scholarly journals In Vivo Non-radioactive Assessment of mGlu5 Receptor-Activated Polyphosphoinositide Hydrolysis in Response to Systemic Administration of a Positive Allosteric Modulator

2018 ◽  
Vol 9 ◽  
Author(s):  
Anna R. Zuena ◽  
Luisa Iacovelli ◽  
Rosamaria Orlando ◽  
Luisa Di Menna ◽  
Paola Casolini ◽  
...  
Keyword(s):  
Systemic Administration ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Mglu5 Receptor

In vitro and in vivo characterization of PheTQS, a novel α7 nAChR positive allosteric modulator

2009 ◽  
Vol 78 (7) ◽  
pp. 913 ◽  
Author(s):  
James N.C. Kew ◽  
Selina Mok ◽  
Annette Weil ◽  
Caterina Virginio ◽  
Laura Castelletti ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Α7 Nachr ◽  
In Vivo Characterization

scholarly journals In Silico Identification and Experimental Validation of (−)-Muqubilin A, a Marine Norterpene Peroxide, as PPARα/γ-RXRα Agonist and RARα Positive Allosteric Modulator

Marine Drugs ◽  
2019 ◽  
Vol 17 (2) ◽  
pp. 110 ◽  
Author(s):  
Enrico D’Aniello ◽  
Fabio Iannotti ◽  
Lauren Falkenberg ◽  
Andrea Martella ◽  
Alessandra Gentile ◽  
...  
Keyword(s):  
Binding Mode ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Full Agonist ◽  
Synergistic Enhancement ◽  
Pharmacological Targets ◽  
In Vivo Analysis ◽  
Dynamics Simulations ◽  
Micromolar Range

The nuclear receptors (NRs) RARα, RXRα, PPARα, and PPARγ represent promising pharmacological targets for the treatment of neurodegenerative diseases. In the search for molecules able to simultaneously target all the above-mentioned NRs, we screened an in-house developed molecular database using a ligand-based approach, identifying (−)-Muqubilin (Muq), a cyclic peroxide norterpene from a marine sponge, as a potential hit. The ability of this compound to stably and effectively bind these NRs was assessed by molecular docking and molecular dynamics simulations. Muq recapitulated all the main interactions of a canonical full agonist for RXRα and both PPARα and PPARγ, whereas the binding mode toward RARα showed peculiar features potentially impairing its activity as full agonist. Luciferase assays confirmed that Muq acts as a full agonist for RXRα, PPARα, and PPARγ with an activity in the low- to sub-micromolar range. On the other hand, in the case of RAR, a very weak agonist activity was observed in the micromolar range. Quite surprisingly, we found that Muq is a positive allosteric modulator for RARα, as both luciferase assays and in vivo analysis using a zebrafish transgenic retinoic acid (RA) reporter line showed that co-administration of Muq with RA produced a potent synergistic enhancement of RARα activation and RA signaling.

In vitro and in vivo pharmacological characterization of SSD114, a novel GABAB positive allosteric modulator

2016 ◽  
Vol 791 ◽  
pp. 115-123 ◽  
Author(s):  
Alessandra Porcu ◽  
Carla Lobina ◽  
Daniela Giunta ◽  
Maurizio Solinas ◽  
Claudia Mugnaini ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Pharmacological Characterization

scholarly journals A 5-mer peptide derived from hinge region of hFSHR can function as positive allosteric modulator in vivo

2021 ◽  
Vol 1863 (1) ◽  
pp. 183492
Author(s):  
Kaushiki S. Prabhudesai ◽  
Muthu Sankar Aathi ◽  
Vikas Dighe ◽  
Susan Idicula-Thomas
Keyword(s):  
Hinge Region ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator

scholarly journals The In Vivo Effects of the CB1-Positive Allosteric Modulator GAT229 on Intraocular Pressure in Ocular Normotensive and Hypertensive Mice

2017 ◽  
Vol 33 (8) ◽  
pp. 582-590 ◽  
Author(s):  
Elizabeth A. Cairns ◽  
Anna-Maria Szczesniak ◽  
Alex J. Straiker ◽  
Pushkar M. Kulkarni ◽  
Roger G. Pertwee ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
In Vivo Effects

[P4-036]: THE NOVEL AMPA RECEPTOR POSITIVE ALLOSTERIC MODULATOR S 47445 RESCUES IN VIVO CA3-CA1 LONG-TERM POTENTIATION AND STRUCTURAL SYNAPTIC CHANGES IN MIDDLE-AGED MICE

2017 ◽  
Vol 13 (7S_Part_26) ◽  
pp. P1270-P1270
Author(s):  
Sylvie Bretin ◽  
Albert Giralt ◽  
María Ángeles Gómez-Climent ◽  
Rafael Alcalá ◽  
Jose Maria Delgado-Garcia ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Long Term Potentiation ◽  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator ◽  
Aged Mice ◽  
Term Potentiation ◽  
Synaptic Changes

scholarly journals Effects of the Positive Allosteric Modulator of Metabotropic Glutamate Receptor 5, VU-29, on Maintenance Association between Environmental Cues and Rewarding Properties of Ethanol in Rats

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 793
Author(s):  
Marta Marszalek-Grabska ◽  
Kinga Gawel ◽  
Dariusz Matosiuk ◽  
Ewa Gibula-Tarlowska ◽  
Joanna Listos ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Home Cage ◽  
Metabotropic Glutamate Receptor ◽  
Drugs Of Abuse ◽  
Inhibitory Effect ◽  
Future Research ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Metabotropic Glutamate ◽  
Mglu5 Receptor

Metabotropic glutamate subtype 5 (mGlu5) receptors are implicated in various forms of synaptic plasticity, including drugs of abuse. In drug-addicted individuals, associative memories can drive relapse to drug use. The present study investigated the potential of the mGlu5 receptor positive allosteric modulator (PAM), VU-29 (30 mg/kg, i.p.), to inhibit the maintenance of a learned association between ethanol and environmental context by using conditioned place preference (CPP) in rats. The ethanol-CPP was established by the administration of ethanol (1.0 g/kg, i.p. ×10 days) using an unbiased procedure. Following ethanol conditioning, VU-29 was administered at various post-conditioning times (ethanol free state at the home cage) to ascertain if there was a temporal window during which VU-29 would be effective. Our experiments indicated that VU-29 did not affect the expression of ethanol-induced CPP when it was given over two post-conditioning days. However, the expression of ethanol-CPP was inhibited by 10-day home cage administration of VU-29, but not by first 2-day or last 2-day injection of VU-29 during the 10-day period. These findings reveal that VU-29 can inhibit the maintenance of ethanol-induced CPP, and that treatment duration contributes to this effect of VU-29. Furthermore, VU-29 effect was reversed by pretreatment with either MTEP (the mGlu5 receptor antagonist), or MK-801 (the N-methyl-D-aspartate-NMDA receptor antagonist). Thus, the inhibitory effect of VU-29 is dependent on the functional interaction between mGlu5 and NMDA receptors. Because a reduction in ethanol-associated cues can reduce relapse, mGlu5 receptor PAM would be useful for therapy of alcoholism. Future research is required to confirm the current findings.

In vitro and in vivo characterization of the novel GABAB receptor positive allosteric modulator, 2-{1-[2-(4-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-yl]-2-piperidinyl}ethanol (CMPPE)

2011 ◽  
Vol 61 (5-6) ◽  
pp. 957-966 ◽  
Author(s):  
Elisabetta Perdona’ ◽  
Vivian J.A. Costantini ◽  
Michela Tessari ◽  
Prisca Martinelli ◽  
Corrado Carignani ◽  
...  
Keyword(s):  
Gabab Receptor ◽  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator ◽  
In Vivo Characterization
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