Sustained-Release Derivatives of Hydroxylated Analogs of Substituted 1-
[2[bis(aryl)methoxy]-ethyl] -Piperazines and -Homopiperazines and Their
Use as Noncompetitive Antagonists of Dopamine Reuptake Inhibitors
Description of Invention:
Cocaine abuse and addiction is a major public health problem in the United States and several other countries. The biomedical and psychosocial cost of cocaine abuse and addiction is considerable, and to date, there is no effective treatment for addiction. In an effort to develop an efficacious treatment for cocaine addiction, this invention describes sustained-release derivatives of hydroxylated analogs of substituted 1-[2bis(aryl)methoxy]ethyl]-piperazines and -homopiperazines. These compounds bind to the dopamine transporter but do not inhibit dopamine reuptake, thereby providing a sustained increase in the level of extracellular dopamine and providing the drug abuser with some relief from drug craving due to dopamine deficiency, yet they simultaneously inhibit cocaine from further elevating the level of extracellular dopamine and increasing the probability of additional toxic side effects.
These derivatives have been shown to produce moderate to long-acting attenuation
of cocaine-induced activation of mesolimbic dopamine neurons in rhesus monkeys,
resulting in decreased cocaine self-administration without concurrent effects on
food response. The present invention provides these sustained-release derivatives, pharmaceutical compositions comprising the same, and a method of using such sustained release derivatives as a treatment for cocaine addiction.
Inventors:
RB Rothman (NIDA) KC Rice (NIDDK) DB Lewis (NIDDK) D Matecka (NIDDK)
JR Glowa (NIDDK)
Patent Status:
DHHS Reference No. E-152-1996/0 --
U.S. Patent 6,387,389 issued 14 May 2002
Portfolios: Central Nervous System
Central Nervous System -Therapeutics-Psychotherapeutics-Drug Dependence Central Nervous System -Therapeutics
For Additional Information Please Contact: Charlene A. Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-4689
Email: sydnorc@mail.nih.gov
Fax: 301/402-0220
