Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms

Ubaldi, Massimo; Bello, Fabio Del; Domi, Esi; Pigini, Maria; Nasuti, Cinzia

doi:10.1016/j.ejphar.2015.04.005

Cited by 7 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments performed in the presence of the α 2 ‐AR antagonist yohimbine and the serotonin 5‐HT 1A receptor (5‐HT 1A ‐R) antagonist WAY100135 suggested that not only α 2C ‐AR but also 5‐HT 1A ‐R activation was involved in the observed antidepressant‐like activity . In addition, 1 reduced hyperanxiety‐like behavior after alcohol intoxication at the same low dose . On the other hand, such psychiatric effects agreed with the 5‐HT 1A ‐mediated functions.…”

Section: Introductionmentioning

confidence: 73%

“…[5,11] In addition, 1 reduced hyperanxiety-like behavior after alcoholi ntoxication at the same low dose. [12] On the other hand, such psychiatric effectsa greed with the 5-HT 1A -mediatedf unctions. Therefore, fort he first time, our studies indicated that ligands bearing the 2-substituted imidazoline nucleus as as tructural motif werealso suitable to interactwith 5-HT 1A -R.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

et al. 2016

Self Cite

View full text Add to dashboard Cite

The involvement of the serotonin 5‐HT1A receptor (5‐HT1A‐R) in the antidepressant effect of allyphenyline and its analogues indicates that ligands bearing the 2‐substituted imidazoline nucleus as a structural motif interact with 5‐HT1A‐R. Therefore, we examined the 5‐HT1A‐R profile of several imidazoline molecules endowed with a common scaffold consisting of an aromatic moiety linked to the 2‐position of an imidazoline nucleus by a biatomic bridge. Our aim was to discover other ligands targeting 5‐HT1A‐R and to identify the structural features favoring 5‐HT1A‐R interaction. Structure–activity relationships, supported by modeling studies, suggested that some structural cliché such as a polar function and a methyl group in the bridge, as well as proper steric hindrance in the aromatic area of the above scaffold, favored 5‐HT1A‐R recognition and activation. We also highlighted the potent antidepressant‐like effect (mouse forced swimming test) of (S)‐(+)‐19 [(S)‐(+)‐naphtyline] at very low dose (0.01 mg kg−1). This effect was clearly mediated by 5‐HT1A, as it was significantly reduced by pretreatment with the 5‐HT1A antagonist WAY100635.

show abstract

Section: Introductionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Considering the potent gastroprotective, fundic relaxing and anxiolytic [26] properties of allyphenyline we propose that this compound may be a useful tool in the therapy of both peptic ulcers and non-ulcer dyspepsia.…”

Section: It Is Well-established That Peptic Ulcers Develop As a Resumentioning

confidence: 99%

“…Regarding other receptors, allyphenyline also binds to and activate 5HT1A receptors [25], and dual activation of α2C-ARs and 5HT1A receptors by this compound elicited antidepressant-and anxiolytic-like effects in rodents [25,26]. 5HT1A receptors have been implicated in numerous GI processes, such as gastric mucosal protection [27,28], inhibition of cholinergic gastric contractions [29,30], as well as modulation of colonic motility [31].…”

Section: Introductionmentioning

confidence: 99%

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

et al. 2016

Self Cite

View full text Add to dashboard Cite

Background. Allyphenyline, a novel α2-adrenoceptor (AR) ligand has been shown to selectively activate α2C-adrenoceptors (AR) and 5HT1A receptors, but also to behave as a neutral antagonist of α2A-ARs. We exploited this unique pharmacological profile to analyze the role of α2C-ARs and 5HT1A receptors in the regulation of gastric mucosal integrity and gastrointestinal motility. Methods. Similar inhibition was observed in the colon, however, in this case only ARC 239 reduced this effect, while neither selective inhibition of α2C-ARs and 5HT1A receptors, nor genetic deletion of α2A-and α2B-ARs influenced it. Conclusions. Activation of both central α2C-ARs and 5HT1A receptors contributes to the gastroprotective action of allyphenyline in rats. Its inhibitory effect on fundic contractions is mediated by 5HT1A receptors, but neither α2-ARs, nor 5HT1A receptors take part in its inhibitory effect on colonic contractility in mice.

show abstract

“…17−19 At low dose 1 also reduced hyperanxiety-like behavior after alcohol intoxication. 20 In contrast, the −CHCH− bridge induced efficacious I 1 -and I 2 -IBS recognition, as demonstrated by tracizoline (3) (pK i : I 1 -IBS 7.72, I 2 -IBS 8.72, α 2 -ARs < 6), 21 whereas the −NH− CH 2 − chain might be tolerated by ligands addressed to I 1 -, I 2 -IBS and α 2 -ARs, as reported for 4 (pK i : I 1 -IBS 9.30, I 2 -IBS 7.48, α 2 -ARs 7.14). 22,23 Our studies also indicated that the introduction of suitable decorations in the ortho position of the phenyl ring conferred to the ligand an interesting profile modulation from antagonism to agonism.…”

mentioning

confidence: 99%

Combined Interactions with I₁-, I₂-Imidazoline Binding Sites and α₂-Adrenoceptors To Manage Opioid Addiction

Giusepponi

Cifani

Bonaventura

et al. 2016

ACS Med. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Tolerance and dependence associated with chronic opioid exposure result from molecular, cellular, and neural network adaptations. Such adaptations concern opioid and nonopioid systems, including α 2 -adrenoceptors (α 2 -ARs) and I 1 -and I 2 -imidazoline binding sites (IBS). Agmatine, one of the hypothesized endogenous ligands of IBS, targeting several systems including α 2 -ARs and IBS, proved to be able to regulate opioid-induced analgesia and to attenuate the development of tolerance and dependence. Interested in the complex pharmacological profile of agmatine and considering the nature of its targets, we evaluated two series of imidazolines, rationally designed to simultaneously interact with I 1 -/I 2 -IBS or I 1 -/I 2 -IBS/α 2 -ARs. The compounds showing the highest affinities for I 1 -/I 2 -IBS or I 1 -/I 2 -IBS/α 2 -ARs have been selected for their in vivo evaluation on opiate withdrawal syndrome. Interestingly, 9, displaying I 1 -/I 2 -IBS/α 2 -ARs interaction profile, appears more effective in reducing expression and acquisition of morphine dependence and, therefore, might be considered a promising tool in managing opioid addiction.

show abstract

Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms

Cited by 7 publications

References 55 publications

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

Combined Interactions with I₁-, I₂-Imidazoline Binding Sites and α₂-Adrenoceptors To Manage Opioid Addiction

Contact Info

Product

Resources

About

Investigation of allyphenyline efficacy in the treatment of alcohol withdrawal symptoms

Cited by 7 publications

References 55 publications

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT1A Receptor

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT1A Receptor

Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility

Combined Interactions with I1-, I2-Imidazoline Binding Sites and α2-Adrenoceptors To Manage Opioid Addiction

Contact Info

Product

Resources

About

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

The Versatile 2‐Substituted Imidazoline Nucleus as a Structural Motif of Ligands Directed to the Serotonin 5‐HT_1A Receptor

Combined Interactions with I₁-, I₂-Imidazoline Binding Sites and α₂-Adrenoceptors To Manage Opioid Addiction