SEARCH · PubMed Health

Results for “Decamethonium Compounds”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources

PubMed1985

Partial neuromuscular blockade and cardiovascular responses to static exercise in man.

In human subjects sustained static contractions of the quadriceps femoris in one leg were performed with the same absolute and the same relative intensity before and after partial neuromuscular blockade with either decamethonium or tubocurarine which reduced strength to about 50% of the control value. During the contractions performed with the same absolute force, the magnitude of the cardiovascular responses (heart rate and blood pressure) was greater during neuromuscular blockade than during control contractions. During the contractions involving the same relative force the magnitude of the cardiovascular responses was almost the same with and without neuromuscular blockade. These findings were independent of the drug used. The metabolic part of the exercise pressor reflex was assessed by the application of an arterial cuff 1/2 min before cessation of exercise and for the following 3 min of rest. Although heart rate and blood pressure decreased after cessation of exercise, application of the tourniquet resulted in higher post-exercise values and this effect was seen both with and without neuromuscular blockade. Muscle biopsies from the subjects' m. vastus lateralis were analysed for fast- and slow-twitch fibre composition showing 27-66% slow-twitch fibres. No correlation was found between cardiovascular responses to static exercise, with or without neuromuscular blockade, and fibre type predominance. The results suggest that the involvement of fast- or slow-twitch muscle fibres does not play a dominant role in the cardiovascular responses to static exercise in man. Both central command and reflex neural mechanisms are of importance, and it appears that these two control mechanisms are redundant and that neural occlusion may be operative. However, when partial neuromuscular blockade induces a disproportion between an increase in central command and a constant or decreasing muscle tension and metabolism, the larger signal arising from central command determines the magnitude of the cardiovascular responses.

Adult↗

PubMed1985

Heart rate at the onset of static exercise in man with partial neuromuscular blockade.

In human subjects the length of the first complete cardiac cycle after the onset of static finger or hand muscle contractions was recorded. Graded contractions as well as maximal contractions in which muscle fatigue was provoked by ischaemia were studied. Maximal finger muscle contractions were also weakened by partial neuromuscular blockade with either decamethonium or tubocurarine. The change in R-R interval at the onset of exercise was variable and in part dependent on the length of the last R-R interval before the onset of exercise. The largest decreases were seen when the preceding R-R interval was long. During graded submaximal and maximal contractions a correlation was demonstrated between the change of the R-R interval at the onset of exercise and the contraction intensity. At the onset of the weakest contractions a 3% prolongation of the R-R interval was seen while the strongest contractions were associated with a shortening of 8%. At the onset of all maximal contractions, whether fatigued due to ischaemia or weakened by decamethonium or tubocurarine, a decrease in R-R interval was seen independent of the force developed. When compared at the same resting R-R interval, contractions performed with hand muscles elicited a greater shortening of R-R interval than contractions with finger muscles. The results suggest that the initial change in heart rate at the onset of static muscle contractions is related to the voluntary effort rather than to the force developed, the state of the working muscles or to the type of muscle fibres involved. It may thus be elicited by 'cortical irradiation' rather than by a 'muscle-heart reflex'. Its size depends on the length of the preceding R-R interval, the intended contraction intensity and the muscle mass involved.

Adult↗

PubMed1987

Effect of channel blockers on potassium efflux from metabolically exhausted frog skeletal muscle.

1. 86Rb and 42K have been used to assess potassium exchange in frog skeletal muscle which had been metabolically exhausted by electrical stimulation (1 Hz) after treatment with 2 mM-cyanide and 1 mM-iodoacetate. These conditions led to the development of rigor. 2. Poisoning by itself induced a small but variable increase in tracer efflux. Complete mechanical exhaustion subsequent to electrical stimulation was, however, accompanied by a 5-6 fold increase in the rate coefficient for both 86Rb and 42K efflux. In the case of rubidium this was maintained for at least 20 min and often for up to 1 h. 3. The increase in tracer efflux induced by metabolic exhaustion was inhibited by barium (0.03-5 mM) in a reversible and concentration-dependent manner. Inhibition was also observed with glibenclamide (3-100 microM), tolbutamide (0.3-2 mM), TEA (5-100 mM) and the local anaesthetics lignocaine (1-3 mM) and tetracaine (1 mM). Quinine produced a dual response consisting of an inhibitory component which was most clearly seen at low concentrations (0.3 mM) and an enhancement of tracer efflux that became increasingly dominant at higher concentrations (1-10 mM). 4. Both apamin (30 and 100 nM) and Israeli scorpion (Leiurus quinquestriatus) venom (16 micrograms ml-1) produced little or no block of the tracer efflux activated by metabolic exhaustion. Similarly 4-aminopyridine (3 mM) and decamethonium (0.3 mM) were without obvious effect. 5. It is concluded that metabolic exhaustion of frog skeletal muscle leads to an increased permeability to both 42K and 86Rb. Our results with channel blockers suggest that this K+ permeability can be attributed neither to the delayed rectifier nor to an apamin- or charybdotoxin-sensitive calcium-activated K+ permeability (PK(Ca) but may be predominantly due to activation of ATP-sensitive channels similar to those found in the beta-cells of pancreatic islets.

4-Aminopyridine↗

PubMed1987

The role of the sodium pump during prolonged end-plate currents in guinea-pig diaphragm.

1. Depolarization caused by carbachol or decamethonium is followed by spontaneous recovery of membrane potential in the presence of the drug. The involvement of the Na pump in this recovery has been investigated in guinea-pig diaphragm at 37 degrees C. 2. Restoration of potassium ions (K+) to the bathing solution gives a rapid recovery of membrane potential which is compatible with a component of recovery of potential being attributable to an electrogenic ion pump and from which a Na pump current of over 60 nA has been estimated. 3. The maintenance of membrane potential in the presence of depolarizing drugs is interpreted in terms of a residual rate of channel opening at a time when the membrane potential is restored, balanced by Na pump action producing tubular depletion of K+. To account for these results a Na pump conductance has been added to a model circuit of drug action. 4. The peak end-plate current produced by carbachol (80 microM) is 100 nA (n = 11) as recorded by the voltage clamp technique; similar estimates may be obtained from measurements of input resistance which falls to 31% of the initial value (n = 5). In muscles desensitized by carbachol for 30 min the end-plate current is 11 nA. 5. In normal muscle removal of K+ from the bathing solution produces a reversible hyperpolarization. In muscles where the membrane potential has recovered in the continued presence of the drug, a hyperpolarization is also found on removal of K+. Withdrawal of K+ during the early stage of spontaneous recovery of potential produces a depolarization or an arrest of the spontaneous repolarization. These results are interpreted in terms of the Na pump producing different effects during the course of spontaneous repolarization. 6. Indirect evidence for K+ depletion in the transverse tubules by the Na pump is provided by an increased resistance to inward current following brief exposure to carbachol or decamethonium. A similar mechanism is used to interpret both the observed change in end-plate revérsal potential to a more negative value and the marked diminution in the amplitude of the action potential at the end-plate during drug action.

Action Potentials↗

PubMed1991

Activation of ion channels in the frog endplate by several analogues of acetylcholine.

1. Single-ion-channel recording has been used to estimate the equilibrium concentration-response relationship for several acetylcholine analogues. The response, corrected for desensitization, was taken as the probability of a channel being open during clusters of openings that were separated by desensitized periods. 2. All agonists were able to block the channels which they themselves opened. Carbachol, suberyldicholine and the sulphonium analogue of acetylcholine were all found to be efficacious agonists in the sense that the results indicate that all of them, in sufficiently high concentration, would be able to open 90% or more of channels if it were not for channel block. 3. In the case of suberyldicholine the results are much as predicted by the interpretation of the fine structure of channel openings at low agonist concentrations. 4. The maximum probability of opening that could be obtained with decamethonium and with phenyltrimethylammonium was low (below 4%), and it was not possible to distinguish whether this was wholly a result of the powerful (relative to activation potency) channel-blocking action of these agonists, or whether it was to some extent attributable to their being genuine partial agonists. 5. The results suggest that, for a range of agonists, differences in equilibrium potency are usually more strongly influenced by affinity for binding to the resting state of the receptor than by ability to activate the receptor once bound, though in the case of suxamethonium (relative to acetylcholine) the contributions of each factor are similar.

Acetylcholine↗

PubMed1993

Activation of nicotinic acetylcholine receptors on cultured Drosophila and other insect neurones.

1. Using whole-cell and single channel recordings, we have examined the properties of acetylcholine (ACh)-activated currents in neurones from larval and pupal Drosophila melanogaster (fruit fly), larval and embryonic Musca domestica (house fly), and nymphal Schistocerca gregaria (locust). 2. In all preparations, single channel recordings revealed two major classes of ACh-activated channels, with average conductances of approximately 32 and 59 pS. 3. At ACh concentrations from 1 to 10 microM, channel activity in Drosophila larval neurones occurs in bursts with an average of 1-2 openings. Open times and burst durations are described by one or two exponentials. Burst durations for the 32 pS channel (approximately 3 ms, slow component) were longer than those for the 59 pS channel (approximately 1.0 ms). The mean open interval duration for the 32 pS channel (slow component) was also longer than that of the 59 pS channel. 4. At high ACh (20-200 microM) concentrations, bursts of the smaller conductance channel occur in clusters separated by long-lived periods without channel activity. Considerable kinetic heterogeneity was observed among clusters. 5. The whole-cell dose-response curve suggests that activation of current by ACh increases up to at least 100 microM and that multiple ligand binding steps are involved. 6. Drosophila and Musca larval neuronal ACh-activated channels show some unique features in their cholinergic pharmacological properties: (a) they are only weakly activated by the potent neuromuscular nicotinic agonist suberyldicholine, (b) hexamethonium and decamethonium are weak, but approximately equi-effective blockers, and (c) alpha- and kappa-bungarotoxin (BTX) both blocked reversibly, though alpha-BTX appears to be the more potent inhibitor.

Acetylcholine↗

PubMed1998

Acceleration of oxime-induced reactivation of organophosphate-inhibited fetal bovine serum acetylcholinesterase by monoquaternary and bisquaternary ligands.

Reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by oximes is the primary reason for their effectiveness in the treatment of OP poisoning. Reactivation is reported to accelerate by quaternary ligands such as decamethonium, which is devoid of nucleophilicity. The mechanism of this enhancement is not known. To better understand the acceleration phenomenon, we examined ligand modulations of oxime-induced reactivation of methylphosphonylated AChE using 7-(methylethoxyphosphinyloxy)-1-methylquinolinium iodide and fetal bovine serum AChE. Edrophonium, decamethonium, and propidium, three quaternary AChE ligands of different types, were tested as potential accelerators. Experiments were carried out with both soluble enzyme preparation and AChE conjugated to polyurethane. Kinetic measurements with oximes 2-[hydroxyiminomethyl]-1-methylpyridinium chloride, 1,1'-trimethylene bis-(4-hydroxyimino methyl)-pyridinium dibromide, and 1, 1'-[oxybis-methylene)bis[4-(hydroxyimino)methyl]pyridiniu um dichloride showed that in the presence of 50 microM edrophonium, the reactivation rate constants increased 3.3-12.0-fold; 200 microM decamethonium produced a 1.6-3.0-fold enhancement of reactivation rate constants by the same oximes. Reactivation of the inhibited enzyme by 1-(2-hydroxyiminomethyl-1-pyridinium)-1-(4-carboxy-aminopyridinium )-d imethyl ether hydrochloride, 1-(2-hydroxyiminomethyl-1-pyridinium)-1-(3-carboxy-aminopyridinium )-d imethyl ether hydrochloride, and 1-[[[4-(aminocarbonyl)pyridino]methoxy]methyl]-2, 4, -bis(hydroxyimino)methyl pyridinium dichloride was not affected by either ligand. Propidium slowed the reactivation of 7-(methylethoxyphosphinyloxy)-1- methylquinolinium iodide-inhibited AChE by all oximes. Results suggest that the accelerator site may reside inside the catalytic gorge rather than at its entrance and acceleration may be due to the prevention of reinhibition of the regenerated enzyme by the putative product, the phosphonylated oxime. In addition to the nucleophilic property of the oximate anion, some of the reactivators may carry an accelerating determinant, as characterized with respect to edrophonium and decamethonium. Results offer possible explanations for the superiority of 1-(2-hydroxyiminomethyl-1-pyridinium)-1-(4-carboxy-aminopyridinium )-d imethyl ether hydrochloride over other oximes in the reactivation of specific AChE-OP conjugates.

Acetylcholinesterase↗

PubMed1967

Electrical phenomena associated with the activity of the membrane-bound acetylcholinesterase.

Treatment of isolated electroplax with physiological solutions supplemented with either 1 molar sodium chloride, 2 molar urea, or 2 molar sucrose renders the cell insensitive to carbamylcholine, phenyltrimethylammonium, or decamethonium even at high concentrations. The treated cells have a residual resting potential of -20 +/- 10 millivolts (negative inside) and are depolarized by acetylcholine at concentrations larger than 10(-3) mole per liter. This response is not affected by d-tubocurarine but is blocked by physostigmine, diisopropylphosphorofluoridate, or strong buffers and thus depends on the catalytic activity of the membrane-bound acetylcholinesterase.

Acetylcholinesterase↗

PubMed1971

Acetylcholine binding to Torpedo electroplax: relationship to acetylcholine receptors.

Binding of [(3)H]acetylcholine to a particulate fraction of Torpedo electroplax was measured by equilibrium dialysis. Two high-affinity sites present on phospholipoproteins bound acetylcholine reversibly, and binding was blocked by nicotinic drugs. Characteristics of this binding suggest that these phospholipoproteins may be acetylcholine receptors.

Acetylcholine↗

PubMed1952