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

Characteristics of neuromuscular block produced by polymyxin B (PXB) were examined in 12 anesthetized cats, using sciatic nervetibialis anticus muscle preparations. The ED50 was 6.7 (+/- 1.4, SD) PXB base/kg body weight. The ED95 was 10.8 (+/- 2.4) mg/kg. Spontaneous recovery from 25 percent of control to 75 percent of control required 72 (+/- 16) minutes. During a 50 percent block, train-of-four twitches elicited at 2 Hz faded with a train-of-four ratio of 0.42 (+/- 0.13), but the tetanus did not fade. Edrophonium Cl, neostigmine methylsulfate, and pyridostigmine Br at sub-clinical dosages weakly antagonized the block but enhanced the block at anti-curare dosages. All 3 cholinesterase inhibitors were short acting, lasting 10 to 15 minutes, and noncumulative on repeated injection. The potency ratio was approximately 20:10:1 in the order of edrophonium, neostigmine, and pyridostigmine on a weight-for-weight basis. Calcium partially antagonized the block. The authors conclude that neuromuscular blocks produced by various antibiotics differ from each other and from that produced by other groups of neuromuscular blocking agents, including curare.
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PMID:Neuromuscular block by antibiotics: polymyxin B. 19 5

After discussion of the modern concepts of pathophysiology of ocular myasthenia the ocular symptoms such as ptosis and eye muscle palsies are discussed. As important diagnostic sign the Simpson lid fatigue test before and after application of Tensilon is described. For diagnosis of myasthenic eye muscle palsies electrooculography has a special significance especially in connection with the application of Edrophonium, which normalizes myasthenic hypometric saccades and transforms them even in hypermetric saccades. In doubtful cases of eye muscle palsies the electromyogram of the affected muscle in connection with the Edrophonium-test is extremely valuable. With regard to modern treatment apart from cholinesterase inhibitors (Pyridostigmine, Neostigmine) thymectomy, the application of corticosteroids, ACTH and especially also immune suppressive drugs (Imurel etc.) is discussed. Of great significance in ocular myasthenia is the local application of cholinesterase inhibitors like Eserine, Prostigmin or Phospholine Iodide.
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PMID:[Diagnosis and treatment of ocular myasthenia (author's transl)]. 20 42

Based on 60 of our own cases and on the medical literature the authors discuss the diagnostic, pathophysiological and therapeutic aspects of myasthenia gravis. Myasthenia is suspected in cases of motor weakness of changing intensity, diminishing by rest. The weak muscles are innervated by different peripheral nerves. At the beginning a weakness of upperlid-muscles, external eye muscles and bulbar muscles is particularly frequent. There is no sensory loss or other neurological symptoms. A transitory disappearance of motor weakness after an intravenous dose of Edrophonium (Tensilon) is a typical diagnostic sign. The effect is less evident with eye-muscle weakness. A typical appearance of potentials after repetitive stimulation of peripheral nerves as well as other characteristics in electrophysiological testing of muscles are of high diagnostic value. This allows differentiation from other types of muscle weakness. In the pathogenesis of myasthenia an autoimmune process related to a persistent thymus gland plays an important part. This leads to an ultrastructural change in the postsynaptic membrane of the muscle fibre. The postsynaptic membrane no longer reacts in a normal way to acetylcholine as a transmitter substance at the level of the motor endplate. Therefore the first step in the treatment of myasthenia consists of cholinesterase-inhibitors, specially Neostigmin (Prostigmin) and Pyridostigmin (Mestinon). Thymectomy is advised in all cases of myasthenia with the exception of the pure ocular form and of myasthenia in patients older than 60 years. The thymus gland is practically always persistent or hypertrophic in myasthenia. The suprasternal access is recommended. A thymoma should always be operated upon because of the danger of malignancy. In cases where thymectomy is not performed or not successful and if cholinesterase-inhibitors are not sufficiently efficient, treatment with corticosteroids or ACTH is recommended.
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PMID:[Pseudoparalytic myasthenia gravis. Diagnostic and therapeutic aspects in 60 separate cases]. 98 76

The effects of pharmacologic modulation of vagal activity on ischemic ventricular tachycardia were evaluated in 21 conscious dogs after permanent left anterior descending coronary artery (LAD) occlusion. Studies were done on spontaneous ventricular tachycardia (cycle length 383 +/- 100 msec, n = 21), 24 to 72 hours after LAD occlusion, and on inducible sustained monomorphic ventricular tachycardia (cycle length 251 +/- 30 msec, n = 6), 4 to 7 days after LAD occlusion. Edrophonium (1 mg/kg intravenously), a cholinesterase inhibitor, and methacholine (0.1 to 1 mg intravenously), a muscarinic agonist, had no significant effect on the rate or QRS morphology of either type of tachycardia, despite severe slowing of the sinoatrial rate. Similarly, atropine (up to 60 micrograms/kg intravenously) had no effect on the rate and QRS morphology of either type of tachycardia. In an attempt to enhance myocardial drug delivery to the ischemic and infarcted left ventricle, edrophonium (1 mg/kg) and methacholine (0.1 to 0.2 mg) were injected retrogradely through the great cardiac vein. This did not impart any significant therapeutic advantage over the systemic intravenous route. Sympathetic beta blockade did not affect the therapeutic outcome (n = 5) with either edrophonium or methacholine. It is concluded that direct or indirect enhancement of cardiac vagal activity has no effect on ischemic ventricular tachycardia in this model of subacute myocardial infarction. The lack of efficacy appears to be independent of myocardial drug delivery to ischemic ventricular site(s) and background sympathetic activity. Such a lack of efficacy may be caused by ischemia-mediated degeneration of vagal nerve terminals, by altered responsiveness of muscarinic receptors at infarcted arrhythmogenic myocardial sites, or both.
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PMID:The role of enhanced vagal activity on ischemic ventricular tachycardia: pharmacologic basis of inefficiency. 167 35

1. The influences of enzyme treatments (trypsin and collagenase) on responses to perfused acetylcholine were examined on physically isolated single Aplysia neurons, using the voltage-clamp, internal perfusion, and rapid external perfusion technique. 2. During treatment with trypsin (0.025 to 0.1%) for 10 to 30 min at room temperature (22 to 25 degrees C), the peak amplitude of the Na current induced by acetylcholine increased in a time- and dose-dependent manner, and the decay in the continued presence of acetylcholine was slowed. This effect of trypsin treatment was irreversible after washing for 60 min without enzyme. 3. Edrophonium, a cholinesterase inhibitor, has previously been shown to augment the Na acetylcholine response in this preparation by inhibition of acetylcholinesterase. After treatment of the neuron with trypsin, the augmentation after edrophonium was abolished. Furthermore, in the presence of edrophonium, trypsin also failed to increase the response. The dose-response curve for acetylcholine after treatment of trypsin was similar to that in the presence of edrophonium. These results suggest that the modification of the current response by trypsin is a result of removal of cholinesterase activity from the membrane. 4. In contrast to the effects of trypsin, collagenase (0.03 to 0.1%) for 10 to 60 min did not change the current amplitude of the acetylcholine response. However, collagenase treatment did alter the kinetics of the acetylcholine response in a dose-dependent manner, in that the rate of decay was accelerated. A similar acceleration was seen in the acetylcholine responses on other neurons which were due to Cl or K currents, suggesting that the effect was independent on the type of channel. This effect of collagenase was reversible after 30 to 60 min of washing of the neuron. 5. In the presence of edrophonium or after the treatment with trypsin, collagenase still accelerated the current kinetics of the acetylcholine response, indicating that cholinesterase activity is not related to this effect. Furthermore, heated collagenase (presumably inactivated) had a similar action, suggesting that the enzymatic activity of collagenase is not related to the modification of the response. 6. These results suggest that Aplysia acetylcholinesterase is sensitive to trypsin but not to collagenase. However, the preparation of a collagenase used in these studies contains some factor which alters the response to acetylcholine, but this effect is reversible and unrelated to enzymatic activity.
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PMID:Influences of trypsin and collagenase on acetylcholine responses of physically isolated single neurons of Aplysia californica. 216 51

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P less than 0.05), despite Day 7 cholinesterase activity that was 16% of pre-trichlorfon values. For atracurium Injections 1 and 2-5, 85 and 43 micrograms/kg of atracurium, respectively, were required to produce a 95-99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2-5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre-atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane-anesthetized horses. 281 Apr 76

Antibodies against acetylcholinesterase were found in the serum of a patient presenting dyspnea, generalized muscle paresis, diminished tendon reflexes, and fasciculations. Electrodiagnostic studies showed a decremental response, an incomplete interference pattern, and reduced motor nerve conduction velocity. Edrophonium administration resulted in extreme cholinergic crisis. Biopsies displayed muscle atrophy and nervous tissue degeneration. Recurrent acute respiratory failure ended in death. The patient's serum pseudocholinesterase and red blood cells acetylcholinesterase levels were generally very low, with periodical fluctuations. Minute quantities of the patient's serum inhibited the activity of cholinesterases from normal human serum and from various fetal tissues. Enzyme inhibition was abolished following preadsorption of the serum immunoglobulins with goat antihuman Fab, and radioiodinated acetylcholinesterase from human erythrocytes was precipitated by the patient's serum, confirming that anticholinesterase antibodies were present. Acetylcholinesterase extracted from fetal striated muscle with detergent and salt was inhibited to a larger extent than the enzymes similarly prepared from other fetal tissues and more efficiently than buffer-soluble muscle enzyme. These findings suggest that the patient's serum contained antibodies which interacted preferentially with the membrane-associated forms of muscle acetylcholinesterase and indicate that autoantibodies against acetylcholinesterase could play a role in the pathogenesis of the disease.
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PMID:Antibodies against acetylcholinesterase and low levels of cholinesterases in a patient with an atypical neuromuscular disorder. 339 Sep 68

The cholinergic agonists acetylcholine (ACh), carbamylcholine and methacholine were found to be equieffective in reducing the force of left atrial contraction, but to differ in their ability to shorten the action potential duration. The irreversible cholinesterase inhibitor soman had no effect on the actions of the non-hydrolyzable agonist carbamylcholine, but potentiated the actions of ACh. The reversible inhibitor edrophonium both potentiated and antagonized the effects of ACh. It antagonized the effects of carbamylcholine and after atrial cholinesterase was inhibited with soman it also antagonized the effects of ACh. Its anticholinesterase action and inhibitory action at the muscarinic receptor were confirmed in separate studies. Edrophonium is approximately 12 times more potent as an anticholinesterase than it is in blocking the muscarinic receptor. However, some actions of edrophonium cannot be explained in the context of its anticholinergic and antiesterase actions. Thus it increases the force of atrial contraction and antagonizes the negative inotropy due to soman. An inhibitory effect on an outward K+ current may be involved. The difference in the ability of the three cholinergic agonists to shorten the action potential may also be related to differences in efficacy at this K+ channel.
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PMID:Modification of the effects of muscarinic agonists by reversible and irreversible anticholinesterase compounds in the guinea pig atrium. 351 25

Ocular myasthenia is a special form of general myasthenia gravis characterized by unilateral or bilateral ptosis and eye muscle pareses of distinct variability, depending on the time of day and the state of fatigue of the patient. Most important for diagnosis is the Tensilon test, which can, however, produce negative results. In such cases a combination of the Tensilon test with electromyography is indispensable. In ocular myasthenia there is not always an increase in the antibody titer against acetylcholine receptors in the blood. The treatment of ocular myasthenia is based on the application of cholinesterase inhibitors. The drug of choice is Mestinon; however, the reaction of the eye muscles to this drug is often unsatisfactory. Local application of cholinesterase inhibitors in the form of Eserine, Prostigmin etc. is an additional important therapy. Also in ocular myasthenia the modern treatment with Cortisone (alternate-day therapy with 100 mg Prednisone every second day) has proved very useful. Another possible method of interfering with the immunological systems of myasthenia is immunosuppression with Azathioprin or Cyclophosphamide. The pathognomonic significance of the thymus in the autoimmune process of myasthenia gravis is demonstrated by the good results obtained by thymectomy, which can also be performed successfully in ocular myasthenia, not only in young patients in whom the condition is severe, but also in older patients in whom it is chronic. Often, the therapeutic measures mentioned have to be tested one after another or in combination in order to achieve an optimal therapeutic effect.
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PMID:[Ocular myasthenia]. 399 98

1. Contractions of the isolated taenia of the guinea-pig caecum produced by acetylcholine and TMA were examined in the presence of various antagonists and anticholinesterases.2. Hemicholinium-3 (HC-3) (50-400 mug/ml) inhibited contractions or relaxations produced by TMA but not contractions produced by acetylcholine. The inhibition was rapid in onset and readily reversible. Contractions produced by transmural stimulation were unaffected by HC-3 but responses produced by nicotine were inhibited.3. Low concentrations of hyoscine and benzhexol inhibited responses to acetylcholine to a greater extent than those to TMA.4. Morphine, raised concentrations of Mg(++) or reduced concentrations of Ca(++) inhibited contractions produced by TMA and by acetylcholine to a similar extent.5. Edrophonium, in concentrations which preferentially inhibit acetylcholinesterase, increased contractions produced by acetylcholine and converted responses to nicotine or transmural stimulation into contractions or biphasic responses with a marked contraction phase but did not increase contractions produced by TMA.6. Iso-OMPA, in concentrations which preferentially inhibit butyrylcholinesterase, had no effect on responses to acetylcholine, nicotine, transmural stimulation or TMA.7. HC-3 inhibited contractions produced by TMA in the presence of anticholinesterases but had little effect on contractions produced by acetylcholine.8. These results suggest that TMA produces contractions by acting directly on receptors of the smooth muscle. An analysis of possible reasons for HC-3 (in the concentrations used) acting as an antagonist of TMA but not of acetylcholine indicates that the findings do not necessarily contradict the interpretation that both agonists act on the same receptor.
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PMID:Differentiation between the actions of acetylcholine and tetramethylammonium on the isolated taenia of the guinea-pig caecum by hemicholinium-3. 432 8


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