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At least 19 recordsLinked to original sources
PubMed1989

Train-of-four ratio after antagonism of atracurium with edrophonium: influence of different priming doses of edrophonium.

This study was designed to investigate the effect of different priming doses of edrophonium on the relationship between the the recovery of the first twitch of the train-of-four (T1) and train-of-four (TOF) ratio. This relationship was studied after the administration of the full dose of the antagonist in all groups. Edrophonium 1.0 mg.kg-1 was administered either in a single bolus dose (Group I, controls) or in an initial dose of 0.05, 0.1, 0.15 or 0.2 mg.kg-1 followed one minute later by the remainder of the 1.0 mg.kg-1 dose in Groups II to V. Reversal was attempted at the ten per cent spontaneous recovery of twitch height (T1) from atracurium-induced neuromuscular blockade. Of all the groups studied, Group V had a significantly greater recovery in the TOF ratio at any given T1 value. When first twitch tension (T1) had recovered to 100 per cent of the control, it was found for the same tension that the TOF ratio was greater in Group V, being 0.75 compared to 0.63, 0.65, 0.65 and 0.64 in Groups I to IV respectively. The implication is that this differential ability to reverse fade (or prejunctional activity) may be involved in the acceleration of recovery.

Adult↗
PubMed1995

Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. RESULTS: With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Adolescent↗
PubMed1995

The maximum depth of an atracurium neuromuscular block antagonized by edrophonium to effect adequate recovery.

BACKGROUND: The inability of edrophonium to rapidly reverse a deep nondepolarizing neuromuscular block may be due to inadequate dosage or a ceiling effect to antagonism of neuromuscular block by edrophonium. A ceiling effect means that only a certain level of neuromuscular block could be antagonized by edrophonium. Neuromuscular block greater than this could not be completely antagonized irrespective of the dose of edrophonium administered. The purpose of this study was to determine whether a ceiling effect occurred for antagonism of an atracurium-induced neuromuscular block by edrophonium and, if so, the maximum level of block that could be antagonized by edrophonium. METHODS: In 30 adult patients, atracurium was administered to maintain a constant neuromuscular block. The level of block varied between patients. Evoked adductor pollicis twitch tension was monitored. Incremental doses of edrophonium were administered while the infusion of atracurium continued. Increments were given until adequate recovery occurred, as defined by a train-of-four (TOF) ratio > or = 70%, or until no further antagonism of the block could be achieved. The probability of being able to effect adequate recovery by antagonism with edrophonium was determined using a logistic regression model. Cumulative dose-response curves were constructed using the logit transformation of the neuromuscular effect versus the logarithm of the cumulative dose of edrophonium. RESULTS: In 14 patients with a block of 25-77% depression of the first twitch response, antagonism by edrophonium to a TOF ratio > or = 70% was possible, whereas in 16 patients with a 60-92% depression of T1, a TOF ratio > or = 70% was not achievable, indicating that a ceiling effect for antagonism by edrophonium occurred. A block of 67 +/- 3% (mean +/- SE) had a 50% probability of adequate antagonism. In patients in whom block was antagonized to a TOF ratio < 70%, 95% of the peak antagonistic effect occurred with an edrophonium dose of 0.8 +/- 0.33 mg.kg-1 (mean +/- SD). CONCLUSIONS: There is a maximum level of neuromuscular block that can be antagonized by edrophonium to effect adequate recovery. The level corresponds approximately to the reappearance of the fourth response to TOF stimulation. It is probably safest to wait until this level of block occurs before edrophonium is given for reversal. Earlier administration will not hasten recovery.

Aged↗
PubMed2001

Interaction of edrophonium with muscarinic acetylcholine M2 and M3 receptors.

BACKGROUND: It has been reported that edrophonium can antagonize the negative chronotropic effect of carbachol. This study was undertaken to evaluate in detail the interaction of edrophonium with muscarinic Mz and M3 receptors. METHODS: A functional study was conducted to evaluate the effects of edrophonium on the concentration-response curves for the negative chronotropic effect and the bronchoconstricting effect of carbachol in spontaneously beating right atria and tracheas of guinea pigs. An electrophysiologic study was conducted to compare the effects of edrophonium on carbachol-, guanosine triphosphate (GTP)gama S-, and adenosine-induced outward K+ currents in guinea pig atrial cells by whole cell voltage clamp technique. A radioligand binding study was conducted to examine the effects of edrophonium on specific [3HIN-methylscopolamine (NMS) binding to guinea pig atrial (M2) and submandibular gland (M3) membrane preparations, and on atropine-induced dissociation of [3H]NMS. RESULTS: Edrophonium shifted rightward the concentration-response curves for the negative chronotropic and bronchoconstricting effects of carbachol in a competitive manner. The pA2 values for cardiac and tracheal muscarinic receptors were 4.61 and 4.03, respectively. Edrophonium abolished the carbachol-induced outward current without affecting the GTPgamma S- and adenosine-induced currents in the atrial cells. Edrophonium inhibited [3H]NMS binding to M2 and M3 receptors in a concentration-dependent manner. The pseudo-Hill coefficient values and apparent dissociation constants of edrophonium for M2 and M3 receptors were 1.02 and 1.07 and 21 and 34 microM, respectively. Edrophonium also changed dissociation constant values of [3H]NMS without affecting its maximum binding capacities. CONCLUSION: Edrophonium binds to muscarinic M2 and M3 receptors nonselectively, and acts as a competitive antagonist.

Animals↗
PubMed1992

The edrophonium-Hess screen test in the diagnosis of ocular myasthenia gravis.

The interpretation of the edrophonium (Tensilon) test in the diagnosis of acquired strabismus caused by myasthenia gravis has been problematic because of poorly defined endpoints and unknown sensitivity and specificity. We evaluated the endpoint criteria, dynamics, sensitivity, and specificity of binocular alignment in response to edrophonium by using the Hess screen test in ten normal control subjects, 12 nonmyasthenic patients with acquired strabismus, and in ten patients with acquired strabismus caused by ocular myasthenia gravis. A positive response to the edrophonium-Hess screen test was defined as a 50% or greater reduction in the strabismic deviation at the fixation point associated with maximum deviation within one minute of edrophonium infusion. All myasthenic patients had a 50% or greater reduction in the initial deviation within one minute of edrophonium infusion. Myasthenic patients had a statistically significant reduction in the average deviation up to 150 seconds after edrophonium infusion (P < .05 for all time periods). In contrast, with or without edrophonium infusion, control subjects had a purely horizontal fluctuation in binocular alignment of less than or equal to 2 degrees for the entire four-minute period after edrophonium infusion. None of the 12 nonmyasthenic patients tested positive to the edrophonium-Hess screen test. According to the criterion of positive response as was defined in this study, the test had a high sensitivity and specificity in this sample. These results suggest that clearly defined endpoint criteria make the edrophonium-Hess screen test a sensitive and specific quantitative study for the diagnosis of acquired strabismus caused by myasthenia gravis.

Adult↗
PubMed1986

Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions.

The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Atracurium↗
PubMed1991

Edrophonium priming alters the course of neuromuscular recovery from a pipecuronium neuromuscular blockade.

This study was designed to investigate the effect of divided administration of edrophonium on the course of neuromuscular recovery from a pipecuronium neuromuscular blockade. During thiopentone-nitrous oxide-halothane anaesthesia 48 patients were given pipecuronium 70 micrograms.kg-1. Patients were randomly assigned to one of four groups (n = 12 in each) to receive either edrophonium 1 mg.kg-1 (Groups I and II) or edrophonium 0.75 mg.kg-1 (Groups III and IV). In Groups I and III (single-dose groups), edrophonium was administered as a single bolus dose. In Groups II and IV (divided-dose groups) edrophonium was administered as an initial dose of 0.25 mg.kg-1 followed three minutes later by either 0.75 or 0.50 mg.kg-1 respectively. Reversal was attempted at 20% spontaneous recovery of twitch height. Administration of edrophonium in divided doses (Groups II and IV) accelerated the reversal of the pipecuronium neuromuscular blockade. At ten minutes post-reversal, train-of-four (TOF) ratio recovery reached 0.75 or more in 12 (100%) and in ten (83%) patients in Groups II and IV respectively. Similarly, times to attain a TOF of 0.75 (SEM) were shorter in the divided-dose groups than in the single-dose groups (P less than 0.05), being 354.5 (38.7) and 398.3 (49.1) sec in Groups II and IV vs 705.4 (66.6) and 651.2 (54.3) sec in Groups I and III respectively. Time was counted from the first administration of edrophonium. It is concluded that administration of edrophonium in divided doses produced a faster reversal of residual pipecuronium-induced neuromuscular blockade than single bolus administration. Also, administration in divided doses reduced the requirements of edrophonium needed for reversal of pipecuronium neuromuscular blockade.

Adult↗
PubMed1998

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission.

PURPOSE: To evaluate the effect of edrophonium on synaptic transmission in the superior cervical ganglion. METHODS: In anaesthetized rats the effect of edrophonium on synaptic transmission was studied in vitro by testing whether it blocks the compound action potential recorded from postganglionic fibres evoked by stimulation of preganglionic axons. The superior cervical ganglion was excised and the cervical sympathetic trunk and internal carotid nerve were used for stimulating and recording, respectively. Drugs superfused included edrophonium (0.1-500 microM), neostigmine (0.1-10 microM), and muscarinic M1 and M2 antagonists pirenzepine and AFDX-116 (200 nM-10 microM), respectively. To evaluate a presynaptic action, the effect of edrophonium on basal and high-K+ (35 mM) evoked release of [3H]ACh from the superior cervical ganglion was studied in vitro. To evaluate a postsynaptic action, edrophonium's effect on postganglionic nerve discharge in response to arterial injection of ACh (100 micrograms) into the superior cervical ganglion was determined in vivo. RESULTS: Edrophonium (10-500 microM) decreased the compound action potential amplitude (ED50 163.5 microM). A decrease was not produced by neostigmine, nor was it reversed by pirenzepine or AFDX-116. Edrophonium blocked postganglionic cell firing in response to exogenously administered ACh. Although edrophonium did not affect basal or high-K+ evoked ACh release, when the evoked increase was calculated as a multiple of the basal release, it caused approximately a 30% (P < 0.005) reduction. CONCLUSIONS: Edrophonium blocks ganglionic cholinergic transmission postsynaptically and, possibly, presynaptically. The mechanism(s) by which this occurs does not appear to involve inhibition of cholinesterase, or activation of M1 or M2 receptor subtypes.

Acetylcholinesterase↗
PubMed2000

The complication rate of edrophonium testing for suspected myasthenia gravis.

BACKGROUND: The incidence of life-threatening complications from edrophonium chloride (Tensilon) testing for suspected myasthenia gravis is thought to be extremely low. We carried out a survey to determine the rate of serious complications from such testing. METHODS: In April 1998, 357 physicians listed in the 1998 roster of the North American Neuro-ophthalmology Society were mailed a questionnaire for anonymous completion. Questions asked included the number of years the clinician had practised neuro-ophthalmology, the estimated number of edrophonium tests performed since completion of training, the number and nature of major complications from edrophonium, and whether the clinician preferred the sleep test or ice test to edrophonium testing. RESULTS: The response rate was 56% (199/357). Of the 199 respondents, 105 (53%) had practised neuro-ophthalmology for at least 10 years. The group estimated that they had performed at least 23,111 edrophonium tests, of which 37 (0.16%) were associated with a serious complication, mostly attributed to brady-arrythmias and syncope. Respiratory failure, seizure, severe vomiting and transient ischemic attack were also reported. Thirty-one respondents (16%) preferred the sleep test or ice test to the edrophonium test; one-third of this group reported a serious complication with edrophonium. INTERPRETATION: The rate of significant complications of edrophonium testing is low, but the complications can be potentially life threatening. Clinicians should know the nature and incidence of these complications when obtaining informed consent for edrophonium testing.

Cholinesterase Inhibitors↗
PubMed1982

Some actions of Org NC 45 and of edrophonium in the anaesthetized cat and in man.

Some actions of the muscle relaxant drug Org NC 45 on the tibialis anterior muscle of cats under barbiturate-chloralose anaesthesia have been studied. Its effects were characteristic of a neuromuscular blocking agent that acts predominantly, although not necessarily exclusively, by blocking postjunctional cholinoceptors. It was confirmed that one of the important features of the action of Org NC 45 is that, despite its high potency, its offset of action is unusually rapid. The pronounced antagonism of the block following an interposed tetanus suggested that Org NC 45 is more easily displaced from the endplate cholinoceptors than are tubocurarine or pancuronium, and this led to the idea, confirmed by experiment, that edrophonium would be a more effective antagonist of Org NC 45 than of most other neuromuscular blocking drugs. Edrophonium was about 12 times less potent than neostigmine in antagonizing Org NC 45. However, with equipotent antagonistic doses, edrophonium restored transmission to control (as measured by the train-of-four test) at least twice as rapidly as neostigmine and, more importantly, edrophonium had a much weaker effect than neostigmine on the cardiac vagus. The results obtained in cats with edrophonium were essentially confirmed in preliminary studies on nine anaesthesized patients. In these studies, a dose of edrophonium 0.5 mg kg-1 i.v. was found to produce adequate and rapid antagonism of Org NC 45, and because of the relatively weak side-effects of edrophonium, it was necessary, about 30 s before edrophonium, to administer only 0.6 mg of atropine (about 9 micrograms kg-1), which is half the dose commonly used when neostigmine is the reversal agent. These preliminary observations in man suggest that edrophonium may be the reversal agent of choice for Org NC 45.

Adult↗
PubMed1981

Pharmacokinetics of edrophonium and neostigmine when antagonizing d-tubocurarine neuromuscular blockade in man.

The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients anesthetized with halothane and nitrous oxide. After an intravenous (iv) injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to five per cent of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6), was then given iv in combination with atropine, 1.0 mg, as a 2-min controlled infusion. Train-of-four and single twitch tension were followed for 60 min in all patients. Twelve patients were monitored for 90 min, six patients for 120 min, four patients for 150 min, and two patients for 240 min. Blood was sampled intermittently for four hours and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium was found to promptly antagonize the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of less than 2 per cent of control per min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 +/- 0.21 (+/-SE) min as compared to 6.1 +/- 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was not significantly different. Except for a longer distribution half-life, the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination half-lives of edrophonium and neostigmine were 110 +/- 34 min (mean +/- SD) and 77 +/- 47 min, respectively. The authors therefore conclude that edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained, and effective antagonism of d-tubocurarine neuromuscular blockade.

Adult↗
PubMed1994

Edrophonium for the antagonism of neuromuscular blockade in dogs.

Neuromuscular, electrocardiographic and autonomic nervous changes were studied when edrophonium and four combinations of edrophonium and atropine were used to antagonise vecuronium-induced neuromuscular blockade in 87 dogs anaesthetised with halothane. Edrophonium (500 micrograms/kg body-weight) was given alone, or with atropine (40 micrograms/kg) or one minute after a dose of 600 micrograms of atropine, and a lower dose of edrophonium (250 micrograms/kg) was used with high (40 micrograms/kg) and low (20 micrograms/kg) doses of atropine. The neuromuscular blockade was antagonised when some recovery was present. The reversal was rapid and complete in 75 cases, but the remaining 12 dogs which received the low dose of edrophonium required a second injection. Trials with the high dose of edrophonium alone were discontinued because cardiac arrest occurred in one dog and bronchosecretion with profuse salivation in another. The heart rate increased with the low dose of edrophonium and the high dose of atropine, and increased and then decreased when edrophonium was followed by 600 micrograms of atropine. The heart rate was stable when the high and low doses of atropine and edrophonium were matched. All the treatments caused atrioventricular blockade. Non-cardiac autonomic changes (salivation and bronchosecretion) occurred in only two of the 87 dogs.

Anesthesia, Intravenous↗
PubMed1982

Edrophonium: duration of action and atropine requirement in humans during halothane anesthesia.

Edrophonium's onset and duration of antagonism (n = 26) and atropine requirement (n = 24) were determined under conditions of d-tubocurarine (dTc) neuromuscular blockade and halothane, nitrous oxide anesthesia. Results are compared with previous work in our laboratory on neostigmine and pyridostigmine under similar conditions. dTc was administered by continuous infusion to maintain a 90% depression of muscle twitch tension. Edrophonium (0.03-1.0 mg/kg) was injected as an iv bolus in combination with atropine (0.5 mg). dTc infusion was continued until a stable 90% depression of muscle twitch tension was reestablished. Time-to-peak effect (onset of action), duration, and magnitude of antagonism were recorded. The atropine requirement was determined during spontaneous recovery from dTc (0.3 mg/kg) and stable halothane, nitrous oxide anesthesia. Edrophonium (0.5 mg/kg) was mixed with 7, 15, or 30 micrograms/kg of atropine and compared to neostigmine (0.043 mg/kg) and atropine (15 micrograms/kg). Blood pressure, heart rate, and rhythm were recorded for 60 min following edrophonium administration. The time-to-peak antagonism for edrophonium (0.8-2.0 min) was far more rapid than neostigmine (7-11 min) or pyridostigmine (12-16 min). The ED50 for edrophonium was 0.125 mg/kg, however, the dose-response curve was not parallel to those for neostigmine or pyridostigmine. In equiantagonistic doses, the duration of antagonism by edrophonium (66 min) did not differ from neostigmine (76 min), but was shorter than pyridostigmine. Edrophonium required one-half the amount of atropine as did neostigmine to prevent bradycardia. The authors concluded that edrophonium has a more rapid onset than neostigmine and an equivalent duration of antagonism, and requires less atropine to prevent bradycardia.

Anesthesia, General↗
PubMed1996

Different properties of the bradycardia produced by neostigmine and edrophonium in the cat.

PURPOSE: The bradycardia produced by neostigmine and edrophonium was examined according to its relation to cholinesterase inhibition and to its sensitivity to block by muscarinic receptor antagonists. For comparison, the ability of muscarinic antagonists to block the bradycardia produced by electrical stimulation of the vagus nerve was determined. METHODS: Cats were anaesthetized, vagotomized and propranolol-treated. Heart rate was continuously recorded. Erythrocyte cholinesterase activity of arterial blood was measured using a radiometric technique. The right vagus nerve was isolated for electrical stimulation. The muscarinic antagonists used were atropine, glycopyrrolate, pancuronium, gallamine, and AFDX-116. RESULTS: Neostigmine produced a dose-dependent decrease in cholinesterase activity which reached a plateau at a cumulative dose of 0.16 mg.kg-1 (ED50 0.009 +/- 0.003 mg.kg-1). Neostigmine produced a dose-dependent decrease in heart rate with the dose-response relationship (ED50 0.1 +/- 0.01 mg.kg-1; P = 0.0006) shifted to the right of that for the inhibition of cholinesterase activity. In contrast to the anticholinesterase effect, the bradycardic effect did not reach a plateau and continued to increase even at doses at which the cholinesterase inhibition was maximal. The maximal decrease in heart rate when the heart was still in sinus rhythm was by 81 +/- 13 bpm (49 +/- 7% of baseline), which was produced by a dose of 0.32 mg.kg-1. Edrophonium produced dose-dependent decreases in cholinesterase activity and heart rate, which were highly correlated (correlation coefficient r = 0.99, P < 0.0001). The ED50 of the reduction in heart rate (0.9 +/- 0.18 mg.kg-1) and cholinesterase activity (0.89 +/- 0.12 mg.kg-1) produced by edrophonium were similar. Moreover, the reduction in heart rate and cholinesterase activity produced by edrophonium reached a plateau at the same dose (6.4 mg.kg-1). At this dose, heart rate decreased by 22 +/- 2 bpm (14.6 +/- 0.9% of baseline). Compared to the bradycardia produced by stimulation of the vagus nerve, that produced by neostigmine was blocked by muscarinic antagonists at significantly lower doses while that produced by edrophonium was blocked at similar doses. CONCLUSIONS: The neostigmine-induced bradycardia is poorly correlated with cholinesterase inhibition compared to that produced by edrophonium, and has a higher sensitivity to muscarinic receptor antagonists compared to that produced by edrophonium or vagus nerve stimulation. These results are consistent with the hypothesis that the neostigmine-induced bradycardia is, in part, the result of neostigmine directly activating cholinergic receptors within the cardiac parasympathetic pathway. The bradycardia produced by edrophonium may be accounted for solely by an anticholinesterase action.

Acetylcholine↗
PubMed1997

[Neostigmine and edrophonium. Antagonism of profound and shallow mivacurium blockade].

UNLABELLED: Mivacurium has a short duration of action because it is rapidly hydrolysed by plasma cholinesterase. There is ongoing controversy concerning the antagonism of mivacurium-induced neuromuscular block, firstly because of its short spontaneous recovery time, and secondly because the metabolism of mivacurium may be inhibited by anticholinesterases. We therefore compared neostigmine and edrophonium reversal of deep and moderate mivacurium-induced blocks. METHODS: After approval by the local ethics committee, 48 ASA class I and II adult patients were investigated during nitrous oxide-fentanyl-thiopental anaesthesia using train-of-four (TOF) stimulation and monitoring of the isometric force of adduction of a thumb. The patients received 0.2 mg/kg mivacurium i.v. Neuromuscular transmission was allowed to recover spontaneously in 10 patients (group SP). In 2 other groups the neuromuscular block was antagonised by administration of 0.04 mg/kg neostigmine (group N5; n = 9) or 1.0 mg/kg edrophonium (group E5; n = 10) when T1 had recovered spontaneously to 5% of control. In two other groups the neuromuscular block was antagonised with the same doses of neostigmine or edrophonium in 10 patients (group N25) and 9 patients (group E25), respectively, when T1 had recovered spontaneously to 25% of control. RESULTS: Neostigmine or edrophonium administered when T1 had recovered spontaneously to 25% of control shortened the recovery time (time from administration of ant-agonist to a T4/T1-ratio of 0.7) significantly from 10.7 +/- 2.2 min (mean +/- SD) in the SP group to 5.1 +/- 2.0 and 5.3 +/- 1.5 min in the N25 and E25 groups, respectively (P < 0.05). The corresponding recovery times in the SP, N5, and E5 groups were 15.9 +/- 2.9, 10.0 +/- 1.9, and 7.7 +/- 2.2 min, respectively. The difference between the SP and E5 groups was significant (P < 0.05). The recovery indices (time from 25% to 75% recovery of T1) of 3.0 +/- 1.3 and 1.7 +/- 0.9 min for the E5 and E25 groups, respectively, were shorter than those of the SP group at 6.1 +/- 2.0 min (P < 0.05). CONCLUSIONS: Two theoretical reasons, the very rapid onset time and the fact that it does not inhibit plasma cholinesterase, suggest edrophonium to be the preferred antagonist of a mivacurium-induced blockade. These two characteristics are reflected in our results: only edrophonium was able to shorten the recovery index significantly and, administered at a profound level of mivacurium-induced neuromuscular block, only edrophonium was successful in shortening recovery time significantly. Therefore, edrophonium should be the anticholinesterase of choice to antagonise a mivacurium-induced neuromuscular block.

Adolescent↗
PubMed1996

Quaternary nitrogen compounds affect carnitine distribution in rats. Particular emphasis on edrophonium.

Edrophonium (ethyl(m-hydroxyphenyl)dimethylamine) acutely modifies carnitine levels in different rat tissues, increasing hepatic and reducing blood and renal levels. After 2 h edrophonium treatment, the total serum carnitine levels were decreased by 16 (P < 0.001) and 33 (P < 0.001) percent in fed and fasted rats respectively compared to control, and in kidney the levels decreased by 11 (P < 0.05) and 34 (P < 0.001) percent whereas in liver the edrophonium treatment increased the levels by 43 (P < 0.001) and 59 (P < 0.001) percent. The edrophonium action does not depend on the route of administration or on the nutritional state of the animal. Its activity on carnitine levels is neither accompanied by significant variation of serum parameters of carbohydrate, fat and protein metabolism nor of insulin levels. The edrophonium activity is not related to cholinergic action, as physostigmine and ambenonium at concentrations known to increase cholinergic activity do not modify carnitine distribution in tissues. Trimethylphenylammonium (TPA) and trimethyl(p-aminophenyl)ammonium (TPA.NH2), compounds structurally similar to edrophonium, are on the contrary active on levels of carnitine and this effect is not related to their cholinergic potency. In 24 h fasted rats after the TPA and TPA. NH2 treatment, the total serum carnitine levels were decreased by 32 (P < 0.001) and 13 (n.s.) percent respectively compared to control, and in kidney the levels decreased by 15 (P < 0.02) and 5 (n.s.) percent, whereas in liver the treatment increased the levels by 72 (P < 0.001) and 45 (P < 0.01) percent. Moreover atropine, an acetylcholine antagonist, affects carnitine distribution in a way similar to edrophonium. Edrophonium activity on carnitine distribution, probably affects (inter)cellular carnitine transport by direct action on plasma membrane. Effect on capillary endothelium may be responsible for its observed action on muscle contraction force in imminent ischemia.

Ambenonium Chloride↗
PubMed1988

Edrophonium-induced inward membrane current in single neurons physically isolated from Aplysia californica.

The action of edrophonium on Aplysia neurons was studied using a concentration clamp technique which combines internal perfusion and a rapid drug application. Edrophonium elicited a dose-dependent inward current in the concentration range 10(-6) to 10(-4) M. At higher concentrations (10(-3) and 10(-2) M), the amplitude of the current often decreased and there was a rapid decay of the current. At these high concentrations, the current increased immediately after washing the neuron with normal solution. These results suggest that edrophonium blocks the ion channel which it opens. Removal of Na+ from the external solution greatly reduced the current amplitude by more than 90%. Removal of Ca2+ also reduced the amplitude of the response; however an increase of Ca2+ did not augment the response. These results suggest that Ca2+ does not carry the current, but is necessary for generation of an Na+-dependent inward current. Edrophonium, 10(-2) M, which completely blocked the current it induced within 20 s, did not significantly affect the voltage-dependent Na+ current. Tetrodotoxin, 1 x 10(-6) M, did not affect the edrophonium response. Hexamethonium, 1 x 10(-4) M, did not change the response elicited by edrophonium, while it significantly reduced the ACh response mediated by Na+. In some neurons edrophonium elicited an inward current, but ACh induced an outward current. Therefore the Na+ channels opened by edrophonium appear to be distinct from both the voltage-gated and ACh receptor-operated Na+ channels.

Acetylcholine↗