TY - JOUR
T1 - N-(4-Methoxy-2-nitrophenyl)hexadecanamide, a palmitoylethanolamide analogue, reduces formalin-induced nociception
AU - Roa-Coria, José Eduardo
AU - Navarrete-Vázquez, Gabriel
AU - Fowler, Christopher J.
AU - Flores-Murrieta, Francisco Javier
AU - Déciga-Campos, Myrna
AU - Granados-Soto, Vinicio
N1 - Funding Information:
This work was supported by the ESM-IPN (project SIP-20110653 to MD-C), the Swedish Science Research Council (grant no. 12158 , medicine, to CJF) and the Research Funds of the Medical Faculty, Umeå University (to CJF). The authors would like to thank Britt Jacobsson for technical assistance in the FAAH experiments. This study is part of the B.Sc. dissertation of José Eduardo Roa-Coria. During this work José Eduardo Roa-Coria received the “Apoyo para estudiantes de Licenciatura” fellowship from Conacyt. José Eduardo Roa-Coria is a Conacyt fellow.
PY - 2012/12/17
Y1 - 2012/12/17
N2 - Aims: 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. Main 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. Key findings: Local peripheral ipisilateral, but not contralateral, administration of HD (10-100 μg/paw) produced a dose-dependent antinociceptive effect in rats. The CB1 and CB2 receptor antagonists AM281 (0.3-30 μg/paw) and SR144528 (0.3-30 μg/paw), respectively, reduced the antinociceptive effect of HD (100 μg/paw). In addition, methiothepin (0.03-0.3 μg/paw) and naloxone (5-50 μg/paw) significantly reduced HD-induced antinociception (100 μg/paw). In vitro, HD reduced only to a minor extent the hydrolysis of anandamide catalyzed by FAAH. Significance: HD local administration produces antinociception that probably results from an indirect activation of peripheral CB1 and CB2 cannabinoid receptors. Data suggest that 5-HT1 and opioid receptors also participate in the antinociceptive effect of this compound. HD may have potential as analgesic drug.
AB - Aims: 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. Main 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. Key findings: Local peripheral ipisilateral, but not contralateral, administration of HD (10-100 μg/paw) produced a dose-dependent antinociceptive effect in rats. The CB1 and CB2 receptor antagonists AM281 (0.3-30 μg/paw) and SR144528 (0.3-30 μg/paw), respectively, reduced the antinociceptive effect of HD (100 μg/paw). In addition, methiothepin (0.03-0.3 μg/paw) and naloxone (5-50 μg/paw) significantly reduced HD-induced antinociception (100 μg/paw). In vitro, HD reduced only to a minor extent the hydrolysis of anandamide catalyzed by FAAH. Significance: HD local administration produces antinociception that probably results from an indirect activation of peripheral CB1 and CB2 cannabinoid receptors. Data suggest that 5-HT1 and opioid receptors also participate in the antinociceptive effect of this compound. HD may have potential as analgesic drug.
KW - Anandamide
KW - Antinociception
KW - Cannabinoid receptors
KW - Fatty acid amide hydrolase
KW - N-(4-Methoxy-2-nitrophenyl)hexadecanamide
KW - Palmitoylethanolamide
UR - http://www.scopus.com/inward/record.url?scp=84870301472&partnerID=8YFLogxK
U2 - 10.1016/j.lfs.2012.09.024
DO - 10.1016/j.lfs.2012.09.024
M3 - Artículo
C2 - 23069585
SN - 0024-3205
VL - 91
SP - 1288
EP - 1294
JO - Life Sciences
JF - Life Sciences
IS - 25-26
ER -