Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiarrhythmic drug bretylium tosylate competitively inhibits acetylcholinesterase activity. The Ki values for the inhibition of the purified enzyme (from electric eel), and acetylcholinesterase activity of crude rat ventricular and cortical homogenates were 6 X 10(-5), 3 X 10(-5), and 8 X 10(-5) M respectively. These values are close to the concentrations of the drug known to induce norepinephrine release from cardiac adrenergic presynaptic vesicles. It is suggested that inhibition of acetylcholinesterase activity by bretylium induces norepinephrine release through the effect of accumulated acetylcholine on nicotinic receptors in adrenergic nerve terminals.
J Cardiovasc Pharmacol
PMID:Competitive inhibition of acetylcholinesterase by bretylium: possible mechanism for its induction of norepinephrine release. 241 89

The influence of digoxin on the autonomic nervous system was studied in rats by examining its effects on the levels of acetylcholine (Ach), a parasympathetic marker, and norepinephrine (NE), a sympathetic marker, in the rat myocardium. Ach and NE were measured by high performance liquid chromatography with electrochemical detection (HPLC-ECD). Digoxin was injected subcutaneously every day for 4 weeks. The administration of 0.35, 0.75, and 2.5 mg/kg of digoxin reduced Ach concentrations in the right atrium to about 80-90% of the control value. However, there was no change in the activity of choline acetyltransferase (ChAT) or acetylcholinesterase (AchE), or in the concentration of choline (Ch). Injection of 0.1 mg/kg of digoxin had no significant effect on Ach concentration. When 0.75 and 2.5 mg/kg of digoxin were injected, there was a significant increase in NE concentration in the right atrium. Neither 0.1 nor 0.35 mg/kg caused any changes. Digoxin (0.75 and 2.5 mg/kg) increased heart rate to about 110% of the control values. Thus, high doses of digoxin increase the NE concentration but decrease the Ach concentration in the rat heart, and these changes might be related to functional changes in the autonomic nervous system.
J Cardiovasc Pharmacol 1989 May
PMID:Effects of digoxin on acetylcholine and norepinephrine concentrations in rat myocardium. 247 17

A previously unrecognized beneficial drug interaction is described. Without affecting the antiarrhythmic properties of disopyramide, a sustained-release form of pyridostigmine (a cholinesterase inhibitor) was shown to prevent completely anticholinergic side effects in a study population (17 patients), whereas side effects occurred in 26 of 89 patients (29%) in a control group (p less than 0.025). Pyridostigmine also diminished or abolished disopyramide-induced anticholinergic side effects in each of 10 patients in whom they were already present. Pyridostigmine allowed an increase in tolerated disopyramide blood levels (4.53 +/- 1.59 micrograms/ml versus 3.85 +/- 1.78 micrograms/ml) and a significant increase in disopyramide dosages (224 +/- 68 mg versus 188 +/- 68 mg every 6 h) (p less than 0.02). No patients suffered side effects from pyridostigmine. These data suggest that pyridostigmine can be used to prevent as well as to treat the anticholinergic side effects of disopyramide. The usefulness of disopyramide has previously been limited by these anticholinergic side effects. Further investigation is in progress to determine what role pyridostigmine can play in making disopyramide therapy available to patients who otherwise could not benefit from its use.
J Cardiovasc Pharmacol
PMID:Disopyramide-pyridostigmine: report of a beneficial drug interaction. 258 Jan 28

Intravenous injection of the cholinesterase inhibitor physostigimine evoked a hypertensive response in the unanesthetized 12- to 14-week-old spontaneously hypertensive rat (SHR). These responses were greatly enhanced in magnitude when compared to similar injections in normotensive Wistar-Kyoto (WKY) control rats. Stimulation of autonomic ganglia with dimethylphenylpiperazinium (DMPP) also evoked a pressor response in SHR; however, the magnitude of these responses was not different from those obtained in WKY. In unanesthetized, freely moving SHR, the intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) to block the synthesis of brain acetylcholine (ACh) produced a marked hypotensive response. No reduction in arterial pressure was observed following similar injections of HC-3 in WKY. The decline in arterial pressure following icv HC-3 was correlated with the initial decline in brain ACh levels, particularly in the hypothalamus. These results indicate that enhanced sympathetic nerve activity and the resultant hypertensive state present in young SHR is dependent on increased central cholinergic activity.
J Cardiovasc Pharmacol
PMID:Role of central cholinergic neurons in experimental hypertension. 615 33

Twenty cases of failing transcervical thymectomy are reported. They were selected for transsternal re-exploration from a series of 95 patients who had previously undergone transcervical thymectomy because of myasthenia gravis (MG). A specific method for pre-operative detection of remnants of the non-tumorous thymic gland is lacking, but the applied clinical selection criteria were so far reliable: generalized, disabling, fluctuating MG despite cholinesterase inhibitor and/or immunosuppressive treatment, and no or inconsistent improvement after transcervical thymectomy. At transsternal re-exploration the commonest findings were intact lower thymic lobes with persistent venous drainage into the brachiocephalic vein. Presence of thymic tissue was histologically confirmed in all the excised specimens (weight range 10-60, mean 23 g), and the examination showed thymic hyperplasia in 18 cases, fatty involution of the gland in two, and a lympho-epithelial thymoma in one case. The re-operation was followed by objectively registrable improvement in all but one of the 20 patients during observation periods of 8-75 (mean 21) months. There was statistically significant reduction in disability scores (means 8.2-4.9) and in need for anticholinesterase medication (to 67% of pretreatment dose). Immunosuppression became unnecessary in 6 of 11 patients and could be reduced in 4 patients. The incidence of failure in transcervical thymectomy was alarmingly high (27%), and more re-operations are anticipated. Since the transcervical approach involves a high risk of incomplete thymectomy, its use should be abandoned. However, in most of the patients with re-operation, subsequent progress has been sufficiently promising for advocacy of sternotomy whenever the clinical criteria of failure are fulfilled.
Scand J Thorac Cardiovasc Surg 1984
PMID:Failing transcervical thymectomy in myasthenia gravis. An evaluation of transsternal re-exploration. 652 69

Quinacrine-fluorescent nerve fibres and nerve cell bodies are described in the right and left atria of the guinea-pig and rabbit. The nerve cells (20 to 35 micrometers in diameter) are found predominantly in the right atrium in both species. The nerve fibres are varicose and innervate both the muscle and many blood vessels. The quinacrine fluorescent neural structures are unaffected by chemical sympathectomy with 6-hydroxydopamine. The distribution of quinacrine-positive nerve fibres and cell bodies are compared to the distribution of adrenergic and acetylcholinesterase-positive nerves in the atrium of both species. Quinacrine fluorescence appears to be selective for non-adrenergic, non-cholinergic nerves and the possibility that it is binding to high contents of ATP discussed.
Cardiovasc Res 1982 Jul
PMID:Fluorescent histochemical localisation of quinacrine-positive neurones in the guinea-pig and rabbit atrium. 712 52

Heart failure is associated with attenuation of parasympathetic nervous function and enhanced renin-angiotensin activity. We tested whether there was a dysfunction in the efferent cholinergic neurotransmission in the heart of rats with chronic myocardial infarction (MI) and the potential role of angiotensin II (Ang II) receptors in such changes. Rats with MI and sham-operation were anesthetized, and heart rate (HR) reduction in response to vagal nerve stimulation was measured before and after losartan administration (10 mg/kg, i.v.) in the presence or absence of physostigmine to inhibit acetylcholinesterase. Infarcted rats had an average infarct size (IS) of 38% of the left ventricle (LV), depressed LV dP/dtmax, elevated LVEDP, and cardiac hypertrophy. Nerve stimulation (1-16 Hz) reduced HR in a frequency-dependent manner. The bradycardiac responses were significantly attenuated in infarcted versus control rats (p < 0.01), indicating an impaired efferent vagal tone. In contrast, the bradycardic response to exogenous acetylcholine was similar in both groups, implying an unchanged muscarinic receptor responsiveness in hearts with MI. HR response to nerve stimulation was potentiated by losartan in infarcted rats by 21 +/- 4 versus 4 +/- 2 beats/min (p < 0.01) but was unaffected in control rats. This effect of losartan was inversely related to the extent of attenuation of vagally mediated HR reduction. IS was correlated with both the extent of attenuation in vagally mediated bradycardia and the effect of losartan. In conclusion, the efferent vagal control of HR is attenuated in rats with MI and heart failure. This attenuation may be partly due to a presynaptic inhibition of acetylcholine release through the tonic activation, by Ang II, of neuronal AT1 receptors.
J Cardiovasc Pharmacol 1998 Jun
PMID:Depression of efferent parasympathetic control of heart rate in rats with myocardial infarction: effect of losartan. 964 80

We have studied the effects of various angiotensin-converting enzyme (ACE) inhibitors on intraocular pressure (IOP) of rabbits with experimentally induced ocular hypertension and their mechanism of action. Acute ocular hypertension was induced by infusion of 5% glucose (15 ml/kg) through marginal ear vein, whereas chronic glaucoma was induced by injection of alpha-chymotrypsin into the posterior chamber of the eye. IOP was measured by tonometer. All ACE inhibitors were instilled topically in the eye in a sterile solution. The effect of ACE inhibitors also was studied on serum cholinesterase (true and pseudo) and the enzyme ACE in vitro. Enalaprilat, ramiprilat, and fosinopril produced a time-dependent decrease of IOP in both acute and chronic models of ocular hypertension in rabbits. The decrease in IOP was observed for >4 h, and the extent of decrease was comparable to that with both pilocarpine and betaxolol. Prodrugs enalapril and ramipril failed to produced any change in IOP. Losartan also produced a significant decrease in IOP in the chronic model of ocular hypertension in rabbits. All the three ACE inhibitors were found to inhibit ACE activity in aqueous humor. The enzyme cholinesterase was found to be inhibited by enalaprilat, ramiprilat, and fosinopril. However, atropine did not alter the IOP-lowering effect of enalaprilat in rabbits. Indomethacin pretreatment produced slight but significant inhibition of the IOP-lowering effect of enalaprilat in rabbits. Our data suggest that ACE inhibitors enalaprilat, ramiprilat, and fosinopril produce a significant ocular hypotensive effect in acute and chronic models of ocular hypertension in rabbits. Inhibition of ACE in aqueous humor, and in ocular tissues, resulting in reduced angiotensin II formation, could be one of the major mechanisms responsible for the IOP reduction by ACE inhibitors in rabbits.
J Cardiovasc Pharmacol 2000 Aug
PMID:Oculohypotensive effect of angiotensin-converting enzyme inhibitors in acute and chronic models of glaucoma. 1094 57

An acetylcholinesterase inhibitor (donepezil hydrochloride) has recently been used for the treatment of senile dementia of Alzheimer type. The effect of this acetylcholinesterase inhibitor on the autonomic nervous control of the heart was investigated in 17 patients with senile dementia of Alzheimer type. Donepezil administration did not change the plasma concentration of norepinephrine or epinephrine. Twenty-four hour electrocardiogram monitoring was performed, and heart rate variability before and 6 weeks after treatment with donepezil (5 mg per orally) was determined. The heart rate averaged over 24 h was reduced slightly from 74.1 +/- 2.7 beats/min before treatment to 71.1 +/- 2.3 beats/min after treatment. Low (0.04-0.15 Hz) and high (0.15-0.40 Hz) frequency components were reduced significantly with treatment. Ultralow (0.0001-0.003 Hz) and very low (0.003-0.04 Hz) frequency components were not affected. The reduction in the high frequency (41.9 +/- 7.4%) component was greater (p < 0.03) than the reduction in the low frequency (18.6 +/- 10.7%) component. It therefore appears that acetylcholinesterase inhibitor reduces the 1-30 s modulation of heart rate variability but that it has no influence on the much longer 1 min-1 h fluctuation.
J Cardiovasc Pharmacol 2003 Jan
PMID:Acetylcholinesterase inhibitor (donepezil hydrochloride) reduces heart rate variability. 1268

The predictive factors of surgical outcome were evaluated in compromised patients following cardiovascular surgery. Of 608 patients undergoing cardiovascular surgery between 1991 and 1999, 55 stayed in the intensive care unit for 2 weeks or longer. The mean age of these 55 patients was 56 years. There were 35 survivors and 20 nonsurvivors. Postoperative respiratory failure and gastrointestinal complications were significantly more frequent in those who died. The survival rate was significantly higher in patients who had enteral feeding compared to those who did not (88% versus 43%). Serum cholinesterase and total cholesterol concentrations were higher in the survivors. It was concluded that postoperative respiratory and gastrointestinal conditions influenced the surgical outcome, and serum cholinesterase and total cholesterol concentrations were valuable predictors of survival.
Asian Cardiovasc Thorac Ann 2004 Sep
PMID:What influences the results in critical patients after cardiovascular surgery? 1535 66


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