N-(4-Methoxy-2-nitrophenyl)hexadecanamide, a palmitoylethanolamide analogue, reduces formalin-induced nociception.
OBJECTIVE
To investigate the local antinociceptive effect as well as the possible mechanisms of action of a novel analogue of palmitoylethanolamide (PEA) N-(4-methoxy-2-nitrophenyl)hexadecanamide (HD) in the rat formalin test.


METHODS
The formalin test was used to assess the antinociceptive activity of HD in vivo. The hydrolysis of anandamide catalyzed by fatty acid amide hydrolase (FAAH) was used to determine the action of HD on FAAH activity in vitro.


RESULTS
Local peripheral ipisilateral, but not contralateral, administration of HD (10-100μg/paw) produced a dose-dependent antinociceptive effect in rats. The CB(1) and CB(2) receptor antagonists AM281 (0.3-30μg/paw) and SR144528 (0.3-30μg/paw), respectively, reduced the antinociceptive effect of HD (100μg/paw). In addition, methiothepin (0.03-0.3μg/paw) and naloxone (5-50μg/paw) significantly reduced HD-induced antinociception (100μg/paw). In vitro, HD reduced only to a minor extent the hydrolysis of anandamide catalyzed by FAAH.


CONCLUSIONS
HD local administration produces antinociception that probably results from an indirect activation of peripheral CB(1) and CB(2) cannabinoid receptors. Data suggest that 5-HT(1) and opioid receptors also participate in the antinociceptive effect of this compound. HD may have potential as analgesic drug.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., Mexico.
José Eduardo
JE
Roa-Coria
Gabriel
G
Navarrete-Vázquez
Christopher J
CJ
Fowler
Francisco Javier
FJ
Flores-Murrieta
Myrna
M
Déciga-Campos
Vinicio
V
Granados-Soto
D000581:Amidohydrolases / Q000378:metabolism; D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000814:Aniline Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D005557:Formaldehyde; D006868:Hydrolysis; D008297:Male; D059225:Nociception / Q000187:drug effects*; D010168:Palmitates / Q000008:administration & dosage / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects* / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects / Q000378:metabolism; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000700:Analgesics; D000814:Aniline Compounds; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005557:Formaldehyde; D010168:Palmitates; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D011957:Receptors, Opioid; D044263:Receptors, Serotonin, 5-HT1; D000099252:Fatty Acid Amide Hydrolases; C530397:N-(4-methoxy-2-nitrophenyl)hexadecanamide; C078814:anandamide