1043533-91-0Relevant articles and documents
Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms
Ubaldi, Massimo,Del Bello, Fabio,Domi, Esi,Pigini, Maria,Nasuti, Cinzia
, p. 122 - 128 (2015)
We have recently demonstrated that allyphenyline, behaving as α2C-adrenoceptor/serotonin 5-HT1A receptor agonist and α2A-adrenoceptor antagonist, in mice enhanced morphine analgesia, attenuated morphine withdrawal symptoms, showed significant antidepressant-like activity and was devoid of sedative side effects. Opioid and alcohol withdrawal shares several common neurobiological and molecular mechanisms. Therefore, in this study we expanded our analysis of the pharmacological properties of allyphenyline by investigating its ability to prevent the expression of somatic withdrawal signs, anxiety-like behavior and hyperlocomotion associated with chronic ethanol intoxication. Rats were subjected to induction of ethanol dependence via repeated daily intragastric ethanol (20%) administration for 4 consecutive days. Twelve hours after the last alcohol administration, somatic alcohol withdrawal signs were scored. Results revealed a significant expression of physical withdrawal signs that were not affected by intraperitoneal (i.p.) administration of allyphenyline at the doses of 0.05, 0.275 and 0.5 mg/kg. In contrast, allyphenyline (0.05 and 0.275 mg/kg i.p.) significantly reduced hyperanxiety-like behavior observed 6 days after alcohol intoxication as measured using the defensive burying test. Allyphenyline also reduced open field hyperlocomotor activity associated with alcohol withdrawal. Notably, the anxiolytic effect of the compound, as well as the already reported antidepressant action, was observed at very low doses, suggesting the involvement of its α2C-adrenoceptor/serotonin 5-HT1A receptor agonism. Therefore, the present investigation suggests that allyphenyline might represent an interesting pharmacological tool to investigate the potential of compounds exhibiting α2C-adrenoceptor/serotonin 5-HT1A receptor agonism and α2A-adrenoceptor antagonism in the treatment of hyperanxiety and hyperlocomotion occurring during alcohol withdrawal in dependent subjects.
Biological profile and bioavailability of imidazoline compounds on morphine tolerance modulation
Caprioli, Giovanni,Mammoli, Valerio,Ricciutelli, Massimo,Sagratini, Gianni,Ubaldi, Massimo,Domi, Esi,Mennuni, Laura,Sabatini, Chiara,Galimberti, Chiara,Ferrari, Flora,Milia, Chiara,Comi, Eleonora,Lanza, Marco,Giannella, Mario,Pigini, Maria,Del Bello, Fabio
, p. 219 - 224 (2015)
Tolerance to opioid administration represents a serious medical alert in different chronic conditions. This study compares the effects of the imidazoline compounds 1, 2, and 3 on morphine tolerance in an animal model of inflammatory pain in the rat. 1, 2,
α2-adrenoreceptors profile modulation. 4. From antagonist to agonist behavior
Gentili, Francesco,Cardinaletti, Claudia,Vesprini, Cristian,Carrieri, Antonio,Ghelfi, Francesca,Farande, Aniket,Giannella, Mario,Piergentili, Alessandro,Quaglia, Wilma,Laurila, Jonne M.,Huhtinen, Anna,Scheinin, Mika,Pigini, Maria
experimental part, p. 4289 - 4299 (2009/05/07)
The goal of the present study was to modulate the receptor interaction properties of known α2-adrenoreceptor (AR) antagonists to obtain novel α2-AR agonists with desirable subtype selectivity. Therefore, a phenyl group or one of its bioisosteres or aliphatic moieties with similar steric hindrance were introduced into the aromatic ring of the antagonist lead basic structure. The functional properties of the novel compounds allowed our previous observations to be confirmed. The high efficacy of 7, 12, and 13 as α2-AR agonists and the significant α2C-AR subtype selective activation displayed by 11 and 15 demonstrated that favorable interactions to induce α2-AR activation were formed between the pendant groups of the ligands and the aromatic cluster present in transmembrane domain 6 of the binding site cavity of the receptors.
