High affinity for the rat brain sodium channel of newly discovered hydroxybenzoate saxitoxin analogues from the dinoflagellate Gymnodinium catenatum.
The paralytic shellfish poison family has been recently extended by the discovery of several analogues possessing a hydoxybenzoate moiety instead of the carbamoyl group one finds in saxitoxin, the parent molecule of this toxin family. We have investigated the potency of these new analogues on a representative isoform of the pharmacological target of these toxins, the voltage gated sodium channel. These toxins were found to have K1's in the low nanomolar range, only slightly less potent than saxitoxin. The hydroxybenzoate group may increase the lipophilicity of these toxins and improve their ability to pass through epithelia and therefore its uptake and elimination in both intoxication victims and animals that bioaccumulate paralytic shellfish toxins.
Llewellyn
Lyndon
L
Australian Institute of Marine Science, Marine Biotechnology, PMB 3, Townsville, MC 4810, Australia. l.llewellyn@aims.gov.au
Negri
Andrew
A
Quilliam
Michael
M
D000818:Animals; D001921:Brain / Q000378:metabolism; D004141:Dinoflagellida; D062385:Hydroxybenzoates / Q000493:pharmacokinetics*; D008387:Marine Toxins / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D012530:Saxitoxin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D026941:Sodium Channel Blockers / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000378:metabolism*
D062385:Hydroxybenzoates; D008387:Marine Toxins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012530:Saxitoxin