Canadine, also known as (S)-tetrahydroberberine and xanthopuccine, is a benzylisoquinoline alkaloid (BIA), of the protoberberine structural subgroup, and is present in many plants from the family Papaveraceae, such as Corydalis yanhusuo and C. turtschaninovii.
Metabolically, (S)-canadine is derived from (S)-reticuline, a pivotal intermediate in the biosynthesis of numerous BIA structural subgroups, through three enzymatic steps: 1) berberine bridge enzyme to (S)-scoulerine; 2) (S)-scoulerine 9-O-methyltransferase to (S)-tetrahydrocolumbamine; and 3) (S)-canadine synthase/CYP719A21 to (S)-canadine.
(S)-Canadine is the immediate metabolic precursor of berberine, which is produced through the action of the enzyme tetrahydroberberine oxidase.
It is also an intermediate in the biosynthesis of noscapine, which is likewise a benzylisoquinoline alkaloid, but of the phthalideisoquinoline structural subgroup.
(S)-Canadine, berberine, palmatine, and hydrastine are the major alkaloids present in goldenseal. In Corydalis cava, the enzyme berberine reductase converts berberine back to canadine but as the (R) enantiomer of the product.
This type of inversion of stereochemistry allows both enantiomers of some alkaloids to be present in this species.
A number of in vitro effects of (S)-canadine have been reported. It stimulates myogenesis and inhibits muscle protein degradation. (S)-Canadine blocks K(ATP) channels in dopamine neurons. (S)-Canadine has displayed antioxidant activity: though it lacked any demonstrable cytotoxic effect in three unique cell cultures, it was observed to possess antioxidant activity against free radical-induced oxidative injury. (S)-Canadine can block voltage-dependent calcium channels, but at a level significantly lower than that of verapamil.
Canadine is also used in the synthesis of CPU 86017 (a novel Class III antiarrhythmic agent with multiple actions at ion channels).