a(CHEBI:physostigmine)

Entity

Name

physostigmine

Namespace

chebi

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/chebi-names.belns

This file encodes the article Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function by Albuquerque et al, 2009

Surprisingly, however, activation of nAChRs by galantamine or physostigmine was insensitive to blockade by competitive nAChR antagonists, was detected even when the receptors were desensitized by high agonist concentrations, and was inhibited by the monoclonal antibody FK1 (350, 370, 372, 413, 428, 429). PubMed:19126755

Surprisingly, however, activation of nAChRs by galantamine or physostigmine was insensitive to blockade by competitive nAChR antagonists, was detected even when the receptors were desensitized by high agonist concentrations, and was inhibited by the monoclonal antibody FK1 (350, 370, 372, 413, 428, 429). PubMed:19126755

An alternative means to increase nicotinic functions in the brain is to sensitize the nAChRs to activation by the endogenous agonist(s) using the so-called nicotinic allosteric potentiating ligands (APLs), which include drugs such as physostigmine and galantamine, a drug currently approved for the treatment of AD. PubMed:19126755

Studies from the early 1980s provided evidence that the cholinesterase (ChE) inhibitor physostigmine could interact directly with nAChRs at the frog neuromuscular junction and induce nicotinic single-channel currents (428, 429). PubMed:19126755

Surprisingly, however, activation of nAChRs by galantamine or physostigmine was insensitive to blockade by competitive nAChR antagonists, was detected even when the receptors were desensitized by high agonist concentrations, and was inhibited by the monoclonal antibody FK1 (350, 370, 372, 413, 428, 429). PubMed:19126755

Notably, reports that physostigmine and oral anticholinesterases have beneficial effects for patients with AD suggest that the CBF system is somewhat preserved during the progression of dementia, despite well-documented loss of cholinergic biosynthetic machinery (including ChAT and AChE enzyme deficits) in patients with this disease. Interestingly, recent studies have shown that ChAT activity, which results in acetylcholine (ACh) synthesis, is preserved in the neocortex of people with MCI [18,19]. PubMed:18986241