Abstract：
:Tetrahydroaminoacridine (THA) has recently been reported to be more useful in the treatment of Alzheimer's disease than physostigmine. A comparison of the effects of these two anticholinesterase agents on in vitro enzyme and receptor activities of human cerebral cortex (obtained at autopsy) revealed similarities in their interactions with acetylcholinesterase (AChE) but striking differences in their ability to displace both nicotinic and muscarinic radioligands from membrane preparations. IC50 values (the concentration required to reduce enzyme activity by 50%) for the inhibition of total tissue AChE were 7.9 x 10(-7) M and 4.5 x 10(-8) M for THA and physostigmine, respectively, and similar values were also obtained for individual molecular forms of AChE (monomer G1, dimer G2 and tetramer G4) separated by sucrose density gradient centrifugation. In contrast, IC50 values for [3H]nicotine displacement (a measure of nicotinic cholinergic receptor binding) differed 1000-fold for THA (2 x 10(-5) M) and physostigmine (2 x 10(-2) M) and 100-fold for [3H]N-methylscopolamine displacement (a measure of muscarinic cholinergic receptor binding). Differences were also noted in the inhibition of carbachol stimulated polyphosphoinositide (PI) hydrolysis (a measure of muscarinic receptor induced second messenger activity) in isolated rat cortical miniprisms. It is suggested that variations in clinical efficacy of THA and physostigmine may be related less to their anticholinesterase properties and more to their interactions with other activities such as cholinergic receptors.
journal_name
Neurosci Lettjournal_title
Neuroscience lettersauthors
Perry EK,Smith CJ,Court JA,Bonham JR,Rodway M,Atack JRdoi
10.1016/0304-3940(88)90770-7subject
Has Abstractpub_date
1988-08-31 00:00:00pages
211-6issue
2eissn
0304-3940issn
1872-7972pii
0304-3940(88)90770-7journal_volume
91pub_type
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