title: Novel, potent, and selective quinoxaline-based 5-HT(3) receptor ligands. 1. Further structure-activity relationships and pharmacological characterization.
abstract: We investigated the pharmacological profile of a novel series of quinoxaline-based 5-HT(3) receptor ligands bearing an extra basic moiety on the piperazine N-4. High affinity and selectivity were dependent on the electronic properties of the substituents, and at cardiac level 3a and 3c modulated chronotropy but not inotropy. In von Bezold-Jarisch reflex test 3a-c were partial agonists while 3i was a full agonist. Preliminary pharmacokinetic studies indicated that 3a is a brain penetrating agent.
authors.affiliation: European Research Centre for Drug Discovery and Development, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.forename: Roberta
authors.initials: R
authors.lastname: Budriesi
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.forename: Elena
authors.initials: E
authors.lastname: Morelli
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borrelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Isabella
authors.initials: I
authors.lastname: Fiorini
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Ioan
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarini
authors.forename: Alfredo
authors.initials: A
authors.lastname: Cagnotto
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Claudia
authors.initials: C
authors.lastname: Fracasso
authors.forename: Silvio
authors.initials: S
authors.lastname: Caccia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D054333:Drug Partial Agonism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008024:Ligands; D009200:Myocardial Contraction / Q000187:drug effects; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012018:Reflex / Q000187:drug effects; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011758:Pyrroles; D011810:Quinoxalines; D058827:Serotonin 5-HT3 Receptor Agonists; D058831:Serotonin 5-HT3 Receptor Antagonists