Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to investigate whether cholinesterase (ChE) inhibitor exerts cardiovascular collapse through non-cholinergic mechanism in halothane-anesthetized rabbits. Physostigmine and N-methylcarbamate insecticides (BPMC = 2-sec-butylphenyl methylcarbamate and PHC = propoxur = 2-isopropoxyphenyl methylcarbamate) were employed as ChE inhibitors. Intravenous injection of physostigmine produced a dose-related pressor response a few minutes after the injection. In contrast, the injection of BPMC elicited a dose-related depressor response during the injection. PHC produced a slight depressor response during the injection followed by a dose-dependent pressor response. Norepinephrine (NE)-induced pressor response was inhibited by the ChE inhibitors with the same order and magnitude as the depressor response. ECG of physostigmine or PHC was characterized by an increase in QRS voltage and a sinus bradycardia, and that of BPMC by a decrease in QRS voltage. Atropine pretreatment inhibited the pressor response, the increase in QRS voltage and the sinus bradycardia, but not the depressor response and the decrease in QRS voltage. From these observations, it is suggested that the pressor response is ascribed to the cholinergic mechanism (acetylcholine accumulation through ChE inhibition), but the depressor response may result from a non-cholinergic mechanism. It is also suggested that the difference in the cardiovascular response is determined by a balance between cholinergic and non-cholinergic activity of each ChE inhibitor.
 ...
PMID:Cardiovascular collapse through non-cholinergic mechanism after intravenous injection of N-methylcarbamate insecticide in rabbits. 905 95

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.
 ...
PMID:The role of cholinergic and noncholinergic mechanisms in the cardiorespiratory failure produced by N-methylcarbamate cholinesterase inhibitors in rabbits. 1081 50