title: Pre- and postsynaptic dopaminergic activities of indolizidine and quinolizidine derivatives of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP). Further developments of a dopamine receptor model.
abstract: Pre- and postsynaptic dopaminergic activities of a series of indolizidine and quinolizidine analogues of 3-(3-hydroxyphenyl)-N-(n-propyl)piperidine (3-PPP) have been studied. The pharmacological data have been interpreted in terms of a previously reported model for interactions with dopamine pre- and postsynaptic D2-receptors and molecular mechanics (MM2(85] calculated geometries and conformational energies. The model has been further developed with respect to the receptor topography in the vicinity of the nitrogen binding site. In particular, a novel spatial orientation of the important "propyl cleft" has been proposed. This cleft is suggested to be located mainly above a plane through the receptor-bound substrate. The biologically active agonist and antagonist conformations of the enantiomers of 3-PPP have been reinvestigated.
authors.affiliation: Organic Chemistry 3, Chemical Center, University of Lund, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Liljefors
authors.forename: K P
authors.initials: KP
authors.lastname: Bøgesø
authors.forename: J
authors.initials: J
authors.lastname: Hyttel
authors.forename: H
authors.initials: H
authors.lastname: Wikström
authors.forename: K
authors.initials: K
authors.lastname: Svensson
authors.forename: A
authors.initials: A
authors.lastname: Carlsson
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D006916:5-Hydroxytryptophan / Q000378:metabolism; D000818:Animals; D015259:Dopamine Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D018492:Dopamine Antagonists; D008297:Male; D008961:Models, Structural; D008968:Molecular Conformation; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D015259:Dopamine Agents; D018492:Dopamine Antagonists; D010880:Piperidines; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; C026539:preclamol; D006916:5-Hydroxytryptophan