The effect of 6-substituted-4',4"-difluorobenztropines on monoamine transporters and the muscarinic M1 receptor.
A series of racemic 6-hydroxy and carboalkoxy substituted-4('),4"-difluorobenztropines was synthesized and evaluated for binding at the dopamine (DAT), the serotonin (SERT), the norepinephrine (NET) transporters, and the muscarinic M1 receptor. Each of the analogues displaced [(3)H]WIN 35,428 (DAT) with a range of affinities from 5.81 to 175 nM and [(3)H]pirenzepine (M1), with a range of affinities ( K(i)= -8430 nM). Binding affinities at the SERT and the NET were generally low.
Grundt
Peter
P
Medicinal Chemistry, National Institute on Drug Abuse--Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224, USA. pgrundt@intra.nida.nih.gov
Kopajtic
Theresa A
TA
Katz
Jonathan L
JL
Newman
Amy Hauck
AH
D001590:Benztropine / Q000737:chemistry* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011485:Protein Binding / Q000502:physiology; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D043643:Receptor, Muscarinic M1; D050486:Serotonin Plasma Membrane Transport Proteins; D027981:Symporters; D001590:Benztropine