Computer-assisted modeling of the picrotoxinin and γ-butyrolactone receptor site

W. E. Klunk, B. L. Kalman, J. A. Ferrendelli, D. F. Covey

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


Three-dimensional models of the picrotoxinin and alkyl-substituted γ-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 γ-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.

Original languageEnglish
Pages (from-to)511-518
Number of pages8
JournalMolecular pharmacology
Issue number2
StatePublished - 1983


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