title: Rigid analogs of DMPP as probes for the nicotinic receptors.
abstract: Chemical manipulation of the nicotinic agonist DMPP, endowed with modest activity on the central receptors, definitely improved its affinity and pharmacokinetic properties. Although their pharmacophore is somehow different from that of classical nicotinic ligands, some DMPP derivatives show low nanomolar affinity for the central nicotinic receptors. Introduction of rigidity in the structure of DMPP and in that of its analogue 1-(3-pyridyl)piperazine, resulted in molecules with lower or null affinity for the central nicotinic receptors. This suggests that the frozen structures chosen either do not represent the bioactive conformation, or their volume is not compatible with the space available within the interaction site.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Guandalini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Martini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martelli
authors.forename: M Novella
authors.initials: MN
authors.lastname: Romanelli
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
mesh_terms: D000818:Animals; D001665:Binding Sites; D004246:Dimethylphenylpiperazinium Iodide / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D004246:Dimethylphenylpiperazinium Iodide