Pozanicline (
INN
Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...
,
codenamed ABT-089) is a drug developed by
Abbott, that has
nootropic
Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote re ...
and
neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal los ...
effects. Animal studies suggested it useful for the treatment of
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inapp ...
and subsequent human trials have shown ABT-089 to be effective for this application. It binds with high affinity
subtype-selective to the
α4β2 nicotinic acetylcholine receptors
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral n ...
and has
partial agonism
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic ef ...
to the
α6β2 subtype,
but not the
α7 and
α3β4 subtypes familiar to nicotine. It has particularly low tendency to cause side effects compared to other drugs in the class, making it an exciting candidate for clinical development.
Synthesis
Pozanicline is synthesized from 2-methyl-3-hydroxypyridine and Boc-L-Prolinol through a dehydration reaction followed by deprotection of the nitrogen atom of prolinol
References
{{Nicotinic acetylcholine receptor modulators
Nicotinic agonists
Nootropics
Phenol ethers
Pyridines
Pyrrolidines
Stimulants