The palmitoylethanolamide and oleamide enigmas : are these two fatty acid amides cannabimimetic?
Lambert DM, Di Marzo V
Unité de chimie pharmaceutique et de Radiopharmacie, Ecole de Pharmacie, Universite catholique de Louvain, 73, avenue Emmanuel Mounier, Brussels, B-1200, Belgium.
Palmitoylethanolamide (PEA) and oleamide are two fatty acid amides which
1) share some cannabimimetic actions with delta9-tetrahydrocannabinol,
anandamide and 2-arachidonoylglycerol, and 2) may interact with proteins
involved in the biosynthesis, action and inactivation of endocannabinoids.
Due to its pharmacological actions and its accumulation in damaged cells,
PEA may have a physio-pathological role as an analgesic, anti-oxidant and
anti-inflammatory mediator. However, its mechanism of action is puzzling.
In fact, PEA does not bind to CB1 and CB2 receptors transfected into host
cells, but might be a ligand for a putative CBn receptor present in the
RBL-2H3 cell line. On the other hand, the analgesic effect of PEA is reversed
by SR144528, a CB2 antagonist. PEA may act as an entourage compound for
endocannabinoids, i.e. it may enhance their action for example by inhibiting
their inactivation. Oleamide is a sleep inducing lipid whose mechanism
of action is far from being understood. Although it does not bind with
high affinity to CB1 or CB2 receptors, it exhibits some cannabimimetic
actions which could be explained at least in part by entourage effects.
It is likely that oleamide and anandamide have common as well as distinct
pathways of action. The 5-HT2A receptor appears to be a target for oleamide
but the possibility of the existence of specific receptors for this compound
is open. The biosynthesis and tissue distribution of oleamide remain to
be assessed in order to both substantiate its role as a sleep-inducing
factor and investigate its participation in other physiopathological situations.
Publication Types:
Review
Review, academic
PMID: 10469890, UI: 99401111