Pharmacokinetics and Safety Profile of Ispronicline (TC‐1734), a New Brain Nicotinic Receptor Partial Agonist, in Young Healthy Male Volunteers

  title={Pharmacokinetics and Safety Profile of Ispronicline (TC‐1734), a New Brain Nicotinic Receptor Partial Agonist, in Young Healthy Male Volunteers},
  author={Geoffrey C. Dunbar and Agn{\`e}s Demazi{\`e}res and A. M. Jiménez Monreal and Claire Cisterni and D{\'e}borah Metzger and Ramana V Kuchibhatla and R{\'e}my Luthringer},
  journal={The Journal of Clinical Pharmacology},
Recent research suggests that drugs activating nicotine acetylcholine receptors might be promising therapy in cognitive decline seen in the elderly, including Alzheimer's disease. Ispronicline (TC‐1734), a brain‐selective α4β2 nicotine acetylcholine receptor partial agonist, has shown memory‐enhancing properties in rodents and a good tolerability profile. The safety and the full pharmacokinetic profile of TC‐1734 and its N‐desalkylated metabolite, TC‐1784, were investigated in 2 phase I studies… 

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

These early data in healthy subjects provide encouragement to consider development of AZD3480 as a novel agent for the treatment of cognitive decline in the elderly, including age-associated memory impairment and/or dementia of the Alzheimer’s type.

Effects of AZD3480 on cognition in patients with mild-to-moderate Alzheimer's disease: a phase IIb dose-finding study.

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.

Recent Developments in Novel Antidepressants Targeting α4β2-Nicotinic Acetylcholine Receptors

An in-depth analysis of the potential for using nicotinic ligands in the treatment of depression, which may hold some promise in addressing an unmet clinical need by providing relief from depressive symptoms in refractory patients is provided.

Nicotinic Acetylcholine Receptor Agonists for the Treatment of Alzheimer's Dementia: An Update.

A significant portion of the clinical phenotype observed in Alzheimer's disease (AD) occurs through nicotinic acetylcholine receptors (nAChRs), and agonists of these receptors will likely exert pro-cognitive benefits through multiple mechanisms including stimulating the cholinergic pathway, modulating inflammation, and buffering the effects of amyloid.

An update on pharmacological approaches to neurodegenerative diseases

In this review, the authors intend to survey new drugs in different clinical phases but not in the preclinical or discovery stages nor already in the market, with new molecules aimed at interrupting or at attenuating different pathogenic pathways of neurodegeneration and/or at ameliorating symptoms.

Current awareness: Pharmacoepidemiology and drug safety

  • Medicine
  • 2007
The bibliography contains newly published material in the field of pharmacoepidemiology and drug safety in order to keep subscribers up‐to‐date with the latest developments in their field.

Investigational drugs for the treatment of AD: what can we learn from negative trials?

A set of molecules with a range of mechanisms that have been trialed but with negative results are reviewed and the reasons for the negative findings are examined.



TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects.

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.

A pilot controlled clinical trial of ABT-418, a cholinergic agonist, in the treatment of adults with attention deficit hyperactivity disorder.

The results of this investigation indicate that ABT-418, a nicotinic analog, may be a potentially useful agent for the treatment of ADHD.

Memantine for dementia.

A small beneficial effect of memantine at six months in moderate to severe AD is suggested and the statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect.

Memantine for dementia.

The beneficial effect on cognition in patients with mild to moderate vascular dementia was not detectable on global assessment at six months and the statistical significance of these benefits could be overturned by data from two unpublished studies which are known to show no significant effect.

Chronic inhibition of α4β2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response

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.

Nicotinic treatment of Alzheimer’s disease

Nicotinic receptors in aging and dementia.

Activation of neuronal nicotinic acetylcholine receptors (nAChRs) has been shown to maintain cognitive function following aging or the development of dementia. Nicotine and nicotinic agonists have

Increased neurodegeneration during ageing in mice lacking high‐affinity nicotine receptors

Data show that β2 subunit‐containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing, and β2−/− mice may serve as one possible animal model for some of the cognitive deficits and degenerative processes which take place during physiological ageing and in Alzheimer's disease.