Effects of the delta opioid receptor agonist KNT-127 on electroencephalographic activity in mice

Background: We previously reported that the novel selective delta opioid receptor (DOP) agonist KNT-127 did not cause convulsions in mice, whereas the prototype DOP agonist SNC80 did. Previous studies have reported that SNC80 caused electroencephalographic (EEG) disturbances in rodents. However, whether KNT-127 affects EEG responses is unknown. Therefore, the present study aimed to compare the effect of KNT-127 on EEG responses with that of SNC80 in mice.

Methods: For behavioral experiments, male C57BL6/J mice were injected intraperitoneally with either KNT-127 (30 mg/kg) or SNC80 (30 mg/kg) and monitored for convulsions and subsequent catalepsy-like behavior for 10 min immediately after drug treatment. For EEG recording experiments, EEG electrodes were implanted into the right hemisphere. EEG signals exceeding twice the baseline amplitude were defined as seizure spikes.

Results: KNT-127 did not induce convulsive or catalepsy-like behaviors in mice and did not result in seizure spikes, while significantly higher EEG power density was observed at 2 Hz. In contrast, SNC80 administration resulted in convulsive behaviors, seizure spikes, and significantly higher EEG power density between 2 and 10 Hz in mice.

Conclusions: In this study, we clearly demonstrated that KNT-127 administration induces neither convulsive effects nor seizure spikes in mice. We propose that KNT-127 should be considered a candidate compound for the development of improved DOP-based psychotropic drug that lack the convulsive properties.