Novel 5-HT treatments for METH post-addiction therapy

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44DA016496-02A1
Agency Tracking Number: DA016496
Amount: $783,774.00
Phase: Phase II
Program: SBIR
Awards Year: 2005
Solicitation Year: 2005
Solicitation Topic Code: N/A
Solicitation Number: PHS2005-2
Small Business Information
1420 5Th Ave, Suite 2600, Seattle, WA, 98101
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 CLARK TEDFORD
 (216) 591-0034
 CTEDFORD@OMEROS.COM
Business Contact
Phone: (206) 623-4688
Research Institution
N/A
Abstract
DESCRIPTION (provided by applicant): The overall objective of this research is to identify putative drug treatments in the pre-clinical setting that can rapidly translate into post-withdrawal pharmacotherapy for methamphetamine (METH) addiction. Methamphetamine is an increasingly popular psychostimulant/hallucinogenic drug with an extremely high abuse liability. Presently, there is no cure for METH addiction. Indeed, the overwhelming majority (up to 85 percent) of patients undergoing modern-day drug rehabilitation relapse back into compulsive drug taking. Phase I studies have revealed that post-withdrawal administration of the 5-HT antagonist mianserin and mirtazapine, but not ketanserin reversed the sensitized behaviors established by METH, The establishment of the behavioral and biochemical paradigms at Solentix was successfully completed in 6 months and baseline as well as compound profiles have been generated for the agents mianserin, mirtazapine and ketanserin. The present SBIR grant phase II is posed to extend these basic questions to the clinical/commercial arena, with the objective of developing novel or identified 5-HT antagonists as potential treatments of METH addiction. A companion R01 grant has been awarded and initiated by Dr. Napier and will allow extensive basic research questions to be addressed on the involvement of 5-HT mechanisms and METH addiction, while the current SBIR grant will target commercialization activities of identified drug treatments. In addition, we have identified novel chemical structures that would be synthesized with the focused goal of developing the best pharmacological profile for reversal of METH-induced sensitization behavioral and biochemical events. The unique strengths of this grant are the focus on the drug-induced neuroadaptive changes in the brain, which will allow agents to be selected for METH drug addiction. The following aims are proposed: Five Specific Aims are proposed for the present SBIR Phase II. Specific Aims include: 1) Rodent behavioral METH-sensitization testing; 2) Novel chemistry synthesis; A patent has been filed to provide for the development of a large library of novel 5-HT compounds with specific substitutions that would provide unique receptor selectivity profiles. 3) In vitro drug screening and profiling; 4) Ex vivo CNS penetration testing; and 5) Drug Candidate - Biochemical & Electrophysiological Testing. The overall phase II SBIR goals will be to establish additional or novel drug candidates for METH addiction therapy through internal Omeros drug discovery efforts. The results of this research may also be utilized to explore additional therapeutic treatments for other drugs of abuse and subsequent identification of novel therapies.

* Information listed above is at the time of submission. *

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