Palmitic acid analogues exhibiting antinociceptive activity in mice.
Three palmitic acid derivatives were synthesized and evaluated as a potential platform for antinociceptive drug development. Female Swiss Webster mice were given N-(4-Methoxy-2-nitrophenyl)hexadecanamide (1), 2-amino-3-(palmitoylamino)benzoic acid (2) or 4-amino-3-(palmi-toylamino)benzoic acid (3) orally in doses of 10-100 mg/kg. The animals were tested for nociception using the hot plate and abdominal constriction response (writhing) tests. Compound 1 generated a dose-dependent antinociceptive effect, reflected by longer latencies (paw-lick and escape responses) and a decrease in writhing. Morphine (1.5-6 mg/kg, p.o.) and diclofenac (10-100 mg/kg, p.o.) were used as positive controls, respectively. Compounds 2 and 3 were less active in both nociceptive tests. The antinociception provoked by compound 1 was partially blocked by naloxone (1 mg/kg, i.p.) suggesting that this pharmacological effect could be due to the activation of micro-opioid receptors. N-(4-Methoxy-2-nitrophenyl)hexadecanamide showed antinociceptive effects in both nociceptive tests suggesting the possibility that this compound may define a new type of antinociceptive.
Déciga-Campos
Myrna
M
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, México. myrnadeciga@hotmail.com
Montiel-Ruiz
Rosa Mariana
RM
Navarrete-Vázquez
Gabriel
G
López-Muñoz
Francisco Javier
FJ
D019342:Acetic Acid; D000700:Analgesics; D000701:Analgesics, Opioid / Q000494:pharmacology; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
C530398:2-amino-3-(palmitoylamino)benzoic acid; C530399:4-amino-3-(palmitoylamino)benzoic acid; D000700:Analgesics; D000701:Analgesics, Opioid; D000814:Aniline Compounds; D000894:Anti-Inflammatory Agents, Non-Steroidal; C530397:N-(4-methoxy-2-nitrophenyl)hexadecanamide; D009292:Narcotic Antagonists; D010168:Palmitates; D062367:ortho-Aminobenzoates; D004008:Diclofenac; D009270:Naloxone; D009020:Morphine; D019342:Acetic Acid