The effect of 6-substituted-4',4"-difluorobenztropines on monoamine transporters and the muscarinic M1 receptor

Peter Grundt; Theresa A Kopajtic; Jonathan L Katz; Amy Hauck Newman

doi:10.1016/j.bmcl.2004.03.075

The effect of 6-substituted-4',4"-difluorobenztropines on monoamine transporters and the muscarinic M1 receptor

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3295-8. doi: 10.1016/j.bmcl.2004.03.075.

Authors

Peter Grundt¹, Theresa A Kopajtic, Jonathan L Katz, Amy Hauck Newman

Affiliation

¹ 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

PMID: 15149693
DOI: 10.1016/j.bmcl.2004.03.075

Abstract

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.

Publication types

Research Support, U.S. Gov't, P.H.S.

MeSH terms

Benztropine / chemistry*
Benztropine / metabolism
Dopamine Plasma Membrane Transport Proteins
Membrane Glycoproteins / metabolism*
Membrane Transport Proteins / metabolism*
Nerve Tissue Proteins / metabolism*
Norepinephrine Plasma Membrane Transport Proteins
Protein Binding / physiology
Receptor, Muscarinic M1 / metabolism*
Serotonin Plasma Membrane Transport Proteins
Symporters / metabolism*

Substances

Dopamine Plasma Membrane Transport Proteins
Membrane Glycoproteins
Membrane Transport Proteins
Nerve Tissue Proteins
Norepinephrine Plasma Membrane Transport Proteins
Receptor, Muscarinic M1
Serotonin Plasma Membrane Transport Proteins
Symporters
Benztropine