CAY10505 1218777-13-9 at 30 min postinjection. Antinociceptive effects of the lowest dose of AM1241 were notably absent at subsequent time points. Racemic AM1241 and CAY10505 1218777-13-9 AM1241 failed to produce an antinociceptive effect relative to the DMSO condition at 30 min postinjection. Both AM1241 and the enantiomers, AM1241 and AM1241, produced thermal antinociception in the plantar test at 30 min postinjection relative to the DMSO control condition. Only AM1241, produced an antinociceptive effect at 60 min postinjection. However, both AM1241 and AM1241 produced antinociception at 120 min postinjection for each comparison, whereas AM1241 failed to do so. The highest dose of AM1241 also produced antinociception relative to the vehicle condition at 30 min postinjection.

Antinociceptive effects of AM1241 were still present at 120 min postinjection. Antinociceptive effects of the highest dose of either AM1241 or AM1241 were notably absent at all time points. Pharmacological specificity was evaluated using doses of AM1241, AM1241, and AM1241 that produced maximal antinociception buy CAY10505 for all compounds. AM1241, AM1241, and AM1241 buy CAY10505 produced antinociception to thermal stimulation relative to baseline measurements. As expected, AM1241 produced thermal antinociception in the plantar test that was blocked by SR144528 but not by rimonabant at 30min postinjection. Antinociception produced by either AM1241 or AM1241 was blocked by SR144528, but not rimonabant, at the same time point.
Similar effects were observed for AM1241 at 120 min postinjection. However, ANOVA failed to reveal a reliable antinociceptive effect of AM1241 at 120 min postdrug.
Planned comparisons suggested that AM1241, administered either alone or together with rimonabant, produced antinociception at this time point relative to the vehicle condition. Rimonabant and SR144528 did not alter thermal paw withdrawal latencies relative to vehicle at either 30 or 120 min postinjection. Role of Opioid Receptors in Cannabinoid CB2 mediated To evaluate the contribution of peripheral opioid receptors to AM1241 induced antinociception, we employed a local dose of naloxone validated previously to block the antinociceptive effects of systemic AM1241 in otherwise naive rats.
Morphine produced naloxone sensitive peripheral antinociception in the plantar test at 30 min postinjection in our study, this effect was completely blocked by local injection of naloxone.
A peripheral site of action for this blockade was confirmed by the fact that thermal paw withdrawal latencies remained elevated, relative to baseline and vehicle treatment, in the noninjected paw following systemic morphine administration. Morphine produced antinociception relative to the DMSO condition at 120 min postinjection. However, at this time point, locally injected naloxone was no longer blocking morphine antinociception. Due to lack of efficacy of naloxone blockade at 120 min, data presented in Fig. 5 are restricted to the 30 min time point. The dose of naloxone which completely blocked the antinociceptive effects of morphine failed to block the antinociceptive effects of either AM1241 or AM1241. Moreover, naloxone and a fivefold higher dose failed to block the antinociceptive effects of AM1241 relative to vehicle treatment. Additionally, naloxone