Unveiling the antinociceptive mechanisms of Methyl-2-(4-chloro-phenyl)-5-benzoxazoleacetate: insights from nociceptive assays in mice.

OBJECTIVE: Methyl-2-(4-chloro- phenyl)-5-benzoxazoleacetate (MCBA), a synthetic benzoxazole derivative with established antipsoriatic efficacy, was investigated for potential antinociceptive effects. This study employs various nociceptive assays in mice to elucidate MCBA's antinociceptive mechanisms. MATERIALS AND METHODS: MCBA's antinociceptive potential was tested against various nociception models induced by formalin, glutamate, capsaicin, a transient receptor potential vanilloid 1 (TRPV1) receptor agonist, and phorbol 12-myristate 13-acetate, a protein kinase C (PKC) activator. It was then assessed using the hot plate test and examined within the acetic acid-induced writhing test. During the acetic acid-induced writhing test, MCBA was pre-challenged against selective receptor antagonists such as naloxone, caffeine, atropine, yohimbine, ondansetron, and haloperidol. It was also pre-challenged with ATP-sensitive potassium channel inhibitor (glibenclamide) to further elucidate its antinociceptive mechanism. RESULTS: The results showed that oral administration of MCBA led to a dose-dependent and significant inhibition (p < 0.05) of nociceptive effects across all evaluated models at doses of 60, 120, and 240 mg/kg. Moreover, the efficacy of MCBA's antinociceptive potential was significantly counteracted (p < 0.0001) by specific antagonists: (i) directed at adenosinergic, alpha-2 adrenergic, and cholinergic receptors using caffeine, yohimbine, and atropine, respectively; and (ii) targeting ATP-sensitive potassium channels, employing glibenclamide. Antagonists aimed at opioidergic and serotoninergic receptors (naloxone and ondansetron, respectively) had poor utility in inhibiting antinociceptive activity. Conversely, the dopaminergic receptor antagonist haloperidol potentiated locomotor abnormalities associated with MCBA treatment. CONCLUSIONS: MCBA-induced antinociception involves modulation of glutamatergic-, TRVP1 receptors- and PKC-signaling pathways. It impacts adenosinergic, alpha-2 adrenergic, and cholinergic receptors and opens ATP-sensitive potassium channels.

N-Acetyltransferase-2 (NAT2) genotype frequency among Jordanian volunteers.

OBJECTIVE: To determine the frequency of major NAT2 alleles and genotypes among the Jordanian population. METHODS: DNA samples from 150 healthy Jordanian volunteers were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism assays (PCR-RFLP) to determine the frequency of four major alleles: NAT2*4, NAT2*5, NAT2*6 and NAT2*7. RESULTS: The frequency (95% confidence interval) of NAT2*4, NAT2*5, NAT2*6 and NAT2*7 alleles was 0.247 (0.198 - 0.296), 0.373 (0.318 - 0.428), 0.347. 0.293 - 0.401) and 0.033 (0.013 - 0.053), respectively. The most prevalent genotypes are those which encode slow acetylation phenotype. Around 58.7%, 33.3% and 8% of volunteers carried the slow, the intermediate and the fast-encoding genotypes, respectively. CONCLUSION: NAT2 genotype profile among Jordanians is similar to Caucasians. However, NAT2*6 allele is slightly high in comparison with Arab Middle Eastern populations.