title: Structure-activity relationships and pharmacological profile of selective tricyclic antimuscarinics.
abstract: The discovery of the M1-selective receptor antagonist pirenzepine was the impetus for a research project directed towards the development of selective muscarinic antagonists. In the pursuit of this objective, compounds with different selectivity profiles have been found. AF-DX 116 was the first cardioselective antagonist synthesized. Subsequently novel M2 receptor antagonists have been discovered with higher potency and selectivity. Moreover, a pirenzepine-type compound UH-AH 37 has been identified that, in contrast to pirenzepine, shows a higher affinity for ileal than for atrial muscarinic receptors. Among tricyclic muscarinic receptor antagonists three different selectivity profiles have been identified, namely: M1 greater than M3 greater than M2, Msm for pirenzepine; M2 greater than M1 greater than M3, Msm for AF-DX 116, AF-DX 384, AQ-RA 741; and Msm congruent to M1 greater than M2, M3 for UH-AH 37 and its (+) enantiomer.
authors.forename: W G
authors.initials: WG
authors.lastname: Eberlein
authors.forename: W
authors.initials: W
authors.lastname: Engel
authors.forename: G
authors.initials: G
authors.lastname: Mihm
authors.forename: K
authors.initials: K
authors.lastname: Rudolf
authors.forename: B
authors.initials: B
authors.lastname: Wetzel
authors.forename: M
authors.initials: M
authors.lastname: Entzeroth
authors.forename: N
authors.initials: N
authors.lastname: Mayer
authors.forename: H N
authors.initials: HN
authors.lastname: Doods
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D006801:Humans; D010276:Parasympatholytics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000929:Antidepressive Agents, Tricyclic; D010276:Parasympatholytics