Robert R. Fenichel

 

Drugs that Do and Do Not Affect Cardiac Ion Channels

    The accompanying pages provide data that may be relevant to evaluation of drugs that affect cardiac ion channels.  

   The main table lists various drugs of interest, and in each line shows the IC50 (that is, the concentration of drug needed for half-complete effect) for some drug at some cell-membrane receptor or binding site. The drugs listed are a sample of opportunity, and drugs known to affect human ventricular repolarization (see http://www.torsades.org) are (not surprisingly) heavily represented.   The receptors noted are

  •      those through which the drug is thought to have its intended effect (e.g., for antihistamines,  the H1 histamine receptor); and

  •      those that are related to cardiac ion channels.

    Receptor-binding studies can give results that vary with the model system that is used, so one column of the table indicates the model system that was used.  Abbreviations used in the listings of the models include

AM

atrial myocytes

AT-1

mouse atrial tumor myocytes

COS

African green monkey kidney

GP LM

guinea-pig ileal longitudinal smooth muscle

HEK

human embryonic kidney

HERG

human ether-a-go-go-related gene, associated with IKr

PF

Purkinje fibers

VM

ventricular myocytes

XO

Xenopus oocytes

   

   Disturbance of any of the cardiac ion channels could theoretically lead to arrhythmias, but the channel most clearly associated with arrhythmias is IKr, the rapidly-activating delayed-rectifier potassium current.  In each row of the table, one column shows the drug’s relative potency at the IKr receptor compared to its potency at the receptor described elsewhere in the row.  For example, one antihistamine (chlorpheniramine) is 10000 times more potent at its intended receptor (H1) than it is at IKr, while another (terfenadine) is several times more potent at IKr than at H1.

 

   To facilitate navigation through this large (and growing) table, links are provided so that the user can sort it by drug class, by drug name, by the potency ratio described in the last paragraph, by receptor and then by drug name, by receptor and then by potency, or by receptor and then by model.

 

   An auxiliary table (linked through the drug names) provides information as to drugs’ therapeutic concentrations.  Another auxiliary table provides a reference list to show the sources of the data; codes in some of the citations are unique identifiers for MedLine (MLUI) or PubMed (PMUI).

 

   Most of the data in the table were gathered over the years by ,  but his employer did not permit him to serve the public by publishing.  Other contributions came from , , , and , and most of the MLUIs and PMUIs were provided by .   I had missed a bug in the computer-generated HTML of the tables, but it was spotted by Ruben Venegas of ChemBridge Corporation.  Useful formatting suggestions were provided by Tom Papoian.  Other contributors to the project are welcome, and will be acknowledged.

 

  I have data that are not presented here.  These other data are proprietary, or were submitted pre-publication on the condition that they not be released.  The contributors of these other data should from time to time ask themselves if it has become appropriate to allow these data to appear in the Web-published tables.

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Page revised: 11/29/2010 21:48