PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Neostigmine”

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 19 recordsLinked to original sources
PubMed1977

Glycopyrrolate-neostigmine mixture for antagonism of neuromuscular block: comparison with atropine-neostigmine mixture.

Glycopyrrolate, a new anticholinergic agent, was evaluated and compared with atropine. Glycopyrrolate 0.2 mg to neostigmine 1.0 mg was found to be safe and effective. The heart rates remained more stable with glycopyrrolate, and the frequency of arrhythmia, which was both transient and of no consequence, was similar in the two groups. The antisialogogue action of glycopyrrolate was superior to that of atropine.

Anesthesia, General↗
PubMed1979

4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.

Adult↗
PubMedDate not supplied

Antagonism of pancuronium and its metabolites by neostigmine in cats.

Antagonism by neostigmine of neuromuscular blockade produced by pancuronium or its metabolites was studied in the cat anterior or tibialis muscle-peroneal nerve preparation using constant infusions of muscle relaxants. The ED50 of neostigmine (dose which caused a 50% antagonism) was 16, 11, 29, and 26 micrograms/kg for pancuronium, 3-hydroxypancuronium, 17-hydroxypancuronium, and 3, 17-hydroxypancuronium, respectively. Times of onset of neostigmine action were shorter when antagonizing 17-hydroxypancuronium neuromuscular blockade. Duration of neostigmine action when antagonizing 17- or 3, 17-hydroxypancuronium blockade was shorter than with pancuronium or 3-hydroxypancuronium. We conclude that more neostigmine is required to antagonize 17- or 3,17-hydroxypancuronium neuromuscular blockade than is required to antagonize pancuronium. Conversely, less neostigmine was required to antagonize 3-hydroxypancuronium blockade.

Animals↗
PubMed1978

Neostigmine-induced alterations at the mammalian neuromuscular junction. II. Ultrastructure.

Brief and chronic exposure of rats to neostigmine methylsulfate produced marked morphological alterations of the fine structure at the end-plate region of the extensor digitorum longus muscles. These changes were dose and time dependent and were restricted primarily to the subjunctional myofibrillar apparatus and membrane-bound organelles. In addition, significant presynaptic alterations were observed including synaptic vesicle depletion and the appearance of numerous coated vesicles and membrane cisternae, which indicated continuing nerve terminal hyperactivity. With chronic treatment, degeneration and partial recovery of the nerve axon also were observed. The morphological changes of the end-plate region induced by neostigmine did not occur in most fibers after brief denervation and were eliminated entirely by chronic nerve section. Thus, the postsynaptic degenerative changes caused by neostigmine treatment observed in nondenervated animals appear to result primarily from greatly increased synaptic activity and not primarily from a direct neostigmine reaction with the pre- or postsynaptic membranes. Since the myopathic changes observed in this study were produced by neostigmine, a drug which is commonly employed in the routine treatment of human patients with myasthenia gravis, continued use of neostigmine for long-term therapy in noncrisis situations may not be accepted as being free from risk.

Animals↗
PubMed1975

Neostigmine methylsulfate. Does it have a chronic effect as well as a transient one?

Three groups of 200-gm rats were injected subcutaneously with neostigmine methylsulfate (1 mg/kg/day) for 7, 30, and 100 days. Electrophysiological changes were assessed in vitro, using microelectrode techniques to examine diaphragm muscles of treated and untreated animals. Miniature end-plate potential (MEPP) amplitude decreased in neostigmine-treated preparations. Guanidine hydrochloride enhances transmitter release and increases MEPP frequency in control preparations. Neostigmine-treated animals examined between 6 to 72 hours after discontinuation of neostigmine therapy showed impaired response to the facilitating influence of guanidine. Recovery of response to guanidine was inversely related to length of treatment with neostigmine. Results of electron-microscopic examination of motor end-plates in treated animals revealed ultrastructural changes, including simplified end-plates, and, occasionally, multiple, separate, junctional regions. Therefore, the chronic administration of cholinesterase inhibitors in man may have a deleterious effect, as well as a transient beneficial one.

Animals↗
PubMed1975

The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade.

d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.

Acid-Base Equilibrium↗
PubMed1979

Pharmacokinetics and pharmacological effects of neostigmine in man.

1 The pharmacokinetics of neostigmine was studied in six patients during the reversal of neuromuscular block induced by tubocurarine chloride. The effect of the drug on neuromuscular function was simultaneously assessed by electromyography. 2 Neostigmine was rapidly eliminated from plasma after intravenous administration. The decline in the plasma concentration of the drug was invariably resolved into two exponential components. The fast disposition (distribution) half-life of the drug was invariably less than 1 min; the slow disposition (elimination) half-life ranged from 15.4--31.7 min. 3 Neostigmine usually increased the amplitude of the compound muscle action potential and diminished electromyographic decrement within 2 min of intravenous injection. The pharmacological effect of neostigmine was usually maximal between 7 and 15 min. There was an inverse relationship between the plasma concentration of the drug and the facilitation of neuromuscular transmission. 4 Red cell acetylcholinesterase activity was almost completely inhibited within 2--3 min of intravenous injection of neostigmine. Enzyme activity recovered to approximately 28% of control values by 30 min and to 55% by 60 min.

Acetylcholinesterase↗
PubMed1978

Plasma clearance of neostigmine and pyridostigmine in the dog.

1 The pharmacokinetics of neostigmine and pyridostigmine was studied in conscious dogs by the use of a cross-over design. 2 Both neostigmine and pyridostigmine were cleared from plasma in a biexponential manner. 3 The apparent volume of distribution of pyridostigmine was invariably greater than that of neostigmine, and its fast disposition half-life was approximately three times longer. 4 The whole body clearance and the urinary elimination of pyridostigmine was approximately twice that of neostigmine. 5 The slow disposition half-life of pyridostigmine was approximately three times longer than that of neostigmine, suggesting that the longer duration of action of pyridostigmine is related to the differential clearance of the two quarternary amines from plasma.

Animals↗
PubMedDate not supplied

The interaction between d-tubocurarine, pancuronium, polymyxin B, and neostigmine on neuromuscular function.

The interaction between pancuronium, d-tubocurarine, polymyxin B, and neostigmine was studied in the rat diaphragm-phrenic nerve preparation. Polymyxin B (5 mug/ml) did not affect twitch tension alone but decreased the pancuronium ED50 from 0.8 mug/ml to 0.32 mug/ml and the d-tubocurarine ED50 from 0.25 mug/ml to 0.15 mug/ml. Neostigmine (0.2 to 10 mug/ml) antagonized pancuronium or d-tubocurarine-induced depression of twitch tension. In contrast, neostigmine (0.001 to 0.2 mug/ml) augmented polymyxin B depression. Similarly, neostigmine (0.1 mug/ml) augmented combined polymyxin B-pancuronium or polymyxin B-d-tubocurarine depression of twitch tension. The authors conclude that polymyxin B potentiates the neuromuscular blockade from pancuronium or d-tubocurarine and that neostigmine further augments this block.

Animals↗
PubMedDate not supplied

[Effect of x-irradiation, nicotinic acid and neostigmine methylsulfate on the interrelation between methylation and biosynthesis of tRNA].

Experiments on rats established that tRNA of the liver under the effect of total X-irradiation (800 R), nicotinic acid and neostigmine methylsulphate proves to be hypermethylated. In this case tRNA molecules undergo conformation changes. Nicotinic acid and neostigmine methylsulphate administered to the animals under experiment an hour before irradiation favour the normalization of these indexes. As a rule, a correlation is observed between changes in methylation of tRNA and activity of their methylases. Irradiation inhibits the processes of tRNA synthesis which are normalized under the effect of nicotinic acid administered before the irradiation. Nicotinic acid and neostigmine methylsulphate produce no effect on synthesis of tRNA in the liver of normal animals. The activity of acid tRNase under the effect of nicotinic acid is not changed, under other conditions of the experiment it decreases. Irradiation against a background of nicotinic acid and neostigmine methylsulphate administered to animals and neostigmine methylsulphate administration to the intact animals inhibit the activity of alkaline tRNase.

Animals↗
PubMed1978

Acid-base balance and neostigmine antagonism of pancuronium neuromuscular blockade.

In 40 cases anesthetized with chloralose and urethane, pancuronium was infused i.v. at a constant rate to produce and maintain 90% depression twitch tension of the anterior tibialis muscle following supramaximal stimulation of the peroneal nerve. Neither respiratory alkalosis nor metabolic acidosis influenced the infusion rate required to produce 90% depression of twitch tension or antagonism of this depression yb neotigmine. Respiratory acidosis (pH 7.15; PaCO2 10 kPa) did not alter the required infusion rate but did prevent complete antagonism by neostigmine. Metabolic alkalosis (pH 7.65; PaCO2 4.8 kPa) reduced both the required infusion rate and prevented complete restoration of twitch tension by neostigmine. The duration of neostigmine antagonism was shortened by metabolic alkalosis. We conclude that respiratory acidosis and metabolic alkalosis prevent antagonism of pancuronium by neostigmine.

Acid-Base Equilibrium↗
PubMed1977

Pancuronium-induced neuromuscular blockade, and its antagonism by neostigmine, at 29, 37, and 41 c.

To determine the effects of variations in temperature on the neuromuscular blockade produced by pancuronium, the drug was infused intravenously into 18 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch tension of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean (+/-SE) infusion rates of pancuronium needed were 0.44 +/- 0.05, 0.99 +/- 0.11, and 1.05 +/- 0.09 microng/kg/min (r = 0.73) at 29, 37, and 41 C, respectively. In contrast, the doses of neostigmine necessary for 50 per cent antagonism of the pancuronium-induced depression of twitch tension were not significantly different at the three temperatures. The time required to achieve peak neostigmine effect was longer at the lowest temperature. The durations of neostigmine action were longer at 29 and 37 than at 41 C. It is concluded that hypothermia augments neuromuscular blockade produced by pancuronium and prolongs the time to peak effect, and possibly the duration of action, but not the dose of neostigmine needed to antagonize the blockade.

Anesthesia, Intravenous↗
PubMed1978

Effects on muscarinic receptors of various agents in reversal of neuro-muscular blockade: a study evaluating atropine, glycopyrron, neostigmine and pyridostigmine.

The effects were studied of various drug combinations, recommended for use in reversal of neuromuscular blockade, on heart rate and salivary secretions in 80 healthy patients anaesthetized with nitrous oxide-oxygen-halothane and relaxed with d-tubocurarine. The drug combinations were mixtures of atropine 1 mg--neostigmine 2.5 mg, atropine 1 mg--pyridostigmine 15 mg, glycopyrron 0.5 mg--neostigmine 2.5 mg, and glycopyrron 0.5 mg--pyridostigmine 15 mg, respectively. It was found that administration of the atropine-containing mixtures induced more pronounced initial increases and delayed decreases in heart rate than the mixtures containing glycopyrron. Pyridostigmine-containing mixtures elicited a somewhat more pronounced initial increase in heart rate than neostigmine-containing mixtures, but a less pronounced and delayed decrease in heart rate. Supraventricular arrhythmias occurred less frequently in the pyridostigmine groups than in the neostigmine groups. No such difference was found between the atropine and glycopyrron groups. Glycopyrron caused a more intense dryness of the mouth than atropine. A differential attitude towards the use of drugs for reversal of neuromuscular blockade, based on the cardiovascular state of the particular patient, might be recommendable.

Adolescent↗
PubMed1978

Potentiation of neostigmine and pyridostigmine by 4-aminopyridine in the rat.

The interaction between 4-aminopyridine and neostigmine or pyridostigmine was studied in vivo in the rat sciatic nerve-anterior tibialis preparation using the constant infusion of pancuronium technique. The ED50 (dose of drug which produced a 50% antagonism) of neostigmine, pyridostigmine and 4-aminopyridine were 18, 49 and 440 microgram kg(-1) respectively. The addition of 100 microgram kg(-1) of 4-aminopyridine, which produced no antagonism by itself, decreased the neostigmine ED50 to 7.4 microgram kg(-1). The addition of 200 microgram kg(-1) of 4-aminopyridine, which produced a 30% antagonism by itself, decreased the ED50 of pyridostigmine to 11 microgram kg(-1). We conclude that both neostigmine and pyridostigmine interact with 4-aminopyrine synergistically.

Aminopyridines↗
PubMedDate not supplied

Neostigmine and 4-aminopyridine antagonism of lincomycin-pancuronium neuromuscular blockade in man.

Seven anesthetized patients were studied to determine the interaction between pancuronium and lincomycin and the ability of neostigmine and 4-aminopyridine to antagonize the block. Lincomycin 600 mg given IV alone did not decrease twitch tension. An 8 to 10% decrease in twitch tension occurred when lincomycin was given after neostigmine antagonism of pancuronium. Lincomycin augmented a partial pancuronium neuromuscular blockade. The combined lincomycin-pancuronium neuromuscular blockade was effectively antagonized by both neostigmine and 4-aminopyridine although the latter produced a slower rate of antagonism. The authros conclude that lincomycin, 600 mg IV, augments a pancuronium neurovascular blockade. 4-Aminopyridine offers no advantage over neostigmine and, in fact, may offer a disadvantage because of a slower rate of antagonism.

Adolescent↗
PubMed1978

Neostigmine-induced alterations at the mammalian neuromuscular junction. I. Muscle contraction and electrophysiology.

The effects of single and repetitive injections of neostigmine on neuromuscular physiology were examined in rat extensor digitorum longus muscles. The characteristic facilitation of neuromuscular transmission associated with acute anticholinesterase treatment was accompanied by significant pre- and postsynaptic alterations in neuromuscular transmission. Three days of neostigmine treatment caused a decrease in indirectly and directly elicited muscle contraction. Miniature end-plate potential amplitude and frequency, end-plate potential amplitude, junctional acetylcholine sensitivity and quantal content of nerve-evoked end-plate potentials were also decreased by this treatment. By 22 to 25 days of continued treatment, the decreased rate of transmitter release had returned almost to normal, whereas the alterations of the postsynaptic membrane persisted for as long as 106 days. Alterations were also found in the muscle action potential and in certain passive electrical properties of the extrajunctional muscle membrane. In addition, many of the physiological changes were correlated directly with the morphological changes observed in rats treated similarly. We conclude that neostigmine treatment in rats in therapeutic doses has deleterious effects on neuromuscular physiology and neuromuscular ultrastructure. Although the pattern of these changes is not identical with that seen in rabbit and human myasthenia gravis, the neostigmine treatment used in patients with myasthenia gravis may contribute in part to the neuromuscular alterations observed in this disease.

Acetylcholine↗
PubMed1977

Effects of neostigmine and pyridostigmine at the neuromuscular junction.

The effect of subcutaneous administration of pyridostigmine or neostigmine for 7 to 15 days on neuromuscular transmission has been studied in the rat phrenic nerve-hemidiaphragm preparation. The quantal contents of end-plate potentials at different stimulus rates and the amplitude and frequency of miniature end-plate potentials were compared with those of untreated controls. The rate of release of acetylcholine quanta at high stimulus rates, and the frequency of miniature end-plate potentials, were reduced by pretreatment with both pyridostigmine and neostigmine. Presynaptic effects differed in that the number of quanta released by each nerve impulse at a stimulus rate of 1/sec was not altered by pyridostigmine, but was reduced to 52% of normal by neostigmine. The amplitude of miniature end-plate potentials was reduced to 81% by pretreatment with neostigmine and to 54% by pretreatment with pyridostigmine. The cause appears to be a reduction in the number of acetylcholine receptor sites as a result of disorganisation of the postsynaptic muscle membrane, which may contribute to the muscular weakness associated with the long term use of anticholinesterase agents.

Animals↗