Related Experiment Video
Updated: May 13, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
The potential of neuronal nicotinic acetylcholine receptor agonists for treating CNS conditions
Michael W Decker1, Murali Gopalakrishnan, Michael D Meyer
1Abbott Global Pharmaceutical Research and Development, Neuroscience Drug Discovery Research, Dept. R4N5, Bldg. AP-9A/3, 100 Abbott Park Road, Abbott Park, IL 60064-6125, USA +1 847 937 2422 ; +1 847 937 9195 ; michael.w.decker@abbott.com.
Background:
Nicotine has a variety of effects in humans and in experimental animals that are suggestive of therapeutic potential. However, nicotine has a variety of adverse effects that preclude its development as a therapeutic agent, with the exception of its short-term use as a smoking cessation aide.
Objective:
In this paper, we describe the clinical evidence supporting the potential of new nicotinic acetylcholine receptor (nAChR) agonists for the treatment of CNS conditions and review discovery strategies for targeting neuronal nAChRs as well as some of the opportunities and challenges still ahead.
Method:
The scientific literature and company websites are used for this literature review.
Conclusion:
Advances in the understanding of nAChRs during the past two decades have revealed evidence of considerable subtype diversity and hence the possibility of targeted nAChR ligands as improved therapeutics. Several new nAChR agonists have advanced to Phase II clinical trials and have produced signals of efficacy in Alzheimer's disease, attention deficit hyperactivity disorder, cognitive deficits of schizophrenia and pain. In addition, the neuronal nAChR partial agonist varenicline recently received regulatory approval for use in smoking cessation.
Related Concept Videos
Cholinergic Receptors: Nicotinic
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
Indirect-Acting Cholinergic Agonists: Pharmacological Actions
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
Direct-Acting Cholinergic Agonists: Pharmacological Actions
Direct-Acting Cholinergic Agonists: Therapeutic Uses
Direct-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
The direct-acting...
Drugs Acting on Autonomic Ganglia: Stimulants
Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
