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. α-Naphthoyl-PbTx-3 acted as a PbTx-3 antagonist but did not affect Na+ channels that were not exposed to PbTx-3. β-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.
Original language | English (US) |
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Pages (from-to) | 385-393 |
Number of pages | 9 |
Journal | Chemistry and Biology |
Volume | 7 |
Issue number | 6 |
DOIs | |
State | Published - Jun 1 2000 |
Externally published | Yes |
Keywords
- Brevetoxin antagonists
- Brevetoxins
- Marine neurotoxins
- Sodium channel
ASJC Scopus subject areas
- Organic Chemistry