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New Drugs to Enhance Endocannabinoid Responses for Treating Excitotoxicity, Phase

Award Number: R44DA023737
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2007
PERIOD OF PERFORMANCE END DATE: 11/30/2014

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New Drugs to Enhance Endocannabinoid Responses for Treating Excitotoxicity, Phase - DESCRIPTION (provided by applicant): There is a vital need for effective treatments against seizure-related brain damage and other events of excitotoxic neurodegeneration. Recurring seizures can result from epilepsy, brain trauma, developmental disorders, exposure to toxins, military-threat agents, and drugs of abuse (including prenatal exposure). Seizure-induced damage involves the same excitotoxic over-activation of glutamate receptors as occurs in stroke and traumatic brain injury. The resulting brain damage can cause devastating neurological, cognitive, and neuropsychiatric problems. With the need to find better therapeutic avenues, this proposal will further develop drugs to enhance the neuroprotective activation of the endocannabinoid system that occurs in response to excitotoxic insults including seizures. Compensatory synthesis and release of endogenous anandamide have been linked to excitotoxic protection in the brain. Our SBIR Phase-I work identified novel inhibitors of the endocannabinoid-hydrolyzing enzyme fatty acid amide hydrolase (FAAH) that effectively reduced seizure severity as well as the associated brain damage and behavioral deficits, even when administered several hours post-insult. This Phase-II proposal will continue to take advantage of the convenient KA rat model of seizure induction in order to facilitate the timely assessment of new, "drugable" FAAH inhibitor analogs with improved physicochemical and pharmacological profiles. The overall goal is to generate one potential candidate and three back-ups as selective, potent, and safe neuroprotectants for development as first-in-class drugs for treating seizure-related damage and other types of excitotoxic insults that cause long-term neurological impairment. PUBLIC HEALTH RELEVANCE: Successful development of medications to treat diseases whose etiology involves excitotoxic brain injury and its symptoms (particularly, seizures) will satisfy pressing medical needs for various disorders (stroke; Alzheimer's, Huntington's, and Parkinson's diseases; amyotrophic lateral sclerosis) for which extant therapies offer marginal value. Drugs of abuse may act as neurotoxicants and incite excitotoxic brain injury and seizures, and their neurodegenerative effects can adversely affect the developing fetus in utero. The latter is of particular importance to NIDA's mission. Our overall goal is to generate one potential development candidate and three back-ups to address the therapeutic needs of these 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: 2014 ( Subtotal = $0 )
2014	2011	MAKSCIENTIFIC LLC	PO BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	000	3	11/14/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2013 ( Subtotal = $0 )
2013	2011	MAKSCIENTIFIC LLC	PO BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	000	3	11/9/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2011 ( Subtotal = $516,628 )
2011	2011	MAKSCIENTIFIC LLC	P.O. BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	000	3	1/6/2011	NON-COMPETING CONTINUATION	$516,628
														Subtotal = $516,628

Issue Date FY: 2010 ( Subtotal = $0 )
2010	2009	MAKSCIENTIFIC LLC	PO BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	000	2	2/24/2010	COMPETING CONTINUATION	$0
2010	2009	MAKSCIENTIFIC LLC	PO BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	001	2	8/23/2010	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $489,260 )
2009	2009	MAKSCIENTIFIC LLC	P.O. BOX 184	WEST MYSTIC	CT	06388	SOUTHEASTERN CT	USA	Drug Use and Addiction Research Programs	000	2	8/4/2009	COMPETING CONTINUATION	$489,260
														Subtotal = $489,260

Grand Total All Awards = $1,005,888

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New Drugs to Enhance Endocannabinoid Responses for Treating Excitotoxicity, Phase

Award Number: R44DA023737

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2007

PERIOD OF PERFORMANCE END DATE: 11/30/2014

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