Brevetoxin derivatives that inhibit toxin activity.
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.
Purkerson-Parker
S L
SL
Neurotoxicology Division MD-74B, University of North Carolina Curriculum in Toxicology, United States Environmental Protection Agency, NC 27711, USA.
Fieber
L A
LA
Rein
K S
KS
Podona
T
T
Baden
D G
DG
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
D008387:Marine Toxins; D035964:Oxocins; D026941:Sodium Channel Blockers; C053342:brevetoxin; D000095702:Polyether Toxins