| Title |
The Pharmacology of Imepitoin: The First Partial Benzodiazepine Receptor Agonist Developed for the Treatment of Epilepsy
|
|---|---|
| Published in |
CNS Drugs, December 2013
|
| DOI | 10.1007/s40263-013-0129-z |
| Pubmed ID | |
| Authors |
Chris Rundfeldt, Wolfgang Löscher |
| Abstract |
Although benzodiazepines (BZDs) offer a wide spectrum of antiepileptic activity against diverse types of epileptic seizures, their use in the treatment of epilepsy is limited because of adverse effects, loss of efficacy (tolerance), and development of physical and psychological dependence. BZDs act as positive allosteric modulators of the inhibitory neurotransmitter GABA by binding to the BZD recognition site ("BZD receptor") of the GABAA receptor. Traditional BZDs such as diazepam or clonazepam act as full agonists at this site, so that one strategy to resolve the disadvantages of these compounds would be the development of partial agonists with lower intrinsic efficacy at the BZD site of the GABAA receptor. Several BZD site partial or subtype selective compounds, including bretazenil, abecarnil, or alpidem, have been developed as anxioselective anxiolytic drugs, but epilepsy was not a target indication for such compounds. More recently, the imidazolone derivatives imepitoin (ELB138) and ELB139 were shown to act as low-affinity partial agonists at the BZD site of the GABAA receptor, and imepitoin was developed for the treatment of epilepsy. Imepitoin displayed a broad spectrum of anticonvulsant activity in diverse seizure and epilepsy models at tolerable doses, and, as expected from its mechanism of action, lacked tolerance and abuse liability in rodent and primate models. The more favorable pharmacokinetic profile of imepitoin in dogs versus humans led to the decision to develop imepitoin for the treatment of canine epilepsy. Based on randomized controlled trials that demonstrated antiepileptic efficacy and high tolerability and safety in epileptic dogs, the drug was recently approved for this indication in Europe. Hopefully, the favorable profile of imepitoin for the treatment of epilepsy in dogs will reactivate the interest in partial BZD site agonists as new treatments for human epilepsy. |
Mendeley readers
The data shown below were compiled from readership statistics for 112 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | <1% |
| Germany | 1 | <1% |
| Unknown | 110 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Other | 19 | 17% |
| Student > Bachelor | 15 | 13% |
| Student > Master | 14 | 13% |
| Researcher | 8 | 7% |
| Student > Postgraduate | 8 | 7% |
| Other | 23 | 21% |
| Unknown | 25 | 22% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 27 | 24% |
| Veterinary Science and Veterinary Medicine | 20 | 18% |
| Agricultural and Biological Sciences | 12 | 11% |
| Chemistry | 5 | 4% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 3% |
| Other | 17 | 15% |
| Unknown | 28 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 9. 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 06 May 2023.
All research outputs
#3,270,972
of 22,780,165 outputs
Outputs from CNS Drugs
#302
of 1,305 outputs
Outputs of similar age
#40,177
of 306,235 outputs
Outputs of similar age from CNS Drugs
#3
of 13 outputs
Altmetric has tracked 22,780,165 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,305 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has done well, scoring higher than 75% 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 306,235 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 86% of its contemporaries.
We're also able to compare this research output to 13 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.