title: Brevetoxin derivatives that inhibit toxin activity.
abstract: BACKGROUND
  The brevetoxins are marine neurotoxins that interfere with the normal functions of the voltage-gated Na(+) channel. We have identified two brevetoxin derivatives that do not exhibit pharmacological properties typical of the brevetoxins and that function as brevetoxin antagonists.
  
  
  RESULTS
  PbTx-3 and benzoyl-PbTx-3 elicited Na(+) channel openings during steady-state depolarizations; however, two PbTx-3 derivatives retained their ability to bind to the receptor, but did not elicit Na(+) channel openings. alpha-Naphthoyl-PbTx-3 acted as a PbTx-3 antagonist but did not affect Na(+) channels that were not exposed to PbTx-3. beta-Naphthoyl-PbTx-3 reduced openings of Na(+) channels that were not exposed to PbTx-3.
  
  
  CONCLUSIONS
  Some modifications to the brevetoxin molecule do not alter either the binding properties or the activity of these toxins. Larger modifications to the K-ring sidechain do not interfere with binding but have profound effects on their pharmacological properties. This implies a critical function for the K-ring sidechain of the native toxin.
authors.affiliation: Neurotoxicology Division MD-74B, University of North Carolina Curriculum in Toxicology, United States Environmental Protection Agency, NC 27711, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Purkerson-Parker
authors.forename: L A
authors.initials: LA
authors.lastname: Fieber
authors.forename: K S
authors.initials: KS
authors.lastname: Rein
authors.forename: T
authors.initials: T
authors.lastname: Podona
authors.forename: D G
authors.initials: DG
authors.lastname: Baden
mesh_terms: D000818:Animals; D002460:Cell Line; D008297:Male; D008387:Marine Toxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D035964:Oxocins; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D000095702:Polyether Toxins
chemical_list: D008387:Marine Toxins; D035964:Oxocins; D026941:Sodium Channel Blockers; C053342:brevetoxin; D000095702:Polyether Toxins