N-(2-Hydroxyethyl)hexadecanamide is orally active in reducing edema formation and inflammatory hyperalgesia by down-modulating mast cell activation

Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide

“…Calignano et al, 1998;Jaggar et al, 1998; present study Ž and anti-inflammatory effects Benvenuti et al, 1968;Facci . et al, 1995;Mazzari et al, 1996 . Thus, drugs aimed at the putative palmitylethanolamide receptor might offer the advantage of combining these two complementary therapeutic properties.…”

“…three decades ago Bachur et al, 1965 , was shown to have Ž marked anti-inflammatory Benvenuti et al, 1968;Facci et . al., 1995;Mazzari et al, 1996 and antinociceptive effects Ž when administered as a drug Calignano et al, 1998;. Jaggar et al, 1998 Calignano et al, 1998Calignano et al, , 2000 .…”

Characterization of palmitoylethanolamide transport in mouse Neuro‐2a neuroblastoma and rat RBL‐2H3 basophilic leukaemia cells: comparison with anandamide

“…The mechanism appears to be mediated by a speci®c Na + -independent carrier protein in as much as it is saturable, temperature-dependent, selective, and apparently inhibited by various AEA analogues such as AM404 (for review, see Hillard & Jarrahian, 2000). The presence of a de®ned transport mechanism for PEA would provide an interesting pharmacological target for the treatment of in¯ammatory diseases, since a blockade of PEA transport would result in elevated extracellular concentrations of PEA, and hence, augmentation of the anti-in¯ammatory and anti-nociceptive e ects of this compound (Facci et al, 1995;Mazzari et al, 1996;Jaggar et al, 1998;Calignano et al, 1998). This would be analogous to the situation for AEA, where both the duration and intensity of the hypotensive e ects of i.v.…”

“…However, more recent data have indicated that PEA does not bind with high a nity to either of the two cannabinoid receptor subtypes (Showalter et al, 1996;antagonizing in¯ammatory processes (Facci et al, 1995;Mazzari et al, 1996). Furthermore, peripheral administration of PEA produces an analgesic e ect in formalin-induced in¯ammatory pain (Jaggar et al, 1998;Calignano et al, 1998), and the PEA-induced anti-nociceptive e ects are believed to be mediated by a peripheral CB 2 -like receptor.…”

Endocannabinoids inhibit release of nerve growth factor by inflammation-activated mast cells

“…In this paper, we describe the role of NGF released by noxious stimuli-activated mast cells in fuelling angiogenesis and, eventually, the modulating effects of the endocannabinoid PEA, an Nacylamidic molecule that negatively influences mast cell functions sustaining an inflammatory response [23]. 4 To demonstrate the hypothesized angiogenic potential of mast cells, we first challenged the one-of-a kind human cell line, derived from a patient with mast cell leukaemia, mastocytic cells HMC-1 [24] with inflammatory stimuli and then measured NGF released in the media.…”