PMID: 3039133Aug 1, 1987

Tricyclic compounds as selective antimuscarinics. 1. Structural requirements for selectivity toward the muscarinic acetylcholine receptor in a series of pirenzepine and imipramine analogues

Journal of Medicinal Chemistry
W G EberleinN Mayer

Abstract

The M1-selective antiulcer drug pirenzepine (1) is a tricyclic compound with close resemblance to tricyclic psychotropic agents such as imipramine (2). Despite this fact, pirenzepine is devoid of any psychotropic effects, exhibiting measurable antagonistic effects in biochemical assays and receptor binding studies only toward the muscarinic receptor system. To understand how different groups in these tricyclic molecules affect binding affinities, a set of nine compounds structurally related to pirenzepine (1) and imipramine (2) has been selected for analysis, comprising three different tricycles and three different side chains. The compounds were tested for their affinity to the imipramine and muscarinic receptors in homogenized rat cortex tissue. The result of these studies suggests that it is the nature and placement of accessory groups that determine the differences in receptor recognition and the binding process. In the case of pirenzepine (1), preferential binding toward the muscarinic receptor is brought about by the endocyclic amide group, by the positioning of the protonated N atom of the side chain, and to a minor extent by the exocyclic amide group. From these findings a putative model for the explanation of selective...Continue Reading

Citations

Jul 1, 1990·Medicinal Research Reviews·C Melchiorre
Feb 12, 2008·Journal of Combinatorial Chemistry·Fuqiang ShiXu Bai
Jul 1, 1991·Journal of Medicinal Chemistry·Y KartonK A Jacobson
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Fuqiang ShiYa-Feng Li
Mar 24, 2016·The Journal of Organic Chemistry·Keith RamigEdyta M Greer

Related Concepts

Imipramine receptor
Carrier Proteins
Insula of Reil
Tofranil
Pirenzepin von ct
Receptors, Drug
Muscarinic Acetylcholine Receptor
Structure-Activity Relationship
Synaptic Receptors

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