Himbacine is an alkaloid isolated from the bark of
Australian magnolias. Himbacine has been synthesized using a
Diels-Alder reaction as a key step.
Himbacine's activity as a
muscarinic
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 ...
receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...
, with specificity for the
muscarinic acetylcholine receptor M2
The muscarinic acetylcholine receptor M2, also known as the cholinergic receptor, muscarinic 2, is a muscarinic acetylcholine receptor that in humans is encoded by the ''CHRM2'' gene. Multiple alternatively spliced transcript variants have been ...
, made it a promising starting point in
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 ...
research.
The development of a muscarinic antagonist based on himbacine failed but an analog,
vorapaxar, has been approved by the
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
as a
thrombin receptor antagonist.
References
Muscarinic antagonists
Naphthofurans
Piperidine alkaloids
Lactones
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