients vs 33 [10%] of 343 [p<0.0001]), pain relief (194 [55%] of 353 vs 95 [28%] of 343 [p<0.0001]), and absences of phonophobia(204[58%] of 353 vs 126 [37% of 342 [p<0.0001.]), photophobia (180 [51%] of 353 vs 99 [29%] of 342 [p<0.0001]), and nausea (229 [65%] of 352 vs 1.89 [55%] of 342 [p=0.0061]). Efficacy of telcagepant 300 mg and zolmitriptan 5 mg were much the same, and both were more effective than telcagepant 150 mg. Adverse events were recorded for 31% taking telcagepant 1.50 mg, 37% taking telcagepant 300 mg, 51% taking zolmitriptan 5 mg, and 32% taking placebo.
Interpretation Telcagepant 300 mg is effective as an acute treatment for migraine with efficacy comparable to that of zolmitriptan 5 mg, but with fewer associated adverse effects.
Funding Merck Research Laboratories.