Gambierol is a marine polycyclic ether toxin which is produced by the dinoflagellate Gambierdiscus toxicus.

The toxins are accumulated in fish through the food chain and can therefore cause human intoxication.

The symptoms of the toxicity resemble those of ciguatoxins, which are extremely potent neurotoxins that bind to voltage-sensitive sodium channels and alter their function.

[4][5] Different structural analogues were synthesized to determine which groups and side chains attached to the gambierol are essential for its toxicity.

Not only the fused polycyclic ether core is essential, but also the triene side chain at C51 and the C48-C49 double bond were indispensable.

[3][6] The synthesis of gambierol consists of two tetracyclic precursor molecules, one alcohol and one acetic acid, that fuse together.

[9] It acts as an intermembrane anchor where it displaces lipids and prohibits the voltage sensor domain of the channel from moving during physiologically important changes.

[12] If the Kv channels are closed, the depolarized membrane cannot repolarize to its resting state, causing a permanent action potential.

In neurons, gambierol has been reported to induce Ca2+ oscillations because of blockage of the voltage-gated potassium channels.

[15] The compounds are very lipophilic and will therefore diffuse to multiple organs and tissues, for example the liver, fat and the brain.

Gambierol is a potent blocker of potassium channels, which for a part determine the membrane potential.

[17] Treatment with gambierol is not being used yet, because the compound is toxic and also blocks other channels and thereby disrupts important processes.

Intake of gambierol can also cause pain, because Kv1.1 and Kv1.4 channels are blocked and that increases the excitability of central circuits.

[2] Gambierol is also an interesting compound in research into treatments of pathologies like Alzheimer's disease, which are caused by increased expression of β-amyloid and/or tau hyperphosphorylation.

[18][19] Gambierols function in inducing outgrowth of neurites in a bidirectional manner can potentially be used after neural injury.

Gambierol exhibits potent toxicity against mice at 50-80 μg/kg by intraperitoneal injection or 150 μg/kg when consumed orally.