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
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Yoneyama, Kihei; Venkatesh, Bharath A; Wu, Colin O et al. (2018) Diabetes mellitus and insulin resistance associate with left ventricular shape and torsion by cardiovascular magnetic resonance imaging in asymptomatic individuals from the multi-ethnic study of atherosclerosis. J Cardiovasc Magn Reson 20:53
Uddin, S M Iftekhar; Mirbolouk, Mohammadhassan; Dardari, Zeina et al. (2018) Erectile Dysfunction as an Independent Predictor of Future Cardiovascular Events. Circulation 138:540-542
Savji, Nazir; Meijers, Wouter C; Bartz, Traci M et al. (2018) The Association of Obesity and Cardiometabolic Traits With Incident HFpEF and HFrEF. JACC Heart Fail 6:701-709
Vella, Chantal A; Allison, Matthew A (2018) Associations of abdominal intermuscular adipose tissue and inflammation: The Multi-Ethnic Study of Atherosclerosis. Obes Res Clin Pract 12:534-540
Thomas, Isac C; Thompson, Caroline A; Yang, Mingan et al. (2018) Thoracic Aorta Calcification and Noncardiovascular Disease-Related Mortality. Arterioscler Thromb Vasc Biol 38:1926-1932
Balakrishnan, Poojitha; Jones, Miranda R; Vaidya, Dhananjay et al. (2018) Ethnic, Geographic, and Genetic Differences in Arsenic Metabolism at Low Arsenic Exposure: A Preliminary Analysis in the Multi-Ethnic Study of Atherosclerosis (MESA). Int J Environ Res Public Health 15:
Osibogun, Olatokunbo; Ogunmoroti, Oluseye; Spatz, Erica S et al. (2018) Is self-rated health associated with ideal cardiovascular health? The Multi-Ethnic Study of Atherosclerosis. Clin Cardiol 41:1154-1163
Ying, Wendy; Zhao, Di; Ouyang, Pamela et al. (2018) Sex Hormones and Change in N-Terminal Pro-B-Type Natriuretic Peptide Levels: The Multi-Ethnic Study of Atherosclerosis. J Clin Endocrinol Metab 103:4304-4314
Kwon, Younghoon; Jacobs Jr, David R; Lutsey, Pamela L et al. (2018) ""Sleep disordered breathing and ECG R-wave to radial artery pulse delay, The Multi-Ethnic Study of Atherosclerosis"". Sleep Med 48:172-179

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