102,432 research outputs found
The Camerino symposium series (1978-2013): a privileged observatory of receptorology development
No full textThe organizers of the Camerino Receptor Symposia survey the development of receptorology. They trace the
course from the first Symposium in 1978, which laid the foundation for Pirenzepine, the first selective muscarinic
antagonist, to the 2010 Symposium, which highlighted the utility of functional simple domain antibodies
(nanobodies) as novel G Protein-Coupled Receptor (GPCR) modulators. This 30-year period sees the acceptance of
terms such as G-protein, auto- and heteroreceptors, site-directed mutagenesis, chimeric receptors, constitutive
activity, inverse agonism, and orphan receptors. GPCRs are finally a reality and Langley and Ehrlich, if they returned
to their laboratories, would be proud of how their intuitions have been realized
Irreversible alfa-adrenoceptor blocking effects and irreversible muscarinic blocking and nicotinic blocking effect of tetramine disulfides on heart B. G. Benfey, B. Belleau, L. Brasili, M. Giannella, C. Melchiorre
No full textInotropic effects of phenylephrine'-carbachol' and butyryrchorine were used in rabbit reft atrium to evaluate respectively, apha receptor blocking, muscarinic blocking and nicotinic blocking effect of tetramine disulfide. The alpha adrenergic blocking potency of newly synthetized derivatives were similar to those with an o-methoxy-benzyl group. Muscarinic and nicotinic blocking potency were correlated with the alpha adrenergic blocking potency
From benzodioxane to 1,4-dioxane scaffold in the design of 5-HT1A serotoninergic full agonists from α1-adrenergic antagonists
No full textThe quite planar 1,4-benzodioxane structure of the non-subtype selective α1-adrenergic antagonist WB 4101 (1) [1] has successfully been replaced by the less conformationally
constrained 1,4-dioxane nucleus substituted in its positions 5 or 6 with one or two pendant phenyl rings. Indeed, the compounds characterized by N-(6,6-diphenyl-1,4dioxan-2ylmethyl)-2-phenoxyethanamine structure, where R is 2,6-OCH3 (2), 2-OCH3 (3), or H (4), showed full 5-HT1A receptor agonism, selective α1D-adrenergic antagonism or significant cytotoxic activity, respectively [2]. Considering that a high degree of homology exits between 5-HT1A and α1-adrenergic receptors [3] and WB 4101 itself displays 5-HT1A affinity, the improved 5-HT1A/α1-adrenergic profile of compound 2 appeared noteworthy. Therefore, to identify stereochemical requirements for the selective recognition of the above mentioned biological targets, the derivatives 2-4 have been resolved into the corresponding enantiomers. In addition, novel ligands, bearing one or two phenyl groups in positions 2 or 3 of the 1,4-dioxane scaffold, have been prepared and studied.
References
[1]. Mottram, D. R.; Kapur, H. J. Pharm. Pharmacol., 27, 295-296, 1975.
[2]. Quaglia, W.; Piergentili, A.; Del Bello, F.; Farande, Y.; Giannella, M.; Pigini, M.; Rafaiani, G.; Carrieri, A.; Amantini, C.; Lucciarini, R.; Santoni, G.; Poggesi, E.; Leonardi, A. J. Med. Chem., 51, 6359-6370, 2008.
[3]. Trumpp-Kallmeyer, S.; Hoflack, J.; Bruinvels, A.; Hibert, M. J. Med. Chem., 35, 3448-3462, 1992
I farmaci convenzionali senza prescrizione medica. Dai consigli del farmacista alle pratiche di automedicazione
No full textIl presente contributo si discutono gli esiti della ricerca in relazione alle domande sul consumo di farmaci convenzionali senza prescrizione medica.
Dopo una breve ricognizione della letteratura scientifica prodotta sul tema a livello internazionale (§ 1), il capitolo indaga le modalità di assunzione in termini di frequenza d’uso e indicazioni terapeutiche (§ 2), le motivazioni e i processi di acquisto (§ 3), le modalità di assunzione ed i benefici percepiti (§ 4), in relazione alle principali variabili socio-demografiche
Enantiomers of 6,6-diphenyl-1,4-dioxane derivatives to highlight stereochemical requirements for selective alpha1D-AR and 5- HT1A receptor recognition
No full textSeveral examples support the concept that modest chemical modifications can drastically alter the biological profile of the compounds both regard to different receptor systems and inside the same system, leading to unexpected and interesting results. This consideration has prompted Boström et al. to question whether structurally similar ligands bind in a similar fashion.1
In a recent study about new 6,6-diphenyl-1,4-dioxane derivatives, we demonstrated that small modifications on the 2-phenoxyethyl moiety induced significant biological changes. In fact, the unsubstituted 1, the 2-methoxy 2, and the 2,6-dimethoxy 3 analogues proved to be endowed with high cytotossic effect, α1D-adrenergic receptor (α1D-AR) antagonist and 5-HT1A receptor full agonist activity, respectively.2
It is well known that stereochemistry can quantitatively and qualitatively influence ligand biological profile3 and that α1D- and 5-HT1A receptor interactions result highly stereospecific. Therefore, to obtain indications for identifying further structural and stereochemical requirements for selective α1D and 5-HT1A receptor recognition, we thought it of interest to prepare and test the enantiomers of 2 and 3. The enantiomers of 1 have been prepared to verify whether there is a relationship between stereochemistry and anticancer activity.
1. Boström, J.; Hogner, A.; Schmitt, S. Do structurally similar ligands bind in a similar fashion? J. Med. Chem. 2006, 49, 6716-6725.
2. Quaglia, W.; Piergentili, A.; Del Bello, F.; Farande, Y.; Giannella, M.; Pigini, M.; Rafaiani, G.; Carrieri, A.; Amantini, C.; Lucciarini, R.; Santoni, G.; Poggesi, E.; Leonardi, A. Structure-activity relationships in 1,4-benzodioxan-related compounds. 9. From 1,4-benzodioxan to 1,4-dioxane
ring as a promising template of novel α1D-adrenoreceptor antagonists, 5-HT1A full agonists, and
cytotoxic agents. J. Med. Chem. 2008, 51, 6359-6370.
3. Caner, H.; Groner, E.; Levy, L. Trends in the development of chiral drugs. Drug Disc. Today 2004, 9, 105-110
Il percorso metodologico dell'indagine
No full textIl contributo illustra la metodologia di un percorso investigativo che ha coinvolto sia i cittadini sia il personale delle farmacie, con lo scopo di prendere ad esame i percorsi di accesso alle terapie farmacologiche, su cui influisce, da un lato, una diffusa cultura dell’automedicazione, dall’altro, la fiducia verso approcci alternativi e complementari rispetto alla medicina a base scientifica. I risultati consentono di tracciare nuove prospettive interpretative sulla tutela della salute nella società contemporanea
Leader's morality, prototypicality, and followers’ reactions
No full textWe examine the effects of moral (vs. competent) leadership on followers' leader evaluations and endorsement. In Study 1 (N = 157), followers evaluated a leader more negatively and endorsed them less when they failed on morality than competence. An indirect effect from leader morality to leader evaluation, through perceived group prototypicality emerged, demonstrating the identity-basis of this evaluation. In Studies 2 (N = 150), 3 (N = 297), and 4 (N = 192) participants considered incongruous situations in which the leader failed on morality but succeed on competence, or vice-versa. Followers expressed more negative evaluations and less endorsement of an immoral but competent leader than of a moral but incompetent leader, through group prototypicality. In Study 4, we manipulated group prototypicality. A leader considered prototypical of the group received worse evaluations when they behaved immorally, irrespective of their competence. Results contribute to the understanding of leader-followers dynamics
Dual boundary element method and finite element method for mixed-mode crack propagation simulations in a cracked hollow shaft
No full textThree-dimensional mixed-mode crack propagation simulations were performed by means of the dual boundary element method code BEASY and 2 finite element method-based crack propagation codes: ZENCRACK (ZC) and CRACKTRACER3D (CT3D). The stress intensity factors (SIFs) along the front of an initial semielliptical crack, initiated from the external surface of a shaft, were calculated for 4 different load cases: bending, press fit, shear, and torsion. The methods used for the SIF assessment along the crack front were the J-integral for BEASY and ZC and the quarter point element stress method for CT3D. Subsequently, crack propagation simulations were performed, with the crack growth rate evaluated by using Paris' law, calibrated for the material at stake (American Society for Testing and Materials A469 steel). The kink angles were evaluated by using the minimum strain energy density and maximum tangential stress criteria for BEASY, the maximum energy release rate and maximum tangential stress for ZC, and the maximum principal asymptotic stress for CT3D. The results obtained in terms of SIFs and crack propagation life show very good agreement among the 3 codes. Also, the shape of the propagated crack, which is significantly out-of-plane for the shear and torsion loading, matched very well
On the effects of ethical climate(s) on employees’ behavior: a social identity approach
No full textThis is the author accepted manuscript. The final version is available from Frontiers Media via the DOI in this record.The spread and publicity given to questionable practices in the corporate world during the last two decades has fostered an increasing interest about the importance of ethical work for organizations, practitioners, scholars and, last but not least, the wider public. Relying on the Social Identity Approach, we suggest that the effects of different ethical climates on employee behaviors are driven by affective identification with the organization and, in parallel, by cognitive moral (dis)engagement. We compared the effects of two particular ethical climates derived from the literature: An ethical organizational climate of self-interest, and an ethical organizational climate of friendship. Three hundred seventy-six workers completed measures of Ethical Climate, Organizational Identification, Moral Disengagement, Organizational Citizenship Behaviors, and Counterproductive Work Behaviors. Structural equation modelling confirmed that the two ethical climates considered were independently related to organizational identification and moral disengagement. These, in turn, mediated the effects of ethical climates on Organizational Citizenship Behaviors and Counterproductive Work Behaviors. We discuss results in light of the social identity approach, and present some practical implications of our findings
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