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

Backman, Steven B.; Stein, Reuben D.; Blank, David; Collier, B.; Polosa, Canio

doi:10.1007/bf03017959

Cited by 19 publications

(21 citation statements)

References 32 publications

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“…In fact, we have demonstrated, in the cat, that the range of dose ofedrophonium which blocks the bradycardia produced by electrical stimulation of the vagus nerve 4 overlaps that which blocks cholinesterase activity. 13 In a previous study in bilaterally vagotomized, propranolol-treated cats, we reported that edrophonium at a dose < 1.5 mg.kg -1 augmented the bradycardia evoked by electrical stimulation of the distal sectioned portion of the vagus nerve, presumably secondary to the facilitation of transmission in the cardiac parasympathetic pathway due to the anticholinesterase action of edrophonium. 4,1s However, at doses > 1.5 mg.kg -1, edrophonium blocked the bradycardia evoked by stimulation of the vagus nerve.…”

Section: Discussionmentioning

confidence: 81%

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission

Stein¹,

Backman

Collier³

et al. 1998

Can J Anaesth

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Laboratory Reports Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmissionPurpose: 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 pM), neostigmine (0. I -I 0/~M), and muscarinic M and M 2 antagonists pirenzepine and AFDX-I 16 (200 nM-I 0 pM), respectively. To eva uate a presynapt c act on, the effect of edrophonium on basal and high-K + (35 mM) evoked re ease 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 pg) into the superior cervical ganglion was determined in vivo.

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Section: Discussionmentioning

confidence: 81%

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission

Stein¹,

Backman

Collier³

et al. 1998

Can J Anaesth

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“…In addition, this possibility seems unlikely because of the finding in a previous study that with edrophonium, there is a close correlation between the magnitude of the inhibition of erythrocyte cholinesterase activi~ and bradycardia suggesting that cholinesterase activity in the heart is inhibited by doses of anticholinesterase which are similar to those required to inhibit red cell cholinesterase. 4 The similarity between the properties of the bradycardia produced by pyridostigmine and physostigmine and those of the bradycardia evoked by neostigmin e suggest that the bradycardia produced by anticholinesterases containing a carbamyl group is mediated by similar mechanisms. Previously, we have hypothesised that the bradycardia produced by neostigmine is caused by direct activation of cholinergic receptors in the peripheral cardiac parasympathetic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…These observations are reminiscent both qualitatively and quantitatively of the findings observed with neostigmine, s,4 The bradycardia produced by edrophonium, in contrast, demonstrates similar sensi-tivity to block by muscarinic M 2 antagonists compared to that produced by vagus nerve stimulation and is insensitive to block by nicotinic receptor antagonists. 3,4 Because the anticholinesterases were administered as bolus doses, rather than by continuous infusion, steadystate drug levels were not achieved. Nevertheless, since the objective was to correlate two biological end-points, namely the reduction in heart rate and inhibition of cholinesterase activity, the actual drug levels were irrelevant.…”

Section: Discussionmentioning

confidence: 99%

“…4 Cholinesterase activity was determined on arterial blood samples prior to (control) and following injection of increasing doses of pyridostigmine (n = 4) or physostigmine (n = 4) when heart rate had reached a steady-state at each dose. Aliquots, 100 pl, of freshly collected heparinised blood were pre-incubated with the butylcholinesterase inhibitor IS0-OMPA (10 }aM, 22~…”

Section: Methodsmentioning

confidence: 99%

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Bradycardia produced by pyridostigmine and physostigmine

et al. 1997

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The bradycardia produced by pyridost]gmine and physos"dgrnine in an animal model of acute cardiac denervation was examined according to its relation to cholinesterase inhibition and sens~ to block by d~inergic receptor antagonists.Methods: Cats were anaesthetised, vagotomisecl and propranolo~tmated. Heart rate was continuously recorded. Erythrocyte cholines~rase activity of arterial blood was measured using a radiometric technique. Nicotinic and muscarinic M~ receptors were blocked with hexamethonium and pirenzepine, respeclm~ly. M 2 receptors were blocked with gallarnine, pancuronium and AFDX-116. Results: W~ pyridostigrnine and physostigmine, the close-response relationship for the decrease in heart rate (EDs0 1,05 -0.25 and 0.198 ---0.03 mg.kg -j, respectively)was shiff~ to the right of that for the inhibition of cholinesterase activity (ED m 0,094 + 0.03 and 0.032 -0.01 mg'kg -j, respectively). The decrease in cholinesterase activity reached a plateau at a cumulative dose of 0.56 ---0.08 and 0.32 --+ 0.08 rng.kg -~, respectively. In contrast, there did not appear to be a plateau in the bradycardic effect. The bradycardia produced by pyridostigrnine and physoslJgmine was blocked by hemmethonium (F..Ds010 _ 1.3 and 15.3 +-2.4 mg-kg -I, respectively), pirenzepine (EDs068 __. 16 and 138 +_ 32/ug.kg -t, respectively), gallamine (56 -+ II and 67 -+ 17 pg.kg -I , respectively ), pancuronium 02 -+ 10 and 30 -+ 4 pg'kg -t, respectively), and AFDX-I 16 (31 + 4 and 28 +-4/~g'kg -~, respectively). Condmiom The bradycardia produced by reversible anticholinesterase drugs containing a carbamyl group is not dearly related to the degree of cholinesterase activity, and has a low sensitivity to nicotinic and muscarinic M, and a high sem~ to muscarinic M 2 re~ptor antagonists.Objeetif : Examiner si la bradycardie provoquEe par la physo~grnine et la pyridostigrnine sur un mod61e de d~-nervation cardiaque animal est en rapport avec I'inhibition de la cholinest&ase et la sensibilitE au bloc du r~cepteur cholinergique par ses antagonistes. M~hod~ : Des chats ont Et6 anesthEsiC~s, vagotomisEs et trait& au propanolol. Leur frEquence cardiaclue a 6t6 enregistr~ continuellement. Une technique radion'Wuique a permis de mesurer dans le sang art~riel I'actMt' E de la cholinest~rase &ythrocytaire. On a bloquE les rvacepteurs nicotiniques avec de I'hexamC~onium et les rEcepteurs muscariniques M. avec de la pirenz6pine. Les r&:epteurs M z &alent bloclu~s avec de la gallamine, du pancuronium et de I'AFDX-I I g.

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“…However, recent studies suggest that anticholinesterases may have additional effects at cholinergic synapses within the autonomic peripheral pathway. For example, in vivo and in vitro animal studies suggest that neostigmine and edrophonium directly activate (Backman et al, 1993a(Backman et al, , 1996a and inhibit (Backman et al, 1997;Stein et al, 1998), respectively, these cholinergic receptors. Thus, the parasympathomimetic action of the anticholinesterases must be understood within the context of their anticholinesterase activity on the one hand, and their direct interaction with cholinergic receptors on the other.…”

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confidence: 99%

Effects of the Anticholinesterase Edrophonium on Spectral Analysis of Heart Rate and Blood Pressure Variability in Humans

Deschamps

Backman²,

Novak³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Edrophonium, an anticholinesterase, exerts a biphasic effect on cardiovascular autonomic drive in humans (lower doses enhance; higher doses reduce). Twenty-five anesthetized, mechanically respired (10 breaths ⅐ min Ϫ1 , constant tidal volume) patients were given either saline (n ϭ 10) or edrophonium (0.01-1.0 mg ⅐ kg Ϫ1 , n ϭ 15) following surgery. ECG, radial arterial pressure, and respiratory rate were sampled at 250 Hz to obtain time series for consecutive R-R intervals (RRIs), and systolic (SBP) and diastolic blood pressure (DBP). A Wigner distribution was used for time frequency mapping of spectral powers at high (HFP, 0.15-0.5 Hz) and low (LFP, 0.0 -0.05 Hz) frequency. Edrophonium produced a dose-dependent decrease in heart rate [baseline 66.8 Ϯ 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 Ϯ 1.4 beats per minute with 1.0 mg ⅐ kg Ϫ1 , P Ͻ 0.01]. HFP of the RRI increased at low doses (0.2-0.4 mg ⅐ kg Ϫ1 ; maximum increase to 111.0 Ϯ 58.2% baseline; P Ͻ 0.01) but decreased (Ϫ49.5 Ϯ 35.5% baseline; P Ͻ 0.01) at higher (1.0 mg ⅐ kg Ϫ1 ) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to Ϫ26.2 Ϯ 7.5% baseline, P Ͻ 0.01, 1.0 mg ⅐ kg Ϫ1 ). LFP of SBP was also decreased (Ϫ46.3 Ϯ 10.9% baseline, P Ͻ 0.01, 1.0 mg ⅐ kg Ϫ1 ). Edrophonium may enhance (lower dose) or reduce (higher dose) cardiovascular autonomic drive in humans, as evidenced by the significant changes it evokes in HFP of the RRI (parasympathetic drive), and in the HFP and LFP of SBP (sympathetic drive). These observations may account for the modest autonomic side effects of edrophonium when this drug is used clinically.

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

Cited by 19 publications

References 32 publications

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission

Synaptic inhibitory effects of edrophonium on sympathetic ganglionic transmission

Bradycardia produced by pyridostigmine and physostigmine

Effects of the Anticholinesterase Edrophonium on Spectral Analysis of Heart Rate and Blood Pressure Variability in Humans

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