PT  - JOURNAL ARTICLE
AU  - W E Klunk
AU  - B L Kalman
AU  - J A Ferrendelli
AU  - D F Covey
TI  - Computer-assisted modeling of the picrotoxinin and gamma-butyrolactone receptor site.
DP  - 1983 Mar 01
TA  - Molecular Pharmacology
PG  - 511--518
VI  - 23
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/23/2/511.short
4100  - http://molpharm.aspetjournals.org/content/23/2/511.full
SO  - Mol Pharmacol1983 Mar 01; 23
AB  - Three-dimensional models of the picrotoxinin and alkyl-substituted gamma-butyrolactone (GBL) receptor sites were constructed with the aid of a molecular graphics computer system (MMS-X). These two independently derived models proved to be very compatible, which suggested that both types of compounds share a common site of action. Since picrotoxinin is known to act at gamma-aminobutyric acid-regulated chloride channels, a hypothesis was made and tested that the convulsant GBL and picrotoxinin analogues physically impede the passage of chloride ions through the channel. It was also shown that it was theoretically possible for the anticonvulsant GBLs to act at this same site without blocking chloride flux. Finally, the model was applied to several convulsant and anticonvulsant compounds of different chemical classes and was found to be of somewhat general applicability.