AEAAnandamide (N-arachidonoylethanolamine)

Formula

C₂₂H₃₇NO₂

Molar mass

347.53 g·mol⁻¹

CAS

94421-68-8

PubChem CID

5281969

First described

1992

Origin

Endocannabinoid

InChIKey

LGEQQWMQCRIYKG-DOFZRALJSA-N

Editorial estimate, not clinical.

The first endocannabinoid to be characterised, identified by William Devane, Lumír Hanuš and Raphael Mechoulam in 1992 (Science 258:1946) from pig brain. The name comes from the Sanskrit “ananda”, bliss. Anandamide is not stored - it is synthesised on demand on the cytosolic face of the neuronal membrane (NAPE-PLD hydrolyses an N-arachidonoyl-PE precursor) and degraded within minutes by FAAH (fatty acid amide hydrolase). Orthosteric affinity CB1 Ki ≈ 89 nM, CB2 Ki ≈ 371 nM - a partial agonist at both receptors. It is also an agonist at TRPV1 (which makes it both an endocannabinoid and an endovanilloid) and a substrate of several CYPs. It is anandamide, and its cousin 2-AG, that explain why the human brain responds to phytocannabinoids: we already carry the system. Endogenous concentrations ~10–60 pmol·g⁻¹ in the mammalian brain; they modulate the perception of pain, mood, appetite, short-term memory, the consolidation of REM sleep, inflammation and fertility. The clinical pharmacology of FAAH inhibition (URB597, PF-04457845) remains promising but suffered a historic setback with Bial's BIA 10-2474 trial (2016, Rennes) - another FAAH inhibitor, whose off-target toxicity caused one death and several neurological injuries.

Hydrolysed on demand from membrane N-arachidonoyl-PE (NAPE-PLD), degraded by FAAH (fatty acid amide hydrolase)

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

Class

Endocannabinoid

Origin

Endocannabinoid

Status

Endogenous

1. 1.Devane, Hanuš & Mechoulam - Science 1992PMID 1470919