title: Exploring multitarget interactions to reduce opiate withdrawal syndrome and psychiatric comorbidity.
abstract: Opioid addiction is often characterized as a chronic relapsing condition due to the severe somatic and behavioral signs, associated with depressive disorders, triggered by opiate withdrawal. Since prolonged abstinence remains a major challenge, our interest has been addressed to such objective. Exploring multitarget interactions, the present investigation suggests that 3 or its (S)-enantiomer and 4, endowed with effective α2C-AR agonism/α2A-AR antagonism/5-HT1A-R agonism, or 7 and 9-11 producing efficacious α2C-AR agonism/α2A-AR antagonism/I2-IBS interaction might represent novel multifunctional tools potentially useful for reducing withdrawal syndrome and associated depression. Such agents, lacking in sedative side effects due to their α2A-AR antagonism, might afford an improvement over current therapies with clonidine-like drugs.
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Del Bello
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Diamanti
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Mammoli
authors.affiliation: School of Pharmacy, Pharmacognosy Unit, University of Camerino , Via Madonna delle Carceri 9, 62032 Camerino, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mattioli
authors.affiliation: School of Pharmacy, Pharmacognosy Unit, University of Camerino , Via Madonna delle Carceri 9, 62032 Camerino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Titomanlio
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Piergentili
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Wilma
authors.initials: W
authors.lastname: Quaglia
authors.affiliation: Pharmacology & Toxicology Department, Rottapharm-Madaus , 20052 Monza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lanza
authors.affiliation: Pharmacology & Toxicology Department, Rottapharm-Madaus , 20052 Monza, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabatini
authors.affiliation: Pharmacology & Toxicology Department, Rottapharm-Madaus , 20052 Monza, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Caselli
authors.affiliation: Recordati S.pA., Drug Discovery , Via Civitali 1, 20148 Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Poggesi
authors.affiliation: School of Pharmacy, Medicinal Chemistry Unit, University of Camerino , Via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
keywords: 5-HT1A agonists; I2−IBS ligands; antidepressant-like effect; morphine withdrawal symptoms reduction; α2-Adrenergic ligands