Evidence for alpha7 nicotinic receptor activation during the cough suppressing effects induced by nicotine and identification of ATA-101 as a potential novel therapy for the treatment of chronic cough

2021 ◽  
pp. JPET-AR-2021-000641
Author(s):  
Brendan J. Canning ◽  
Qi Liu ◽  
Mayuko Tao ◽  
Robert DeVita ◽  
Michael Perelman ◽  
...  
Keyword(s):  
Chronic Cough ◽  
Nicotinic Receptor ◽  
Receptor Activation ◽  
Novel Therapy ◽  
Alpha7 Nicotinic Receptor

First in human trial of a type I positive allosteric modulator of alpha7-nicotinic acetylcholine receptors: Pharmacokinetics, safety, and evidence for neurocognitive effect of AVL-3288

2017 ◽  
Vol 31 (4) ◽  
pp. 434-441 ◽  
Author(s):  
Kelvin W Gee ◽  
Ann Olincy ◽  
Richard Kanner ◽  
Lynn Johnson ◽  
Derk Hogenkamp ◽  
...  
Keyword(s):  
Nicotinic Acetylcholine Receptors ◽  
Nicotinic Receptor ◽  
Human Subjects ◽  
Receptor Activation ◽  
Auditory Evoked Potential ◽  
Type I ◽  
Healthy Human ◽  
Double Blind ◽  
Alpha7 Nicotinic Receptor ◽  
Neurocognitive Effect

Type I positive allosteric modulators (PAMs) of the alpha7-nicotinic receptor enhance its cholinergic activation while preserving the spatiotemporal features of synaptic transmission and the receptor’s characteristic rapid desensitization kinetics. Alpha7-nicotinic receptor agonists have shown promise for improving cognition in schizophrenia, but longer-term trials have been disappointing. Therefore, the type I PAM AVL-3288 was evaluated for safety and preliminary evidence of neurocognitive effect in healthy human subjects. Single-dose oral administration in ascending doses was conducted in a double-blind, placebo-controlled Phase I trial in non-smokers. The trial found indication of positive but non-significant effects on neurocognition at 10 and 30 mg, two doses that produced overlapping peak levels. There was also some evidence for effects on inhibition of the P50 auditory evoked potential to repeated stimuli, a biomarker that responds to alpha7-nicotinic receptor activation. The pharmacokinetic characteristics were consistent between subjects, and there were no safety concerns. The effects and safety profile were also assessed at 3 mg in a cohort of smokers, in whom concurrent nicotine administration did not alter either effects or safety. The trial demonstrates that a type I PAM can be safely administered to humans and that it has potential positive neurocognitive effects in central nervous system (CNS) disorders.

Alpha7 nicotinic receptor activation protects against oxidative stress via heme-oxygenase I induction

2015 ◽  
Vol 97 (4) ◽  
pp. 473-481 ◽  
Author(s):  
Elisa Navarro ◽  
Izaskun Buendia ◽  
Esther Parada ◽  
Rafael León ◽  
Pidder Jansen-Duerr ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Nicotinic Receptor ◽  
Receptor Activation ◽  
Alpha7 Nicotinic Receptor

Nicotinic receptor activation in perirhinal cortex and hippocampus enhances object memory in rats

2012 ◽  
Vol 62 (5-6) ◽  
pp. 2096-2105 ◽  
Author(s):  
Ashley M. Melichercik ◽  
Kevin S. Elliott ◽  
Cristina Bianchi ◽  
Sarah M. Ernst ◽  
Boyer D. Winters
Keyword(s):  
Nicotinic Receptor ◽  
Perirhinal Cortex ◽  
Receptor Activation ◽  
Object Memory
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