Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Preclinical validation of mGlu2 PAMs in alcohol use disorder

Award Number: U43AA031388
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2026

Group Awards By:

View Award Description

Preclinical validation of mGlu2 PAMs in alcohol use disorder - PROJECT SUMMARY Alcohol Use Disorder (AUD) continues to be a significant problem, affecting 28.3 million adults in the United States, and is the third leading preventable cause of death. Disulfiram, naltrexone, and acamprosate are the only drugs approved by the Food and Drug Administration, but all three have limited efficacy and several contraindications. Given the substantial burden on society and the economy ($249 billion in 2010), there is a clear unmet need for effective and well-tolerated therapies that reduce alcohol dependence and relapse in AUD patients. AUD is characterized by phases of binge drinking, intoxication, and negative emotional states during withdrawal. The anticipation of alcohol leads to a repetition of these phases followed by periods of extended abstinence and frequent relapse. Importantly, each of these phases is accompanied by sleep disturbances (SDs). Three primary brain regions are involved in AUD-associated behavior: the prefrontal cortex (anticipation), basal ganglia (binge drinking), and amygdala (withdrawal). Several neurotransmitters are dysregulated in AUD, including the glutamatergic system. Extensive experimental evidence suggests that glutamate (Glu) critically modulates the actions of drugs of misuse, including alcohol. Therefore, normalization of aberrant Glu activity caused by chronic alcohol use potentially represents a novel therapeutic strategy to prevent relapse in AUD. The activation of metabotropic Glu receptor subtypes 2 and 3 (mGlu2/3) using agonists or positive allosteric modulators (PAMs) decreases ethanol (EtOH) self-administration (SA) as well as cue-induced reinstatement of EtOH seeking in rodents. Both alcohol-dependent rodents and humans show downregulation of mGlu2 expression, and many studies suggest that deficiencies in mGlu2 signaling may underlie AUD pathology. Moreover, preclinical studies indicate that mGlu2/3 activation has promise for treating stress- and anxiety-related disorders in humans and can systematically augment sleep, symptoms that are comorbid with AUD. We hypothesize that mGlu2 PAMs represent a promising new class of drugs to treat AUD. To test this hypothesis, our team has discovered and optimized three small molecule mGlu2 PAMs, SBP-9330, SBP-1315, and SBP-9220, that show efficacy in multiple models of substance-use disorders. To accomplish this, our specific aims are (1) Determine the in vivo efficacy of mGlu2 PAMs to decrease EtOH intake in rat models of dependent and non-dependent EtOH SA, (2) Determine the in vivo efficacy of mGlu2 PAMs to normalize SDs during withdrawal and abstinence following EtOH SA, and (3) Determine the effect of a fixed dose of EtOH on the PK profile and maximum tolerated dose of mGlu2 PAMs in rats. We have assembled a multidisciplinary team of investigators with the expertise and experience to achieve these outcomes. Successful completion of these studies will facilitate the development of a novel mGlu2 PAM towards filing of an investigational new drug (IND) application and ultimately, a safe and effective treatment for AUD.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	CAMINO PHARMA LLC	7161 ROCK VALLEY CT	SAN DIEGO	CA	92122	SAN DIEGO	USA	Alcohol Research Programs	001	2	8/11/2025	NON-COMPETING CONTINUATION	$0
2025	2024	CAMINO PHARMA LLC	7161 ROCK VALLEY CT	SAN DIEGO	CA	92122	SAN DIEGO	USA	Alcohol Research Programs	000	2	1/9/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $994,906 )
2024	2024	CAMINO PHARMA LLC	7161 ROCK VALLEY CT	SAN DIEGO	CA	92122	SAN DIEGO	USA	Alcohol Research Programs	001	2	7/30/2024	NON-COMPETING CONTINUATION	$994,906
2024	2023	CAMINO PHARMA, LLC	7161 ROCK VALLEY CT	SAN DIEGO	CA	92122	SAN DIEGO	USA	Alcohol Research Programs	000	1	10/26/2023	NEW	$0
														Subtotal = $994,906

Issue Date FY: 2023 ( Subtotal = $973,938 )
2023	2023	CAMINO PHARMA, LLC	7161 ROCK VALLEY CT	SAN DIEGO	CA	92122	SAN DIEGO	USA	Alcohol Research Programs	000	1	9/20/2023	NEW	$973,938
														Subtotal = $973,938

Grand Total All Awards = $1,968,844

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Preclinical validation of mGlu2 PAMs in alcohol use disorder

Award Number: U43AA031388

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer