3-Aminomethyl Derivatives of 2-Phenylimidazo[1,2-a]-pyridine as Positive Allosteric Modulators of GABAA Receptor with Potential Antipsychotic Activity

2017 ◽  
Vol 8 (6) ◽  
pp. 1291-1298 ◽  
Author(s):  
Monika Marcinkowska ◽  
Marcin Kołaczkowski ◽  
Krzysztof Kamiński ◽  
Adam Bucki ◽  
Maciej Pawłowski ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Allosteric Modulators ◽  
Antipsychotic Activity ◽  
Aminomethyl Derivatives ◽  
Positive Allosteric Modulators ◽  
Derivatives Of

Synthesis and Biological Activity of Allosteric Modulators of GABAB Receptors, Part 1. N-(Phenylpropyl)-1-arylethylamines

2006 ◽  
Vol 59 (7) ◽  
pp. 445 ◽  
Author(s):  
David I. B. Kerr ◽  
Jennifer Ong ◽  
Michael V. Perkins ◽  
Rolf H. Prager ◽  
Ni Made Puspawati
Keyword(s):  
Biological Activity ◽  
Gabab Receptors ◽  
Allosteric Modulators ◽  
Positive Allosteric Modulators ◽  
Derivatives Of

A series of 15 analogues of fendiline, and 34 derivatives of N-(3-phenylpropyl)-1-arylethylamine have been prepared for evaluation as positive allosteric modulators of GABAB receptors. The most active (EC50, 10 nM) was N-(3,3-diphenylpropyl)-1-(3-chloro-4-methoxyphenyl)ethylamine 6g.

scholarly journals Multi-Target Approach for Drug Discovery against Schizophrenia

2018 ◽  
Vol 19 (10) ◽  
pp. 3105 ◽  
Author(s):  
Magda Kondej ◽  
Piotr Stępnicki ◽  
Agnieszka A. Kaczor
Keyword(s):  
Ampa Receptors ◽  
Drug Targets ◽  
Dopamine D2 Receptor ◽  
D2 Receptor ◽  
Binding Pocket ◽  
New Drugs ◽  
Allosteric Modulators ◽  
Single Target ◽  
Antipsychotic Activity ◽  
Positive Allosteric Modulators

Polypharmacology is nowadays considered an increasingly crucial aspect in discovering new drugs as a number of original single-target drugs have been performing far behind expectations during the last ten years. In this scenario, multi-target drugs are a promising approach against polygenic diseases with complex pathomechanisms such as schizophrenia. Indeed, second generation or atypical antipsychotics target a number of aminergic G protein-coupled receptors (GPCRs) simultaneously. Novel strategies in drug design and discovery against schizophrenia focus on targets beyond the dopaminergic hypothesis of the disease and even beyond the monoamine GPCRs. In particular these approaches concern proteins involved in glutamatergic and cholinergic neurotransmission, challenging the concept of antipsychotic activity without dopamine D2 receptor involvement. Potentially interesting compounds include ligands interacting with glycine modulatory binding pocket on N-methyl-d-aspartate (NMDA) receptors, positive allosteric modulators of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, positive allosteric modulators of metabotropic glutamatergic receptors, agonists and positive allosteric modulators of α7 nicotinic receptors, as well as muscarinic receptor agonists. In this review we discuss classical and novel drug targets for schizophrenia, cover benefits and limitations of current strategies to design multi-target drugs and show examples of multi-target ligands as antipsychotics, including marketed drugs, substances in clinical trials, and other investigational compounds.

scholarly journals Abuse-related effects of subtype-selective GABAA receptor positive allosteric modulators in an assay of intracranial self-stimulation in rats

2017 ◽  
Vol 234 (14) ◽  
pp. 2091-2101 ◽  
Author(s):  
Kathryn L. Schwienteck ◽  
Guanguan Li ◽  
Michael M. Poe ◽  
James M. Cook ◽  
Matthew L. Banks ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Allosteric Modulators ◽  
Positive Allosteric Modulators ◽  
Subtype Selective ◽  
Self Stimulation

Assessment of the effects of NS11394 and L-838417, α2/3 subunit-selective GABAA receptor-positive allosteric modulators, in tests for pain, anxiety, memory and motor function

2012 ◽  
Vol 23 (8) ◽  
pp. 790-801 ◽  
Author(s):  
Martine Hofmann ◽  
Krisztina Sz. Kordás ◽  
Andreas Gravius ◽  
Kata Bölcskei ◽  
Chris G. Parsons ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Motor Function ◽  
Allosteric Modulators ◽  
Pain Anxiety ◽  
Positive Allosteric Modulators

scholarly journals Synthesis and Biological Evaluation of Pyrroloindolines as Positive Allosteric Modulators of the α1β2γ2 GABAA Receptor

2020 ◽  
Vol 11 (11) ◽  
pp. 2204-2211
Author(s):  
Annet E. M. Blom ◽  
Justin Y. Su ◽  
Lindsay M. Repka ◽  
Sarah E. Reisman ◽  
Dennis A. Dougherty
Keyword(s):  
Gabaa Receptor ◽  
Biological Evaluation ◽  
Allosteric Modulators ◽  
Positive Allosteric Modulators ◽  
Synthesis And Biological Evaluation
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