YangonineYangonin

Formula

C₁₅H₁₄O₄

Molar mass

258.09 g·mol⁻¹

CAS

500-62-9

PubChem CID

5281575

Origin

A natural product of plant origin, present in the roots of Piper methysticum and in a few other species. It does not come from cannabis and does not belong to the phytocannabinoids; its connection to the endocannabinoid system rests on its affinity for the CB1 receptor, not on its botanical origin.

InChIKey

XLHIYUYCSMZCCC-VMPITWQZSA-N

Editorial estimate, not clinical.

Yangonin connects two pharmacologies that are not spontaneously brought together. Kava, prepared from the roots of Piper methysticum, has been consumed for centuries in the Pacific for its relaxing and social effects, and its active principles, the kavalactones, are traditionally linked to an action on ion channels and on GABAergic transmission. Ligresti and colleagues asked a different question in 2012: do these molecules touch the endocannabinoid system? The screen covered five natural kavalactones and nine synthetic analogues, tested for their affinity at cannabinoid receptors and for their ability to inhibit the two major endocannabinoid-degrading enzymes. The result is clear and narrow. A single molecule stands out, yangonin, with an inhibition constant of 0.72 micromolar at the human CB1 receptor and a distinct selectivity with respect to CB2, whose constant exceeds 10 micromolar. None of the compounds tested significantly inhibits fatty acid amide hydrolase or monoacylglycerol lipase. The authors draw two consequences. The first is pharmacological: the endocannabinoid system could contribute to the complex human psychopharmacology of kava and of the anxiolytic preparations derived from it, which followed from no earlier hypothesis. The second is chemical: the kavalactone skeleton, a pyranone linked by an ethylenic bridge to a methoxylated aromatic ring, offers a synthetically accessible scaffold unrelated to the classical cannabinoids, which makes it an interesting starting point for designing new ligands.

A plant polyketide biosynthetic route leading to the kavalactone skeleton: a six-membered unsaturated pyranone lactone bearing a methoxy group and linked through an ethylenic bridge to a methoxyphenyl ring. That architecture, entirely different from the terpenophenolic skeleton of the cannabis cannabinoids, explains the interest of the compound as a chemical starting scaffold for designing new cannabinoid ligands.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

ECS modulator (research)

Origin

A natural product of plant origin, present in the roots of Piper methysticum and in a few other species. It does not come from cannabis and does not belong to the phytocannabinoids; its connection to the endocannabinoid system rests on its affinity for the CB1 receptor, not on its botanical origin.

Status

Unscheduled

1. 1.Ligresti et coll. 2012 : kavalactones et système endocannabinoïde, la yangonine d'origine végétale est un nouveau ligand du récepteur CB1PMID 22525682