This application is in response to SPIRCAP RFA DA 00-001. The application brings together a group of experienced investigators from six separate organization who have an interest in developing medications for the treatment of cocaine addiction. Dr. F. Ivy Carroll from the Research Triangle Institute, Dr. Barbara S. Fox from Addiction Therapies, Dr. James L. Howard from Howard Associates, Dr. Leonard L. Howell from Emory University, Drs. Charles R. Schuster and Chris Ellyn Johanson from Wayne State University, and Drs. Thomas R. and Theresa A. Korsten from Yale University. These investigators have extensive experience in organic and medicinal chemistry, animal behavioral pharmacology, and clinical evaluation. Even though considerable effort has been devoted toward solving the cocaine addiction problem, no suitable pharmacotherapy is presently available. As part of other programs supported by NIDA, we have discovered novel 3-phenyltropane analogs which possess properties that provide promise that one of these compounds will be useful as a medication for treating cocaine addicts without deleterious side effects. Novel 3-phenyltropane analogs that show high affinity have been discovered and developed. Animal behavioral studies have shown that some of these compounds possess pharmacological properties desirable for a treatment medication. In order to take advantage of this significant development, the present application puts forth a proposal to first conduct preclinical and then clinical studies in humans to determine the potential of the DAT selective 3- phenyltropane analogs as medications for treatment of cocaine addicts. The hypotheses to be tested are: (1) a 3-phenyltropane analog highly selective for the DAT will be safe to use in humans; (2) a DAT-selective 3-phenyltropane will be useful for treating humans addicted to cocaine; and (3) serotonin-selective reuptake inhibitors such as fluoxetine, paroxetine, and sertraline will modulate the behavioral effects induced by the DAT-selective 3-phenyltropane.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19DA013326-04
Application #
6634305
Study Section
Special Emphasis Panel (ZDA1-KXA-N (18))
Program Officer
Chiang, Nora
Project Start
2000-09-30
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2010-05-31
Support Year
4
Fiscal Year
2007
Total Cost
$650,551
Indirect Cost
Name
Research Triangle Institute
Department
Type
DUNS #
004868105
City
Research Triangle
State
NC
Country
United States
Zip Code
27709
Carroll, F Ivy; Kosten, Thomas R; Buda, Jeffrey J et al. (2018) A Double-Blind, Placebo-Controlled Trial Demonstrating the Safety, Tolerability, and Pharmacokinetics of Single, Escalating Oral Doses of RTI-336. Front Pharmacol 9:712
Kimmel, Heather L; Nye, Jonathon A; Voll, Ronald et al. (2012) Simultaneous measurement of extracellular dopamine and dopamine transporter occupancy by cocaine analogs in squirrel monkeys. Synapse 66:501-8
Howell, Leonard L; Murnane, Kevin S (2008) Nonhuman primate neuroimaging and the neurobiology of psychostimulant addiction. Ann N Y Acad Sci 1141:176-94
Howell, Leonard L (2008) Nonhuman primate neuroimaging and cocaine medication development. Exp Clin Psychopharmacol 16:446-57
Kimmel, Heather L; Negus, S Stevens; Wilcox, Kristin M et al. (2008) Relationship between rate of drug uptake in brain and behavioral pharmacology of monoamine transporter inhibitors in rhesus monkeys. Pharmacol Biochem Behav 90:453-62
Howell, Leonard L; Carroll, F Ivy; Votaw, John R et al. (2007) Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys. J Pharmacol Exp Ther 320:757-65
Kimmel, Heather L; O'Connor, Joann A; Carroll, F Ivy et al. (2007) Faster onset and dopamine transporter selectivity predict stimulant and reinforcing effects of cocaine analogs in squirrel monkeys. Pharmacol Biochem Behav 86:45-54
Carroll, F Ivy; Fox, Barbara S; Kuhar, Michael J et al. (2006) Effects of dopamine transporter selective 3-phenyltropane analogs on locomotor activity, drug discrimination, and cocaine self-administration after oral administration. Eur J Pharmacol 553:149-56