COMPUTER-ASSISTED MODELING OF THE PICROTOXININ AND GAMMA-BUTYROLACTONE RECEPTOR-SITE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 23  (2) , 511-518
Abstract
Three-dimensional models of the picrotoxinin [from plants of the Menispermaceae family] and alkyl-substituted .gamma.-butyrolactone (GBL) receptor sites were constructed with the aid of a molecular graphics computer system (MMS-X). These 2 independently derived models proved to be very compatible, which suggested that both types of compounds share a common site of action. Since picrotoxinin acts at GABA-regulated chloride channels, a hypothesis was made and tested that the convulsant GBL and picrotoxinin analogs physically impede the passage of Cl- through the channel. It was theoretically possible for the anticonvulsant GBL to act at this same site without blocking chloride [in mice]. The model was applied to several convulsant and anticonvulsant compounds of different chemical classes and was of somewhat general applicability.