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The role of cholinergic and noncholinergic mechanisms in the cardiorespiratory failure produced by N-methylcarbamate cholinesterase inhibitors in rabbits.

Abstract：

:We investigated the relative contribution of several cardiorespiratory components to acute lethality produced by N-methylcarbamate cholinesterase (ChE) inhibitors physostigmine, 2-sec-butylphenyl methylcarbamate (BPMC), and 2-isopropoxyphenyl methylcarbamate (PHC) in halothane-anesthetized rabbits. Intravenous injection of these compounds produced dose-dependent pressor and/or depressor responses related to each compound. A lethal dose of physostigmine resulted in cardiovascular collapse after a pressor response. That of PHC produced cardiovascular collapse after biphasic effects on blood pressure, a transient decrease followed by an increase. Unlike these compounds, BPMC elicited a rapidly developing depressor response followed by cardiovascular collapse. Artificial ventilation prevented cardiovascular collapse and lethal actions to physostigmine and PHC, but not BPMC. A degree of acute lethality to physostigmine and PHC depended on their anti-ChE activity, whereas BPMC exhibited a low degree of lethality relative to its anti-ChE activity. While the pressor response to physostigmine and PHC was ascribed to an atropine-sensitive increase in cardiac contractility, the depressor response to PHC and BPMC was attributed to an atropine-insensitive decrease in cardiac contractility and/or vascular resistance. Similar to the order for eliciting the depressor response in vivo, all three compounds inhibited contraction of the isolated cardiac and aortic smooth muscles with the order of their inhibition in terms of anti-ChE activity, i.e., BPMC > PHC > physostigmine. Thus, the primary cause of death with physostigmine and PHC is respiratory arrest subsequent to ChE inhibition, whereas BPMC exhibiting the low degree of lethality causes cardiovascular collapse mediated through direct inhibitory effects on cardiac and vascular smooth muscle contraction.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Futagawa H,Kakinuma Y,Takahashi H

doi

10.1006/taap.2000.8924

subject

Has Abstract

pub_date

2000-05-15 00:00:00

pages

27-36

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(00)98924-5

journal_volume

165

pub_type

杂志文章

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The role of cholinergic and noncholinergic mechanisms in the cardiorespiratory failure produced by N-methylcarbamate cholinesterase inhibitors in rabbits.