Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers

@article{Dunbar2006EffectsOT,
  title={Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers},
  author={Geoffrey C. Dunbar and Peter H. Boeijinga and Agn{\`e}s Demazi{\`e}res and Claire Cisterni and Ramana V Kuchibhatla and K. Wesnes and R{\'e}my Luthringer},
  journal={Psychopharmacology},
  year={2006},
  volume={191},
  pages={919-929}
}
ObjectivesThe aim of this study was to get insight into the central effects of TC-1734 (renamed AZD3480), a selective agonist at the neuronal nicotinic receptor of the α4β2 subtype.Materials and methodsElectroencephalography (EEG) techniques and computerized cognitive tests were performed in young, healthy male volunteers during two double-blind and placebo-controlled studies: a rising single dose crossover study (from 2 to 320 mg) and a rising repeated dose study with a parallel group design… 
An acute dose, randomized trial of the effects of CDP-Choline on Mismatch Negativity (MMN) in healthy volunteers stratified by deviance detection level
TLDR
Preliminary findings of improved auditory deviance detection with CDP-choline in a biomarker-defined healthy surrogate group supports the contention that α7 nicotinic cholinergic agonism be studied as a potential pro-cognitive mechanism in patients with schizophrenia.
Assessment of the effects of AZD3480 on cognitive function in patients with schizophrenia
Acute effects of mecamylamine and varenicline on cognitive performance in non-smokers with and without schizophrenia
TLDR
Findings support a role for nAChRs in attention and suggest that those with schizophrenia may be particularly sensitive to nA ChR blockade.
Effects of chronic sazetidine-A, a selective α4β2 neuronal nicotinic acetylcholine receptors desensitizing agent on pharmacologically-induced impaired attention in rats
TLDR
The results indicate that the desensitization of α4β2 nicotinic receptors with some activation of these receptors may play an important role in improving effects of sazetidine-A on attention.
CDP-choline and galantamine, a personalized α7 nicotinic acetylcholine receptor targeted treatment for the modulation of speech MMN indexed deviance detection in healthy volunteers: a pilot study
TLDR
Increases in MMN generation mediated by the acute CDP-choline/galantamine treatment in individuals with low baseline MMN amplitude for frequency, intensity, duration, and vowel deviants were revealed.
A randomized, double-blind, placebo-controlled crossover study of α4β2* nicotinic acetylcholine receptor agonist AZD1446 (TC-6683) in adults with attention-deficit/hyperactivity disorder
TLDR
The present study does not support the therapeutic utility of AZD1446 in ADHD, but its potential pro-cognitive effects remain to be explored in other neuropsychiatric disorders.
Effects of AZD3480 on cognition in patients with mild-to-moderate Alzheimer's disease: a phase IIb dose-finding study.
TLDR
The study did not meet proof of concept criteria: since neither AZD3480 nor donepezil were statistically significantly superior to placebo on ADAS-Cog and was considered to be inconclusive.
A randomized double-blind study comparing 25 and 50 mg TC-1734 (AZD3480) with placebo, in older subjects with age-associated memory impairment
TLDR
It can be concluded the compound likely had a beneficial effect on cognition after all three co-primary outcomes were positive and appeared safe and well tolerated in this study.
...
...

References

SHOWING 1-10 OF 50 REFERENCES
Brain-selective stimulation of nicotinic receptors by TC-1734 enhances ACh transmission from frontoparietal cortex and memory in rodents
TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects.
TLDR
The bioavailability, pharmacological, pharmacokinetic, and safety profile of TC-1734 provides an example of a safe, potent and efficacious neuronal nicotinic modulator that holds promise for the management of the hallmark symptomatologies observed in dementia.
Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI)
TLDR
Early results demonstrate ispronicline was well tolerated and did not display the side effects typical of nicotine, and was seen most strongly in a Cmax range that had been predicted from pre-clinical animal studies.
Acute effects of the selective cholinergic channel activator (nicotinic agonist) ABT-418 in Alzheimer’s disease
TLDR
It is confirmed that stimulating central nicotinic receptors has acute cognitive benefit in AD patients and suggested that selective ChCAs have a potential therapeutic role in dementing disorders, and that further studies with this or similar agents in AD and/or Parkinson’s disease are warranted.
Pharmacokinetics and Safety Profile of Ispronicline (TC‐1734), a New Brain Nicotinic Receptor Partial Agonist, in Young Healthy Male Volunteers
TLDR
Across the dose ranges explored, TC‐1734 was safe and well tolerated, and no changes of clinical significance were seen on laboratory and cardiovascular parameters.
Cognitive enhancement in man with ispronicline, a nicotinic partial agonist
TLDR
In animal models ispronicline potently improved cognitive function and has no detectable effects on muscle or ganglionic nAChRs, indicating a marked CNS over PNS selectivity.
Acute Nicotine Administration in Alzheimer’s Disease: An Exploratory EEG Study
TLDR
Although postnicotine EEG indices remained within the abnormal range, nicotine, compared to placebo, significantly shifted EEG towards normal values by reducing slow wave (relative delta and theta) power and augmenting fast (relative alpha-1, alpha-2, beta-1) wave power.
Chronic inhibition of α4β2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response
TLDR
The ability of nicotine to attenuate the impairment supports the development of nicotinic agonist therapy of syndromes, such as Alzheimer's disease, that involve a chronic decrease in the activity of the α4β2 Nicotinic receptors and memory impairment.
Safety, Pharmacokinetics, and Effects on Cognitive Function of Multiple Doses of GTS-21 in Healthy, Male Volunteers*
TLDR
Data indicate that GTS-21 may represent a novel treatment for dementia, and shows statistically significant enhancement of three measures of cognitive function compared to placebo.
Short-term effects of acetylcholinesterase inhibitor treatment on EEG and memory performance in Alzheimer patients: an open, controlled trial.
INTRODUCTION Acetylcholinesterase inhibitor treatment enhances cholinergic neurotransmission and may thus partially reverse EEG slowing and memory impairment in Alzheimer patients within short time.
...
...