A novel delta opioid receptor antagonist, SoRI-9409, produces a selective and long-lasting decrease in ethanol...

Area of Science:

• Neuroscience
• Pharmacology
• Addiction Research

Background:

• Naltrexone, a mu opioid receptor (MOP-R) agonist, reduces alcohol intake.
• SoRI-9409, a naltrexone derivative, exhibits higher affinity for delta opioid receptors (DOP-Rs).

Purpose of the Study:

• Investigate the effects of SoRI-9409 on ethanol consumption.
• Determine the impact of enhanced DOP-R efficacy on alcohol consumption reduction.

Main Methods:

• Administered SoRI-9409, naltrexone, and naltrindole to high- and low-ethanol-consuming rats.
• Measured ethanol consumption and DOP-R-stimulated [(35)S]GTP gamma S binding.
• Assessed SoRI-9409's effects on morphine analgesia, conditioned place preference, and anxiety.

Main Results:

• SoRI-9409 was threefold more effective than naltrexone or naltrindole in reducing ethanol consumption in high-drinking rats for up to 24 hours.
• Daily 28-day administration of SoRI-9409 continuously reduced ethanol intake, with lasting effects after cessation.
• SoRI-9409 inhibited DOP-R-stimulated [(35)S]GTP gamma S binding in brain membranes.

Conclusions:

• SoRI-9409 demonstrates selective and sustained reduction of ethanol consumption.
• Compounds targeting DOP-Rs, like SoRI-9409, show potential as novel therapeutics for alcoholism.