4'- And 4',4"-Substituted-3alpha(diphenylmethoxy)tropane Analogs As Cocaine Therapeutics
Description of Invention:
The invention provides a series of 4'- and 4',4"-substituted benztropine analogs that demonstrate high affinity binding (K1<30 nM) to the dopamine transporter and bind selectively (>100-fold) over the other monoamine transporters. These compounds block dopamine reuptake in vitro and yet do not demonstrate a cocaine-like behavioral profile in animal models of psychomotor stimulant abuse. Structure-Activity Relationships suggest that these compounds interact at a binding domain that differs from that of cocaine at the dopamine transporter. These compounds represent an unprecedented class of dopamine uptake inhibitors that may have potential as cocaine-abuse therapeutics, since they have neurochemical similarities to cocaine and yet do not appear to have abuse liability. Further, radiolabeled analogs will be suitable for imaging the dopamine transporter in mammalian brain using SPECT and PET and thus would be useful in the diagnoses and monitoring of neurodegenerative disorders involving the dopaminergic system (e.g., Parkinson's disease). In addition, the invention provides pharmaceutical compositions comprising an analog of the invention and a pharmaceutically acceptable carrier excipient.
Inventors:
AH Newman (NIDA) AC Allen (NIDA) RH Kline (NIDA) S Izenwasser (NIDA) JL Katz (NIDA)
Patent Status:
DHHS Reference No. E-078-1995/1 --
U.S. Patent 5,792,775 issued 11 Aug 1998
Portfolios: Central Nervous System
Central Nervous System -Therapeutics-Neurological Therapeutics-Antiparkinsonian Central Nervous System -Therapeutics-Psychotherapeutics-Drug Dependence Central Nervous System -Therapeutics Central Nervous System -Diagnostics
For Additional Information Please Contact: Norbert J. Pontzer PhD JD
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301) 435-5502
Email: pontzern@mail.nih.gov
Fax: (301) 402-0220
