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Substrate-selective inhibition of COX-2 to target affective disorders

Award Number: R01MH100096
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2013
PERIOD OF PERFORMANCE END DATE: 05/31/2019

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Substrate-selective inhibition of COX-2 to target affective disorders - DESCRIPTION (provided by applicant): Mood and anxiety disorders exert substantial societal cost and personal burden for patients and families. Current treatment approaches for these disorders are primarily focused on increasing brain neurotransmitters like serotonin, i.e. via selective serotonin-reuptake inhibitors (SSRIs). However, large-scale effectiveness studies have demonstrated this class of drugs is only partially effective. Recent studies have suggested that elevating levels of endogenous brain cannabinoids could exert therapeutic benefit in mood and anxiety disorders including PTSD. We have recently developed novel inhibitors of cyclooxygenase-2 (COX-2) that selectively prevent inactivation of brain endocannabinoids without preventing synthesis of prostaglandins; which are inflammatory mediators required for normal immune and vascular function. Given that long-term inhibition of prostaglandin synthesis is associated with gastrointestinal and cardiovascular toxicity, development, validation, and preclinical evaluation of novel pharmacological strategies to modulate COX-2 activity to enhance endocannabinoid signaling without affecting prostaglandin synthesis is a high research priority. We will test the hypothesis that "substrate-selective" inhibitors of COX-2 selectively increase brain endocannabinoid levels without affecting prostaglandin levels and that they exert preclinical efficacy in models of mood and anxiety disorders. Completion of these studies will provide preclinical evidence for the efficacy of a novel class of antidepressant and anxiolytic drugs, and could validate COX-2 as a viable molecular target for future drug discovery directed at the treatment of affective disorders.


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: 2019 ( Subtotal = $0 )
2019	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	7	9/6/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $395,000 )
2018	2018	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	7	5/15/2018	NON-COMPETING CONTINUATION	$395,000
														Subtotal = $395,000

Issue Date FY: 2017 ( Subtotal = $395,000 )
2017	2017	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	002	6	5/19/2017	NON-COMPETING CONTINUATION	$395,000
2017	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	5	11/8/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$97,354
2017	2015	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Mental Health Research Grants	000	3	11/8/2016	NON-COMPETING CONTINUATION	-$97,354
														Subtotal = $395,000

Issue Date FY: 2016 ( Subtotal = $397,240 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	4	5/21/2016	EXTENSION WITH OR WITHOUT FUNDS	$390,000
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	002	4	6/30/2016	EXTENSION WITH OR WITHOUT FUNDS	$0
2016	2016	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	003	5	6/30/2016	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$397,240
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	001	4	6/24/2016	EXTENSION WITH OR WITHOUT FUNDS	-$390,000
														Subtotal = $397,240

Issue Date FY: 2015 ( Subtotal = $390,000 )
2015	2015	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	3	7/7/2015	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2014 ( Subtotal = $390,000 )
2014	2014	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	2	6/26/2014	NON-COMPETING CONTINUATION	$390,000
														Subtotal = $390,000

Issue Date FY: 2013 ( Subtotal = $390,000 )
2013	2013	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Mental Health Research Grants	000	1	4/15/2013	NEW	$390,000
														Subtotal = $390,000

Grand Total All Awards = $2,357,240

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Substrate-selective inhibition of COX-2 to target affective disorders

Award Number: R01MH100096

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2013

PERIOD OF PERFORMANCE END DATE: 05/31/2019

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