| Title |
Molecular Targets for Antiepileptic Drug Development
|
|---|---|
| Published in |
Neurotherapeutics, January 2007
|
| DOI | 10.1016/j.nurt.2006.11.010 |
| Pubmed ID | |
| Authors |
Brian S. Meldrum, Michael A. Rogawski |
| Abstract |
This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the alpha subunits of voltage-gated Na+ channels and also T-type voltage-gated Ca2+ channels) or influence GABA-mediated inhibition. Recently, alpha2-delta voltage-gated Ca2+ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na+ channels and GABA(A) receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca2+ channel subunits and auxiliary proteins, A- or M-type voltage-gated K+ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA(B) and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current Ih; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na+ channels underlying persistent Na+ currents or GABA(A) receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies. |
Mendeley readers
The data shown below were compiled from readership statistics for 315 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 2 | <1% |
| Norway | 1 | <1% |
| Italy | 1 | <1% |
| Germany | 1 | <1% |
| United Kingdom | 1 | <1% |
| Peru | 1 | <1% |
| Mexico | 1 | <1% |
| Austria | 1 | <1% |
| Romania | 1 | <1% |
| Other | 3 | <1% |
| Unknown | 302 | 96% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 67 | 21% |
| Researcher | 51 | 16% |
| Student > Bachelor | 37 | 12% |
| Student > Master | 25 | 8% |
| Professor > Associate Professor | 22 | 7% |
| Other | 74 | 23% |
| Unknown | 39 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 69 | 22% |
| Medicine and Dentistry | 52 | 17% |
| Neuroscience | 43 | 14% |
| Pharmacology, Toxicology and Pharmaceutical Science | 30 | 10% |
| Chemistry | 29 | 9% |
| Other | 37 | 12% |
| Unknown | 55 | 17% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 October 2020.
All research outputs
#5,447,195
of 25,374,917 outputs
Outputs from Neurotherapeutics
#570
of 1,307 outputs
Outputs of similar age
#23,034
of 168,348 outputs
Outputs of similar age from Neurotherapeutics
#5
of 15 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. Compared to these this one has done well and is in the 75th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,307 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 168,348 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 80% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.