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Discovery of New treatments for Drug Abuse

Award Number: R01DA007315
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/1991
PERIOD OF PERFORMANCE END DATE: 04/30/2021

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Discovery of New treatments for Drug Abuse - DESCRIPTION (provided by applicant): The aims of the proposal are in accord with the mission of the Addiction Treatment Discovery Program (ATDP): To discover potential pharmacological treatments for substance abuse in humans, with an emphasis on relapse prevention, through preclinical testing and evaluation of compounds. The principal goal of the project is to provide potential treatment agents for polydrug dependence by targeting single chemical entities that mimic the profile produced by a buprenorphine/naltrexone combination. There is evidence from both clinical and preclinical research that this combination can help prevent relapse to drug taking behaviour, including both opioids and cocaine. The target compounds lack of, or very limited, mu opioid receptor efficacy will render the compounds safe and ethically acceptable for use in both opioid using and non-opioid using addicts. Efficacy as treatment agents will also come from the compounds kappa opioid receptor antagonist activity, coupled with agonism at NOP (nociceptin) receptors and antagonism at delta opioid receptors. Lead compounds have been identified during the current funding period from within the orvinol and naltrexone series. These series have already produced several compounds of clinical or veterinary utility, including buprenorphine and naltrexone. Key, recent medicinal chemistry discoveries by our group including, 1) the role of a methyl group at C7 in the orvinol series in reducing efficacy at kappa receptors and increasing NOP activity and 2) the role of the C14 side chain in the naltrexone series in allowing substantial NOP activity to be introduced to this series of opioid antagonists, has allowed compounds with the desired profile to be developed. These discoveries will be extended; in particular, ligands from the orvinol series have been identified for further evaluation with one currently undergoing extensive in vivo testing and evaluation of its ADME-tox profile. Follow-on/back-up compounds are also being developed. The significance of this work is that it will tell us whether single compounds can be developed that can block relapse to both opioid and cocaine use, what types of relapse are blocked (drug-, stress- or cue-primed) and will allow us to move our identified candidate therapeutics closer to the clinic.


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: 2023 ( Subtotal = -$25,684 )
2023	2019	UNIVERSITY OF BATH	CLAVERTON DOWN	BATH				GBR	Drug Use and Addiction Research Programs	000	25	1/17/2023	NON-COMPETING CONTINUATION	-$25,684
														Subtotal = -$25,684

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2019	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON			GBR	Drug Use and Addiction Research Programs	000	25	12/1/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $365,574 )
2019	2019	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Drug Use and Addiction Research Programs	000	25	11/30/2018	NON-COMPETING CONTINUATION	$365,574
														Subtotal = $365,574

Issue Date FY: 2018 ( Subtotal = $365,574 )
2018	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Drug Use and Addiction Research Programs	001	24	4/26/2018	NON-COMPETING CONTINUATION	$36,558
2018	2018	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Drug Use and Addiction Research Programs	000	24	11/28/2017	NON-COMPETING CONTINUATION	$329,016
														Subtotal = $365,574

Issue Date FY: 2017 ( Subtotal = $365,574 )
2017	2017	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Drug Use and Addiction Research Programs	001	23	5/22/2017	NON-COMPETING CONTINUATION	$36,558
2017	2017	UNIVERSITY OF BATH	THE AVENUE	BATH	AVON	BA2 7AY		GBR	Drug Use and Addiction Research Programs	000	23	11/15/2016	NON-COMPETING CONTINUATION	$329,016
														Subtotal = $365,574

Issue Date FY: 2016 ( Subtotal = $361,918 )
2016	2016	University of Bath	Claverton Down	Bath				GBR	Drug Use and Addiction Research Programs	000	22	11/19/2015	NON-COMPETING CONTINUATION	$329,016
2016	2016	University of Bath	Claverton Down	Bath				GBR	Drug Use and Addiction Research Programs	001	22	3/8/2016	NON-COMPETING CONTINUATION	$32,902
														Subtotal = $361,918

Issue Date FY: 2015 ( Subtotal = $365,870 )
2015	2015	University of Bath	Claverton Down	Bath				GBR	Drug Use and Addiction Research Programs	001	21	3/13/2015	COMPETING CONTINUATION	-$365,870
2015	2015	University of Bath	Claverton Down	Bath				GBR	Drug Use and Addiction Research Programs	000	21	1/30/2015	COMPETING CONTINUATION	$365,870
2015	2015	University of Bath	Claverton Down	Bath				GBR	Drug Use and Addiction Research Programs	002	21	3/23/2015	COMPETING CONTINUATION	$365,870
														Subtotal = $365,870

Issue Date FY: 2012 ( Subtotal = $310,382 )
2012	2012	UNIVERSITY OF BATH	CLAVERTON DOWN BATH	BATH				GBR	Drug Use and Addiction Research Programs	000	20	7/11/2012	NON-COMPETING CONTINUATION	$310,382
														Subtotal = $310,382

Issue Date FY: 2011 ( Subtotal = $319,812 )
2011	2011	UNIVERSITY OF BATH	CLAVERTON DOWN BATH	BATH				GBR	Drug Use and Addiction Research Programs	000	19	7/29/2011	NON-COMPETING CONTINUATION	$319,812
														Subtotal = $319,812

Issue Date FY: 2010 ( Subtotal = $322,096 )
2010	2010	UNIVERSITY OF BATH	CLAVERTON DOWN BATH	BATH				GBR	Drug Use and Addiction Research Programs	001	18	7/15/2010	NON-COMPETING CONTINUATION	$322,096
2010	2009	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	17	6/8/2010	COMPETING CONTINUATION	$0
														Subtotal = $322,096

Issue Date FY: 2009 ( Subtotal = $327,349 )
2009	2009	UNIVERSITY OF BATH	CLAVERTON DOWN BATH	BATH				GBR	Drug Use and Addiction Research Programs	001	17	9/11/2009	COMPETING CONTINUATION	$327,349
2009	2008	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	16	9/11/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $327,349

Issue Date FY: 2007 ( Subtotal = $285,785 )
2007	2007	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	001	15	9/24/2007	SUPPLEMENT FOR EXPANSION	$41,040
2007	2007	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	15	8/1/2007	NON-COMPETING CONTINUATION	$244,745
														Subtotal = $285,785

Issue Date FY: 2006 ( Subtotal = $252,055 )
2006	2006	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	14	8/2/2006	NON-COMPETING CONTINUATION	$252,055
														Subtotal = $252,055

Issue Date FY: 2005 ( Subtotal = $216,000 )
2005	2005	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	13	9/23/2005	COMPETING CONTINUATION	$216,000
														Subtotal = $216,000

Issue Date FY: 2003 ( Subtotal = $200,000 )
2003	2003	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	12	6/16/2003	NON-COMPETING CONTINUATION	$200,000
														Subtotal = $200,000

Issue Date FY: 2002 ( Subtotal = $200,000 )
2002	2002	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	11	2/22/2002	NON-COMPETING CONTINUATION	$200,000
														Subtotal = $200,000

Issue Date FY: 2001 ( Subtotal = $200,000 )
2001	2001	UNIVERSITY OF BATH	**	BATH		00000		GBR	Drug Use and Addiction Research Programs	000	10	4/10/2001	COMPETING CONTINUATION	$200,000
														Subtotal = $200,000

Issue Date FY: 2000 ( Subtotal = $49,957 )
2000	2000	UNIVERSITY OF BRISTOL	24 TYNDALL AVENUE	BRISTOL BS8 1TQ		BS8 1		GBR	Drug Use and Addiction Research Programs	001	9	7/20/2000	SUPPLEMENT FOR EXPANSION	$49,957
														Subtotal = $49,957

Issue Date FY: 1999 ( Subtotal = $192,166 )
1999	1999	UNIVERSITY OF BRISTOL	24 TYNDALL AVENUE	BRISTOL BS8 1TQ		BS8 1		GBR	Drug Use and Addiction Research Programs	000	9	6/28/1999	NON-COMPETING CONTINUATION	$192,166
														Subtotal = $192,166

Issue Date FY: 1998 ( Subtotal = $214,826 )
1998	1998	UNIVERSITY OF BRISTOL	24 TYNDALL AVENUE	BRISTOL BS8 1TQ		BS8 1		GBR	Drug Use and Addiction Research Programs	000	8	6/24/1998	NON-COMPETING CONTINUATION	$188,905
1998	1998	UNIVERSITY OF BRISTOL	24 TYNDALL AVENUE	BRISTOL BS8 1TQ		BS8 1		GBR	Drug Use and Addiction Research Programs	001	7	12/23/1997	SUPPLEMENT FOR EXPANSION	$25,921
														Subtotal = $214,826

Grand Total All Awards = $4,889,254

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Discovery of New treatments for Drug Abuse

Award Number: R01DA007315

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/1991

PERIOD OF PERFORMANCE END DATE: 04/30/2021

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