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 μ-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.