Abstract：
:The relation of the structure of 31 quaternary ammonium compounds (28 inhibitors; 3 substrate analogues) with their effects on the activity of acetylcholinesterase (EC 3.1.1.7; AChE) was studied. The compounds were structurally related to the natural substrate acetylcholine (ACh). All bear a trimethylammonium moiety as cationic head. The inhibitors include a variety of functional groups instead of an electrophilic ester group, making these substances suitable to probe the esteratic subsite. The inhibition constants and Km values were determined in kinetic experiments under steady state conditions (pH-stat method). Most of the substances acted as reversible, competitive inhibitors with KI in the range of 10(-6)-10(-3) M. The substrate analogues had Km values between (1.2-2.2) X 10(-4) M. The data allow the following main conclusions: (1) The quaternary trimethylammonium group of ACh is of high importance for substrate binding to AChE. It mediates association at the anionic site. (2) A poorer contribution to binding (two orders of magnitude lower) is attributable to the apolar methylene chain in ACh. It can be related to a hydrophobic interaction of the hydrocarbon chain at a region neighbouring the anionic site. (3) The ester group (both C = O and O) does not contribute to substrate binding. It is only responsible for reactivity.
journal_name
Eur J Pharmacoljournal_title
European journal of pharmacologyauthors
Thanei-Wyss P,Waser PGdoi
10.1016/0922-4106(89)90007-2subject
Has Abstractpub_date
1989-05-11 00:00:00pages
165-73issue
2eissn
0014-2999issn
1879-0712journal_volume
172pub_type
杂志文章abstract：:The distribution of the binding of [3H]GR65630 (0.2 nM) to putative 5-HT3 recognition sites in the brain of the common marmoset was assessed using autoradiography. Specific binding was heterogeneously distributed with the highest densities found in discrete nuclei of the lower medulla (nucleus tractus solitarii, dorsa...
journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/0014-2999(92)90609-8
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abstract：:Naloxone, a competitive antagonist of opioid receptors, and placebo (dextrose 5% in water (D5W) were administered on separate days to healthy normotensive (NT) male volunteers and to male patients with essential hypertension (HT). A single-blind, placebo-controlled, cross-over design was employed. Increasing doses of ...
journal_title：European journal of pharmacology
pub_type： 临床试验,杂志文章
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更新日期：1988-01-12 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2015.06.018
更新日期：2015-08-15 00:00:00
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journal_title：European journal of pharmacology
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更新日期：2008-12-03 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：1990-09-04 00:00:00
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journal_title：European journal of pharmacology
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
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更新日期：1994-06-13 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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更新日期：2002-12-13 00:00:00
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
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journal_title：European journal of pharmacology
pub_type： 杂志文章
doi：10.1016/j.ejphar.2013.12.014
更新日期：2014-02-05 00:00:00
