scholarly journals Announcing the novel class of GABA–A receptor selective positive allosteric modulator antidepressants

2021 ◽  
Vol 7 (2) ◽  
pp. FSO654
Author(s):  
Olumuyiwa John Fasipe ◽  
Olalekan Ayodele Agede ◽  
Adenike Christiana Enikuomehin
Keyword(s):  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator ◽  
Gaba A

scholarly journals AZD-3043

2012 ◽  
Vol 116 (6) ◽  
pp. 1267-1277 ◽  
Author(s):  
Talmage D. Egan ◽  
Shinju Obara ◽  
Thomas E. Jenkins ◽  
Sarah S. Jaw-Tsai ◽  
Shanti Amagasu ◽  
...  
Keyword(s):  
Dynamic Model ◽  
Metabolic Pathway ◽  
Liver Microsomes ◽  
Allosteric Modulator ◽  
Positive Allosteric Modulator ◽  
Duration Of Action ◽  
Chloride Currents ◽  
Gaba A ◽  
Hypnotic Agent

Background Propofol can be associated with delayed awakening after prolonged infusion. The aim of this study was to characterize the preclinical pharmacology of AZD-3043, a positive allosteric modulator of the γ-aminobutyric acid type A (GABA(A)) receptor containing a metabolically labile ester moiety. The authors postulated that its metabolic pathway would result in a short-acting clinical profile. Methods The effects of AZD-3043, propofol, and propanidid were studied on GABA(A) receptor-mediated chloride currents in embryonic rat cortical neurons. Radioligand binding studies were also performed. The in vitro stability of AZD-3043 in whole blood and liver microsomes was evaluated. The duration of the loss of righting reflex and effects on the electroencephalograph evoked by bolus or infusion intravenous administration were assessed in rats. A mixed-effects kinetic-dynamic model using minipigs permitted exploration of the clinical pharmacology of AZD-3043. Results AZD-3043 potentiated GABA(A) receptor-mediated chloride currents and inhibited [(35)S]tert-butylbicyclophosphorothionate binding to GABA(A) receptors. AZD-3043 was rapidly hydrolyzed in liver microsomes from humans and animals. AZD-3043 produced hypnosis and electroencephalograph depression in rats. Compared with propofol, AZD-3043 was shorter acting in rats and pigs. Computer simulation using the porcine kinetic-dynamic model demonstrated that AZD-3043 has very short 50 and 80% decrement times independent of infusion duration. Conclusions AZD-3043 is a positive allosteric modulator of the GABA(A) receptor in vitro and a sedative-hypnotic agent in vivo. The esterase dependent metabolic pathway results in rapid clearance and short duration of action even for long infusions. AZD-3043 may have clinical potential as a sedative-hypnotic agent with rapid and predictable recovery.

Efficacy and side effects of baclofen and the novel GABAB receptor positive allosteric modulator CMPPE in animal models for alcohol and cocaine addiction

2018 ◽  
Vol 235 (7) ◽  
pp. 1955-1965 ◽  
Author(s):  
Valentina Vengeliene ◽  
Tatiane T. Takahashi ◽  
Olga A. Dravolina ◽  
Irina Belozertseva ◽  
Edwin Zvartau ◽  
...  
Keyword(s):  
Side Effects ◽  
Animal Models ◽  
Gabab Receptor ◽  
Cocaine Addiction ◽  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator

Characterization of the Novel Positive Allosteric Modulator, LY2119620, at the Muscarinic M2and M4Receptors

2014 ◽  
Vol 86 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Carrie H. Croy ◽  
Douglas A. Schober ◽  
Hongling Xiao ◽  
Anne Quets ◽  
Arthur Christopoulos ◽  
...  
Keyword(s):  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator

[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

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

scholarly journals Pharmacology in translation: the preclinical and early clinical profile of the novel α2/3 functionally selective GABAA receptor positive allosteric modulator PF-06372865

2018 ◽  
Vol 175 (4) ◽  
pp. 708-725 ◽  
Author(s):  
Sarah A Nickolls ◽  
Rachel Gurrell ◽  
Guido van Amerongen ◽  
Juha Kammonen ◽  
Lishuang Cao ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Clinical Profile ◽  
Allosteric Modulator ◽  
The Novel ◽  
Positive Allosteric Modulator
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