Milameline (CI-979, PD-129,409, RU-35,926) is a
non-selective
In biochemistry and pharmacology, a ligand is a Chemical substance, substance that forms a Complex (chemistry), complex with a biomolecule to serve a biological purpose. The etymology stems from ''ligare'', which means 'to bind'. In protein-lig ...
muscarinic acetylcholine receptor
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...
partial agonist
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 e ...
with
cognition
Cognition refers to "the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses". It encompasses all aspects of intellectual functions and processes such as: perception, attention, thought, ...
-acting properties that was being investigated for the treatment of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, but produced poor results in
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
s and was subsequently discontinued.
*Changing the ''O''-methyl aldoxime to an ''O''-
propargyl
In organic chemistry, the propargyl group is a functional group of 2-propynyl with the structure . It is an alkyl group derived from propyne ().
The term propargylic refers to a saturated position ( ''sp''3-hybridized) on a molecular framework n ...
oxime instead gives a separate molecule called
RU 35986.
See also
*
Alvameline
Alvameline (Lu 25-109) is a M1 receptor agonist and M2/ M3 receptor antagonist that was under investigation for the treatment of Alzheimer's disease, but produced poor results in clinical trials and was subsequently discontinued.
Synthesis ...
*
Sabcomeline
Sabcomeline (Memric; SB-202,026) is a selective M1 receptor partial agonist that was under development for the treatment of Alzheimer's disease. It made it to phase III clinical trials before being discontinued due to poor results.
See also ...
*
Tazomeline
Tazomeline (LY-287,041) is a drug which acts as a non- selective muscarinic acetylcholine receptor agonist. It was in clinical trials for the treatment of cognitive dysfunction such as that seen in Alzheimer's disease and schizophrenia, but de ...
*
Xanomeline
Xanomeline (LY-246,708; Lumeron, Memcor) is a small molecule muscarinic acetylcholine receptor agonist that was first synthesized in a collaboration between Eli Lilly and Novo Nordisk as an investigational therapeutic being studied for the treatme ...
References
{{Muscarinic acetylcholine receptor modulators
Muscarinic agonists
Aldoximes
Tetrahydropyridines