Taken together, these findings suggest that different signalling molecules may underlie the convulsive effects of the δ-receptor relative to its antihyperalgesic and antidepressant-like effects.

Rationale VRP26 displays mu opioid receptor agonist and delta opioid receptor antagonist activity in vitro, a pharmacological profile purported to produce reduced tolerance, dependence, and rewarding effects. We hypothesized that VRP26 would display reduced adverse effects after chronic administration as compared with the traditional opioid analgesic fentanyl. Objective To explore the development of tolerance, dependence and conditioned place preference of VRP26 as compared with the traditional opioid analgesic fentanyl. Methods The antinociceptive effects of VRP26 and fentanyl were assessed using the mouse warm water tail withdrawal (WWTW) assay. Measurement of antinociceptive tolerance and physical dependence occurred after seven days of continuous administration of either fentanyl (0.3 mg/kg/day) or VRP26 (10 mg/kg/day); tolerance was measured by a shift in the antinociceptive dose response curve in the WWTW assay. Physical dependence was determined by observation of withdrawal symptoms after precipitated withdrawal. Rewarding effects were measured by the ability of VRP26 or fentanyl to produce conditioned place preference. Results Fentanyl produced significant tolerance and dependence, as well as significant conditioned place preference. VRP26 produced neither tolerance nor physical dependence, nor did it produce significant conditioned place preference. Conclusions These results suggest that chronic treatment with VRP26 may produce less tolerance or physical dependence than chronic treatment with clinically available mu opioid analgesics such as fentanyl. Additionally, VRP26 produces less rewarding effects than fentanyl. This desirable in vivo profile may be due to the mixed efficacy nature of VRP26 and could provide the framework for safer opioid analgesics.

Background Sudden unexpected infant death (SUID) accounts for ~ 3400 deaths per year in the USA, and minimal progress has been made in reducing SUID over the past two decades. SUID is the sudden death of an infant that has occurred as a result of accidental suffocation in a sleeping environment, SIDS (sudden infant death syndrome), or from an unknown cause of death. Nationally, non-Hispanic Black (NHB) infants have twice the risk of SUID compared to non-Hispanic White (NHW) infants. In Chicago, this disparity is greatly magnified. To explore whether this disparity is similarly seen in other large cities, we analyzed SUIDs by race and ethnicity for a seven-year period from the 10 most populous US cities. SUID case counts by race and ethnicity were obtained for 2011–2017 from the 10 most populous US cities based on 2010 census data. For each city, we calculated average annual SUID rates (per 1000 live births) by race and ethnicity, allowing calculation of disparity rate ratios. Findings Nationally, from 2011 through 2017, there were 0.891 SUIDs per 1000 live births, with a rate of 0.847 for NHWs, 1.795 for NHBs, and 0.522 for Hispanics. In most study cities, the NHB and Hispanic SUID rates were higher than the corresponding national rate. Hispanic SUID rates were higher than NHW rates in 9 of the 10 largest cities. In every study city, the NHW SUID rate was lower than the national NHW rate. In Chicago, NHB infants had a SUID rate 12.735 times that of NHW infants. Conclusion With few exceptions, the 10 largest US cities had higher NHB and Hispanic SUID rates, but lower NHW SUID rates, compared to the corresponding rates at the national level. Unlike the national pattern, Hispanic SUID rates were higher than NHW rates in 9 of the 10 largest cities. Prevention is currently hampered by the lack of detailed, accurate, and timely information regarding the circumstances of these tragic deaths. A national SUID surveillance system would allow greater understanding of the factors that lead to this disproportionately distributed and enduring cause of infant death.