| Title |
Effects of Antipsychotic Drugs on Ito, INa, Isus, IK1, and hERG: QT Prolongation, Structure Activity Relationship, and Network Analysis
|
|---|---|
| Published in |
Pharmaceutical Research, May 2006
|
| DOI | 10.1007/s11095-006-0070-7 |
| Pubmed ID | |
| Authors |
William J. Crumb, Sean Ekins, R. Dustan Sarazan, James H. Wikel, Steven A. Wrighton, Christopher Carlson, Charles M. Beasley |
| Abstract |
To evaluate in vitro and computationally model the effects of selected antipsychotic drugs on several ionic currents that contribute to changes in the action potential in cardiac tissue. Fourteen antipsychotic drugs or metabolites were examined to determine whether QT interval prolongation could be accounted for by an effect on one or more myocardial ion channels [I(to), I(Na), I(sus), I(K1), and human ether-a-go-go related gene (hERG)]. Using the patch clamp technique, drug effects on these human cardiac currents were tested. All molecules had little inhibitory effect on ion channels (blocking at concentrations >5 microM) other than hERG. A significant correlation was observed between the estimated hERG blockade and the increase in corrected QT for five of the antipsychotics. Molecular modeling identified hydrophobic features related to the interaction with hERG and correctly rank-ordered the test set molecules olanzapine and its metabolites. A network analysis of ligand and protein interactions around hERG using MetaCore (GeneGo Inc., St. Joseph, MI, USA) was used to visualize antipsychotics with affinity for this channel and their interactions with other proteins in this database. The antipsychotics do not inhibit the ion channels I(to), I(Na), I(sus), I(K1) to any appreciable extent; however, blockade of hERG is a likely mechanism for the prolongation of the QT interval. |
Mendeley readers
The data shown below were compiled from readership statistics for 60 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 1 | 2% |
| Netherlands | 1 | 2% |
| United States | 1 | 2% |
| Unknown | 57 | 95% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 16 | 27% |
| Other | 10 | 17% |
| Professor > Associate Professor | 8 | 13% |
| Student > Bachelor | 7 | 12% |
| Student > Ph. D. Student | 4 | 7% |
| Other | 11 | 18% |
| Unknown | 4 | 7% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 19 | 32% |
| Chemistry | 9 | 15% |
| Agricultural and Biological Sciences | 8 | 13% |
| Pharmacology, Toxicology and Pharmaceutical Science | 6 | 10% |
| Biochemistry, Genetics and Molecular Biology | 3 | 5% |
| Other | 7 | 12% |
| Unknown | 8 | 13% |
Attention Score in Context
This research output has an Altmetric Attention Score of 5. 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 01 February 2016.
All research outputs
#5,894,231
of 22,842,950 outputs
Outputs from Pharmaceutical Research
#886
of 2,857 outputs
Outputs of similar age
#19,476
of 65,924 outputs
Outputs of similar age from Pharmaceutical Research
#15
of 34 outputs
Altmetric has tracked 22,842,950 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 2,857 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.0. This one has gotten more attention than average, scoring higher than 68% 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 65,924 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 69% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.