Methadone is an important long-term maintenance therapy for drug addiction and currently is frequently used for analgesia. However, methadone prolongs the QT interval on the electrocardiogram and this increases risk for life threatening arrhythmias and has led to the FDA's placing a """"""""black box"""""""" warning on methadone's label. Initial studies in our laboratory have shown that one of the stereoisomers of methadone causes significantly less QT prolongation and this isomer possesses the analgesic effect of methadone. The studies outlined in the grant propose to confirm the safety of the R isomer in a model to access proarrhythmia that the FDA proposes for the animal evaluation of arrhythmic risk and then to determine if the isomer causes less QT prolongation in the dog at therapeutic and higher than routine therapeutic doses of R methadone as compared to racemic methadone. These are necessary steps for the submission of a new drug application and the eventual commercial availability of the methadone isomer as a safer treatment for analgesia and addiction.

Public Health Relevance

Methadone is frequently used for pain treatment and drug addiction, but the current formulation poses a serious risk of arrhythmias. The R isomer of methadone does not cause the same electrophysiologic changes (QT prolongation) and thus would not pose the same risk for arrhythmias. Studies in this grant set out to show that the R isomer is a safer methadone and would pose less of a risk for life threatening arrhythmias to patient.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43HL095160-01A1
Application #
7798956
Study Section
Special Emphasis Panel (ZRG1-CVRS-B (10))
Program Officer
Lathrop, David A
Project Start
2010-04-15
Project End
2010-10-31
Budget Start
2010-04-15
Budget End
2010-10-31
Support Year
1
Fiscal Year
2010
Total Cost
$102,910
Indirect Cost
Name
Academic Pharmaceuticals, Inc.
Department
Type
DUNS #
874285984
City
Lake Bluff
State
IL
Country
United States
Zip Code
60044
Subramanya, Vinita; Zhao, Di; Ouyang, Pamela et al. (2018) Sex hormone levels and change in left ventricular structure among men and post-menopausal women: The Multi-Ethnic Study of Atherosclerosis (MESA). Maturitas 108:37-44
Emdin, Connor A; Khera, Amit V; Chaffin, Mark et al. (2018) Analysis of predicted loss-of-function variants in UK Biobank identifies variants protective for disease. Nat Commun 9:1613
Aaron, Carrie P; Schwartz, Joseph E; Hoffman, Eric A et al. (2018) A Longitudinal Cohort Study of Aspirin Use and Progression of Emphysema-like Lung Characteristics on CT Imaging: The MESA Lung Study. Chest 154:41-50
Ong, Kwok Leung; Morris, Margaret J; McClelland, Robyn L et al. (2018) Relationship of Lipids and Lipid-Lowering Medications With Cognitive Function: The Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 187:767-776
Oelsner, Elizabeth C; Smith, Benjamin M; Hoffman, Eric A et al. (2018) Associations between emphysema-like lung on CT and incident airflow limitation: a general population-based cohort study. Thorax 73:486-488
Moazzami, Kasra; Ostovaneh, Mohammad Reza; Ambale Venkatesh, Bharath et al. (2018) Left Ventricular Hypertrophy and Remodeling and Risk of Cognitive Impairment and Dementia: MESA (Multi-Ethnic Study of Atherosclerosis). Hypertension 71:429-436
Wang, Jian; Shete, Sanjay (2018) Estimation of indirect effect when the mediator is a censored variable. Stat Methods Med Res 27:3010-3025
Oelsner, Elizabeth C; Smith, Benjamin M; Hoffman, Eric A et al. (2018) Prognostic Significance of Large Airway Dimensions on Computed Tomography in the General Population. The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study. Ann Am Thorac Soc 15:718-727
Jones, Miranda R; Tellez-Plaza, Maria; Vaidya, Dhananjay et al. (2018) Ethnic, geographic and dietary differences in arsenic exposure in the multi-ethnic study of atherosclerosis (MESA). J Expo Sci Environ Epidemiol :
Keaton, Jacob M; Gao, Chuan; Guan, Meijian et al. (2018) Genome-wide interaction with the insulin secretion locus MTNR1B reveals CMIP as a novel type 2 diabetes susceptibility gene in African Americans. Genet Epidemiol 42:559-570

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