Peripheral nervous system specific sodium channels, DNA encoding therefor, crystallization, X-ray diffraction, computer molecular modeling, rational drug design, drug screening, and methods of making and using thereof

Abstract

Cloning, expression, viral and delivery vectors and hosts which contain nucleic acid coding for at least one peripheral nervous system specific (PNS) sodium channel peptide (SCP), isolated PNS SCP, and compounds and compositions and methods, are provided, for isolating, crystallizing, x-ray analysing molecular modeling, rational drug designing, selecting, making and using therapeutic or diagnostic agents or ligands having at least one peripheral nervous system specific (PNS) sodium channel (SC) modulating activity.

1 - 16 . (Cancelled)  
     
     
         17 . A bioassay for assessing a candidate modulating agent of a PNS SCP, comprising: 
 (A) contacting a candidate agent with a cell line expressing in the cell membrane of said cell a PNS SCP; and    (B) evaluating the modulation of the SC biological activity of said cell mediated by said contacting of said candidate agent.    
     
     
         18 . A method according to  claim 17 , wherein said cell line is selected from PC12 cells or a recombinant form thereof comprising an isolated nucleic acid molecule, wherein the isolated nucleic acid molecule encodes a polypeptide monomer of a peripheral nervous system specific (PNS) sodium channel the monomer: (i) having an amino acid sequence that has at least 87% identity to the full amino acid sequence disclosed in SEQ ID NO:10 and (ii) forming a PNS type I voltage gated sodium channel sodium ions when the monomer is expressed in  Xenopus oocytes.    
     
     
         19 . A PNS SCP modulating agent, identified by a method according to  claim 17 .  
     
     
         20 . A PNS SCP modulating agent according to  claim 19 , wherein said agent is a methyl-phenylhalophenyl-substituted piperizine compound.  
     
     
         21 . A PNS SCP modulating agent according to  claim 20 , wherein said piperizine compound is lidoflazine (Merck Index Monograph 5311) or a derivative thereof.  
     
     
         22 - 39 . (Cancelled)