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 55 records · Page 3Linked to original sources

PubMed1988

Antagonism of blockade produced by atracurium or vecuronium with low doses of neostigmine.

Neostigmine 1.25 mg or 0.625 mg was used to antagonize neuromuscular blockade produced by either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 in four groups of patients (n = 45) when the first EMG response of the train-of-four (A') had recovered to 10% of control (A). The time for A'/A and the train-of-four ratio (D'/A') to reach 70% was recorded. It was found that, after both atracurium and vecuronium, neostigmine 1.25 mg considerably accelerated recovery and, when compared with previous results, differed little from neostigmine 5.0 mg or 2.5 mg. Neostigmine 0.625 mg also significantly accelerated recovery after atracurium and was comparable to neostigmine 1.25 mg. However, with neostigmine 0.625 mg after vecuronium, recovery of D'/A' (but not A'/A) was little faster than spontaneous. Neostigmine 1.25 mg appears to be almost as effective as neostigmine 5.0 mg or 2.5 mg in antagonizing considerable block (90% depression of twitch height) produced by either atracurium or vecuronium, but neostigmine 0.625 mg is not sufficient, especially after vecuronium.

Adult↗

PubMed1999

Antagonism of vecuronium-induced neuromuscular block in patients pretreated with magnesium sulphate: dose-effect relationship of neostigmine.

We have investigated the dose-effect relationship of neostigmine in antagonizing vecuronium-induced neuromuscular block with and without magnesium sulphate (MgSO4) pretreatment. Neuromuscular block was assessed by electromyography with train-of-four (TOF) stimulation. First, we determined neostigmine-induced recovery in patients pretreated with MgSO4 (group A) or saline (group B) (n = 12 each). The height of T1, 5 min after neostigmine, was 43 (7)% in group A and 65 (6)% in group B (P < 0.01). Respective values after 10 min were 59 (7)% and 83 (5)% (P < 0.01). TOF ratio, 5 min after neostigmine, was 29 (6)% in group A and 29 (5)% in group B. Respective values after 10 min were 38 (11)% and 51 (7)% (P < 0.01). To gain insight into the mechanisms leading to delayed recovery after MgSO4, we calculated assisted recovery, defined as neostigmine-induced recovery minus mean spontaneous recovery. Spontaneous recovery was assessed in another 24 patients. Patients in group C received MgSO4/vecuronium and patients in group D vecuronium only (n = 12 each). Five minutes after neostigmine, assisted recovery was 22 (7)% in the MgSO4 pretreated patients and 28 (6)% in controls (P < 0.05). Ten minutes after neostigmine, values were 24 (7)% and 22 (6)%. Maximum assisted recovery was not influenced by MgSO4 pretreatment (27 (6)% in group A and 32 (6)% in group B) and time to maximum effect was comparable between groups: 6 (4-10) min and 7 (5-8) min, respectively. We conclude that neostigmine-induced recovery was attenuated in patients treated with MgSO4. This was mainly a result of slower spontaneous recovery and not decreased response to neostigmine.

Adult↗

PubMed1997

Phase I human safety assessment of intrathecal neostigmine containing methyl- and propylparabens.

UNLABELLED: Intrathecal (i.t.) neostigmine produces analgesia in humans with acute experimental, postoperative, and chronic pain. The sole manufacturer of the preservative-free neostigmine solution used in the initial clinical studies no longer markets this preparation. Although solutions containing preservatives are generally avoided for i.t. injection, methyl- and propylparabens have not been demonstrated to be toxic. After preclinical toxicity screening in animals and Food and Drug Administration approval, 12 volunteers received i.t. neostigmine 10, 30, or 100 micrograms, containing these preservatives and glucose. This preparation produced dose-dependent analgesia, nausea, weakness, and sedation similar to the preservative-free preparation. I.t. neostigmine increased acetylcholine but not norepinephrine concentrations in cerebrospinal fluid. Although nitric oxide synthesis has been implicated in analgesia from i.t. neostigmine injection in animals, cerebrospinal fluid concentrations of nitrite as a measure of nitric oxide were not increased by i.t. neostigmine in these volunteers. These data support the investigational application of i.t. neostigmine containing methyl- and propylparabens in the concentrations studied. IMPLICATIONS: Because intrathecal injection of neostigmine may be a useful analgesic, we performed a Phase I tolerability and safety study of the commercially available neostigmine formulation in human volunteers and found no evidence of toxicity. These data are important to the clinical use of this new therapy.

Adult↗

PubMed1998

Central and peripheral analgesia mediated by the acetylcholinesterase-inhibitor neostigmine in the rat inflamed knee joint model.

UNLABELLED: Intrinsic cholinergic inhibitory pathways present a key modulating system in pain perception. The use of intrathecal (i.t.) acetylcholinesterase-inhibitors, such as neostigmine, result in analgesia in both preclinical and clinical models. However, whether i.t. neostigmine suppresses tonic persistent pain or has peripheral sites of antinociceptive action has not been determined. Thus, we studied central (i.t.) and peripheral (intraarticular; i.a.) neostigmine in a rat inflamed knee joint model. Inhibition of thermal and mechanical hyperalgesia was assessed over 28 h using a modified Hargreaves box and von Frey hairs, respectively. I.t. neostigmine resulted in a dose-dependent thermal analgesia (50% of maximal effective dose [ED50] 0-4 h: 6.6 microg, 24-28 h: 9.4 microg) and mechanical analgesia (ED50 0-4 h: 3.5 microg, 24-28 h: 4.3 microg). I.t. atropine reversed analgesia by i.t. neostigmine. I.a. neostigmine also resulted in an i.a. atropine reversible dose-dependent increase of thermal analgesia, although it did not exceed 60% of a maximal possible analgesic effect with the largest applied dose (ED50 0-4 h: 76.2 microg, 24-28 h: 140.1 microg). Partial suppression of mechanical hyperalgesia was observed after i.a. neostigmine. We conclude that centrally administered neostigmine modulates thermal and mechanical antinociception in this animal model of inflammatory pain. These data suggest a peripheral site of muscarinic antinociception. IMPLICATIONS: This animal study shows that administration of the acetylcholinesterase-inhibitor neostigmine results in enhanced levels of the endogenous neurotransmitter acetylcholine, which seems to act as one of a group of analgesia-modulating compounds at central and peripheral sites in inflammatory pain.

Analgesics, Non-Narcotic↗

PubMed2002

Caudal neostigmine, bupivacaine, and their combination for postoperative pain management after hypospadias surgery in children.

UNLABELLED: In a randomized, double-blinded study, we examined the analgesic efficacy of caudal neostigmine, bupivacaine, or a mixture of both drugs in 60 children. After the induction of general anesthesia, children were allocated randomly into three groups (n = 20) to receive a caudal injection of either 0.25% bupivacaine 1 mL/kg, with or without neostigmine 2 micro g/kg, or neostigmine 2 micro g/kg in normal saline 1 mL/kg. Intraoperatively, children receiving caudal bupivacaine or a bupivacaine/neostigmine mixture maintained hemodynamic stability, required less inhaled anesthetics, and had a shorter recovery time compared with the caudal neostigmine alone. Postoperatively, the caudal bupivacaine/neostigmine mixture resulted in superior analgesia compared with the other two groups. Recovery to first rescue analgesic times were (mean +/- SD) 22.8 +/- 2.9 h, 8.1 +/- 5.9 h, and 5.2 +/- 2.1 h in the bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.001). In addition, the bupivacaine and neostigmine groups received more doses of paracetamol than the bupivacaine/neostigmine group to maintain adequate analgesia in the first 24 postoperative h. Postoperative vomiting occurred in 25%, 10%, and 30% in the caudal bupivacaine/neostigmine, bupivacaine, and neostigmine groups, respectively (P < 0.01). We conclude that caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. IMPLICATIONS: Caudal neostigmine 2 micro g/kg provides postoperative analgesia comparable to caudal bupivacaine in children undergoing hypospadias repair surgery. Co-administration of the two drugs is associated with extended postoperative analgesia and reduced need for supplementary analgesics.

Acetaminophen↗

PubMed1995

Cardiorespiratory and spinal cord blood flow effects of intrathecal neostigmine methylsulfate, clonidine, and their combination in sheep.

BACKGROUND: Intrathecal neostigmine may produce analgesia by itself and may enhance analgesia from spinal clonidine. Before clinical trials, the spinal cord blood flow effects of these drugs alone and in combination should be examined in animals. METHODS: Conscious, nonpregnant ewes with indwelling vascular and thoracic spinal catheters received intrathecal injection of 0.2 or 2 mg neostigmine, 0.2 mg clonidine, or 2 mg neostigmine plus 0.2 mg clonidine. Mean systemic and pulmonary arterial and central venous pressures, heart rate, and cardiac output were monitored, arterial blood was sampled for blood gas tensions and pH, and spinal cord blood flow was determined by colored microsphere injection before and at 15, 60, and 240 min after spinal study drug injection. RESULTS: Neostigmine alone did not affect cardiorespiratory variables or spinal cord blood flow. Intrathecal clonidine alone decreased systemic arterial and central venous pressures, whereas these effects were not observed with addition of neostigmine. Clonidine or neostigmine alone or the combination of clonidine and neostigmine did not affect spinal cord blood flow. CONCLUSIONS: Intrathecal neostigmine alone or in combination with clonidine does not reduce spinal cord blood flow, an important preclinical toxicity issue. These results provide additional support for initial clinical trials of intrathecal neostigmine for analgesia.

Animals↗

PubMed1999

No enhancement of sensory and motor blockade by neostigmine added to mepivacaine axillary plexus block.

BACKGROUND: Intrathecal neostigmine induces analgesia but also several side effects. Recently, 500 microg neostigmine administered intraarticularly was shown to produce postoperative analgesia without side effects. The authors' goal was to determine whether 500 microg neostigmine added to mepivacaine in axillary plexus block prolongs postoperative analgesia. In addition, they wanted to determine the incidence of side effects in patients undergoing hand surgery. METHODS: Sixty-nine outpatients scheduled for carpal tunnel syndrome repair with axillary plexus block were randomly assigned to one of three groups that received saline solution in the axillary plexus and subcutaneously (group 1), 500 microg neostigmine in the axillary plexus and saline solution subcutaneously (group 2), or saline solution in the axillary plexus and 500 microg neostigmine subcutaneously (group 3). Sensory and motor block in the four hand nerve distributions were assessed every 5 min for 30 min The duration of the sensory and motor blocks were assessed after operation. Side effects were also recorded. RESULTS: Neostigmine had no effect on sensory and motor block in any of the four nerve distributions, nor did it increase the median duration of sensory block (215 min; range, 120-330 min) compared with group 1 (247 min; range, 190-287 min) or group 3 (236 min; range, 160-280 min). Motor block was slightly shorter (P = 0.045) in group 3 (190 min; range, 135-285 min) compared with group 1 (218 min; range, 145257 min) and group 2 (215 min; range, 105-343 min). Gastrointestinal side effects occurred in 30% of patients in both neostigmine groups but not in group 1 (P < 0.05). CONCLUSIONS: This study suggests that 500 microg neostigmine added to mepivacaine in axillary plexus block does not prolong postoperative sensory block, but it does cause a relatively high incidence of side effects. These two findings raise doubts about the use of neostigmine associated with local anesthetics for plexus neural block.

Adult↗

PubMed2001

Antiallodynic effect of intrathecal neostigmine is mediated by spinal nitric oxide in a rat model of diabetic neuropathic pain.

BACKGROUND: Intrathecal administration of acetylcholinesterase inhibitors produces antinociception in both animals and humans, but their effect on diabetic neuropathic pain has not been studied. In the current study, we determined the antiallodynic effect of intrathecal injection of an acetylcholinesterase inhibitor, neostigmine, in a rat model of diabetic neuropathic pain. In addition, since acetylcholine can increase release of nitric oxide in the spinal cord, we studied the role of spinal endogenous nitric oxide in the action of intrathecal neostigmine in diabetic neuropathic pain. METHODS: Rats were rendered diabetic with an intraperitoneal 50-mg/kg injection of streptozotocin. Intrathecal catheters were inserted, with tips in the lumbar intrathecal space. Mechanical allodynia was determined by application of von Frey filaments to the hind paw. We first determined the dose-dependent effect of intrathecal neostigmine on allodynia. The role of spinal nitric oxide in the action of intrathecal neostigmine was then examined through intrathecal treatments with a neuronal nitric oxide synthase inhibitor (TRIM), a nitric oxide scavenger (PTIO), L-arginine, or D-arginine. RESULTS: The diabetic rats developed a sustained tactile allodynia within 4 weeks after streptozotocin injection. Intrathecal injection of 0.1-0.5 microg neostigmine dose-dependently increased the withdrawal threshold in response to application of von Frey filaments. Intrathecal pretreatment with 30 microg TRIM or 30 microg PTIO abolished the antiallodynic effect of intrathecal neostigmine. Furthermore, the inhibitory effect of TRIM on the action of intrathecal neostigmine was reversed by intrathecal injection of 100 microg L-arginine but not D-arginine. CONCLUSIONS: Intrathecal neostigmine produces a profound analgesic effect in a rat model of diabetic neuropathic pain. Spinal endogenous nitric oxide contributes to the analgesic action of intrathecal neostigmine in this rat model of diabetic neuropathic pain.

Analgesics↗

PubMed1988

Reversal of pancuronium. Neuromuscular and cardiovascular effects of a mixture of neostigmine and glycopyrronium.

Moderate to deep (67-99% single twitch depression) pancuronium-induced neuromuscular blockade was antagonised with neostigmine (30 micrograms/kg, 60 micrograms/kg, or 80 micrograms/kg) in combination with glycopyrronium. Twenty-seven patients were reversed from 91%-99% twitch depression. Recovery of the first twitch of a train-of-four to 95% of control twitch took at least 20 minutes with neostigmine 30 micrograms/kg. The higher doses were significantly faster (60 micrograms/kg p less than 0.05, 80 micrograms/kg p less than 0.01) and took 15.8 and 14.8 minutes respectively. Reversal to a train of four ratio of 0.75 was not consistently achieved in under 30 minutes with any dose of neostigmine. Nineteen patients were antagonised from a 67%-80% depression of first twitch and in all but two recovery to 95% of control took under 10 minutes. To achieve a train of four ratio of 0.75 took less than 12.5 minutes except in three patients, two of whom, both given neostigmine 30 micrograms/kg, took longer than 20 minutes. Neostigmine 60 micrograms/kg produced as rapid a degree of antagonism as 80 micrograms/kg. Heart rates after reversal decreased gradually in all groups, although the decrease was initially greater in the low dose neostigmine (30 micrograms/kg) group. A fixed 5:1 ratio of neostigmine and glycopyrronium will usually antagonise a moderate (70%-80%) pancuronium block to a train of four of greater than 75% within 12.5 minutes if at least 60 micrograms/kg of neostigmine is administered. More than 30 minutes may be required for reversal whatever the dose of neostigmine, for antagonism from greater than 90% twitch depression.

Adolescent↗

PubMed1997

Postoperative analgesic effect of intrathecal neostigmine and its influence on spinal anaesthesia.

A clinical trial was conducted to evaluate the postoperative analgesic efficacy and the safety of intrathecal neostigmine in patients undergoing anterior and posterior vaginoplasty under spinal anaesthesia. Thirty-six patients were randomly divided into three groups to receive: normal saline (1 ml), morphine (100 micrograms in 1 ml of saline) or neostigmine (100 micrograms in 1 ml of saline) intrathecally just before a spinal injection of hyperbaric bupivacaine (0.5%, 4 ml). The mean [SD] time to the first analgesic (nonsteroidal anti-inflammatory drug) administration was significantly prolonged by intrathecal neostigmine (10.7 [4.3] h) and morphine (15.3 [3.0] h) compared with saline (4.5 [1.0] h). The three groups also differed in the number of patients requiring subcutaneous morphine to complement the analgesia provided by the intramuscular nonsteroidal anti-inflammatory drugs and the mean [SD] times for their administration: eight patients in the saline group (8.0 [3.8] h), one patient in the morphine group (18 h) and two patients in the neostigmine group (8 and 12.9 h). The morphine and neostigmine groups showed similar analgesic effectiveness. The characteristics of spinal anaesthesia were not modified by intrathecal morphine or neostigmine. Severe nausea and vomiting, sweating and distress during surgery were the most obvious adverse effects of intrathecal neostigmine. On the other hand, less hypotension was observed in the neostigmine group. The usefulness of intrathecal neostigmine as the sole postoperative analgesic may be restricted by the severity of its adverse effects.

Adult↗

PubMed2006

Use of neostigmine in the management of acute postoperative pain and labour pain: a review.

Neostigmine is a parasympathomimetic agent that has been recently investigated for use as an adjunct analgesic agent in the perioperative and peripartum period. A number of studies have investigated the intrathecal, epidural, caudal and intra-articular routes of administration of this agent, as well as the addition of neostigmine to local anaesthetics used for brachial plexus block and intravenous regional anaesthesia. While the intrathecal administration of neostigmine produced useful analgesic effects in the postoperative period in some studies, the high incidence of adverse events, mainly nausea and vomiting, limit the clinical usefulness of this route of administration. Several studies investigated the postoperative analgesic effects of epidural neostigmine using a number of different regimens. Overall, this route of administration appeared to improve postoperative analgesia in most studies without increasing the incidence of adverse events, and merits further research. Neuraxial administration of neostigmine appears to be safe in the obstetric population, with no reported adverse effects in the mother or fetus. While intrathecal administration is limited by a high incidence of nausea and vomiting in this patient population, the epidural route appears more promising and requires further investigation. The addition of neostigmine to caudal local anaesthetics was associated with improved postoperative analgesia in a number of studies. A dose of 2 microg/kg proved to be effective in several studies but was associated with an increased incidence of vomiting in some studies. Intra-articular administration of neostigmine 500microg produced a useful analgesic effect in the postoperative period in several studies and was not associated with an increase in the incidence of adverse effects. Studies investigating the efficacy of adding neostigmine to the local anaesthetics used for brachial plexus block and intravenous regional anaesthesia reported conflicting results. Further studies are required to determine the place of the administration of neostigmine by these routes.

Anesthesia, Conduction↗

PubMed1985

Concentration-dependent effects of neostigmine on the endplate acetylcholine receptor channel complex.

The concentration-dependent actions of neostigmine, a carbamate anticholinesterase agent, were studied on the acetylcholine receptor channel complex in voltage-clamped twitch fibers of costocutaneous muscles of garter snakes. Low concentrations of neostigmine (10(-6) or 10(-5) M) increased miniature endplate current (MEPC) amplitude and the time constant of MEPC decay without changing the relationship between the MEPC decay time constant and membrane potential. Acetylcholine- or carbachol-induced endplate current fluctuation spectra were well fitted by a single Lorentzian curve with a characteristic frequency and single-channel conductance unaltered by low concentrations of neostigmine. Concentrations of neostigmine greater than 5 X 10(-5) M decreased MEPC amplitude and split the decay of MEPCs into two components, one faster and one slower than the control rate. These effects were both voltage and concentration dependent. Spectra of current fluctuations recorded in concentrations greater than or equal to 5 X 10(-5) M neostigmine required two time constants, one faster and one slower than the control. Two component spectra were also obtained with carbachol-induced current fluctuation spectra, indicating that these effects of neostigmine were direct and not a consequence of acetylcholinesterase inhibition. Similar results were also obtained in muscles pretreated with collagenase to remove junctional acetylcholinesterase. The fast and slow time constants obtained from current fluctuation spectra decreased and increased, respectively, with either increases in the concentration of neostigmine or membrane hyperpolarization when analyzed in the same fiber. The effects of neostigmine on channel lifetime were reversible with washing. These results indicate that the effects of neostigmine are concentration dependent. Concentrations greater than 2.5 X 10(-5) M exhibit direct effects on the endplate receptor channel complex which are unrelated to acetylcholinesterase inhibition. These actions include: a prolongation of the gating kinetics of the endplate receptor channel complex, the production of an altered state of the receptor channel complex evidenced by a high frequency component to current fluctuation spectra, and a direct action to block the acetylcholine receptor.

Animals↗

PubMedDate not supplied

Subarachnoid neostigmine potentiation of alpha 2-adrenergic agonist analgesia. Dexmedetomidine versus Clonidine.

BACKGROUND AND OBJECTIVES: Intraspinally administered alpha 2-adrenergic agonists produce analgesia in part by causing spinal acetylcholine and nitric oxide (NO) release. Clonidine-induced analgesia is enhanced by subarachnoid neostigmine and inhibited by N-methyl-L-arginine (NMLA), a blocker of NO synthesis. The authors tested whether dexmedetomidine, an alpha 2-adrenergic agonist with greater intrinsic efficacy than clonidine, would be similarly affected by neostigmine and NMLA. METHODS: Drugs were administered subarachnoid to 22 chronically prepared ewes, and antinociception was determined by a noxious mechanical stimulation. Sheep received subarachnoid saline, neostigmine, or NMLA, followed by cumulative doses of clonidine or dexmedetomidine. Neostigmine was injected either 20 or 60 minutes prior to beginning cumulative dosing with the alpha 2-adrenergic agonist. RESULTS: Both clonidine and dexmedetomidine produced dose-dependent antinociception with similar potency (ED50 was 61 +/- 26 micrograms for clonidine and 65 +/- 24 micrograms dexmedetomidine). Neostigmine pretreatment 20 minutes before dosing potentiated clonidine's dose response (ED50 was reduced to 6.8 +/- 2.3 micrograms), but had no effect on dexmedetomidine (ED50 27 +/- 6.1 micrograms). Neostigmine pretreatment 60 minutes before dosing potentiated both clonidine (ED50 was reduced to 11.8 +/- 5.1 micrograms) or dexmedetomidine (ED50 was reduced to 10 +/- 2.1 micrograms). The NMLA did not affect antinociception from dexmedetomidine. CONCLUSIONS: These data are in agreement with previous hemodynamic studies suggesting that neostigmine has a slow onset of action after subarachnoid administration. That clonidine is potentiated more than dexmedetomidine by neostigmine pretreatment at 20 minutes likely may reflect the lower intrinsic efficacy of clonidine. Alternatively, since acetylcholine can cause NO synthesis, lack of effect of NMLA on dexmedetomidine implies that analgesia from this drug is less reliant on acetylcholine-NO mechanisms than clonidine. The large potentiation observed between neostigmine and these alpha 2-adrenergic agonists carries important clinical implications.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1992

Inhibitions by 6-hydroxydopamine and neostigmine singly or together of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA) and administration of the acetylcholinesterase inhibitor neostigmine, singly or together, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the tissue catecholamine concentration of the gastric wall and the labeling index of the gastric mucosa, were investigated in inbred Wistar rats. Rats received s.c. injections of neostigmine (0.075 mg/kg), and/or i.p. injections of 6-OHDA (42 mg/kg twice within 24 hr, and then 105 mg/kg every 2 weeks from 1 week later) 25 weeks after oral treatment with MNNG. Prolonged administration of 6-OHDA or neostigmine significantly reduced the incidence of gastric cancers by week 52, and in combination they had a significantly greater inhibitory effect. 6-OHDA and/or neostigmine had no influence on the histology of gastric cancers. Administration of 6-OHDA, but not neostigmine, significantly decreased the norepinephrine concentration in the antral portion of the gastric wall. The labeling index of the antral mucosa was decreased significantly by treatment with 6-OHDA or neostigmine, and decreased even more significantly by 6-OHDA plus neostigmine. Our findings indicate that 6-OHDA and neostigmine have protective effects against gastric carcinogenesis and that in combination their effects are additive. These results imply that the activities of the sympathetic and parasympathetic autonomic systems together influence gastric carcinogenesis.

Animals↗

PubMed1984

Antagonism of d-tubocurarine-induced neuromuscular blockade with a mixture of 4-aminopyridine and neostigmine in man.

The antagonistic properties of a mixture of 4-aminopyridine (4-AP) 3 mg X ml-1 and neostigmine 0.2 mg X ml-1 (in three patient groups) administered at 90 per cent d-tubocurarine block were compared with those of plain neostigmine (in three patient groups) in thirty-six patients during thiopentone-fentanyl-nitrous oxide-oxygen anaesthesia. The recovery variables included thumb twitch height, thenar e.m.g. peak-to-peak amplitude, and train-of-four ratio in response to supramaximal ulnar nerve stimulation. In addition, mean arterial pressure, heart rate, apnoea time and time to responsiveness to verbal command after nitrous oxide was turned off at 20 minutes of recovery were examined as circulatory and central nervous system responses to antagonism. The addition of 4-AP 30 mg to neostigmine 2 mg enhanced the recovery of train-of-four ratio from 54.2 +/- 5.2 to 80.2 +/- 5.2 per cent at 20 mins of antagonism (mean +/- SEM; p less than 0.01) while adding 4-AP 45 mg to neostigmine 3 mg increased the train-of-four ratio from 67.7 +/- 2.3 to 92.3 +/- 2.4 per cent (p less than 0.01) when compared with plain neostigmine. No statistically significant difference could be found between the groups in the recovery of twitch height or e.m.g. amplitude. The antagonism of d-tubocurarine block with 4-AP 30 mg plus neostigmine 2 mg was at least as effective as with neostigmine 3-4 mg. Mean arterial pressure increased in the group receiving 45 mg 4-AP plus 3 mg neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1996

Neostigmine decreases heart rate in heart transplant patients.

PURPOSE: This study evaluated the effect of neostigmine on heart rate in cardiac transplant patients. METHODS: Neostigmine (2.5-50 micrograms.kg-1) was administered to ASA 1 or 2 patients with normally innervated hearts (controls), and to patients who had undergone recent (< six months before study) or remote (> six months before study) cardiac transplantation. RESULTS: Baseline heart rate was 66 +/- 3 beats.min-1 in controls (n = 10, mean +/- SEM), which was slower than that observed in recently (95 +/- 4 beats.min-1, n = 15, P < 0.001) and in remotely (88 +/- 3 beats.min-1, n = 16, P < 0.001) transplanted patients. Neostigmine produced a dose-dependent decrease in heart rate in all patients. Controls were the most sensitive to neostigmine, with a 10% decrease in heart rate produced by an estimated dose of 5.0 +/- 1.0 micrograms.kg-1. The recently transplanted group was the least sensitive, with the maximum dose producing only an 8.3 +/- 0.9% reduction. The response to neostigmine of the remotely transplanted patients was variable. The estimated dose to produce a 10% decrease in heart rate in this group was 24 +/- 6 micrograms.kg-1 which was greater than that for controls (P = 0.008). Administration of atropine (1.2 mg) reversed the neostigmine-induced bradycardia in all three groups. Reversal of the bradycardia consisted of a transient peak increase in heart rate in controls to 145 +/- 6% of baseline, a value which was greater than that observed in recent (103 +/- 1%, P < 0.001) and in remote (109 +/- 3%, P < 0.001) transplants. CONCLUSIONS: Neostigmine produces a dose-dependent bradycardia in heart transplant patients. Some remotely transplanted patients may be particularly sensitive to the bradycardic effects of neostigmine.

Cholinesterase Inhibitors↗

PubMed2003

Effects of ketamine on neostigmine-induced contractile and phosphatidylinositol responses of the rat trachea.

PURPOSE: Neostigmine causes airway smooth muscle contraction through the direct stimulation of muscarinic receptors and the activation of phosphatidylinositol (PI) responses. Ketamine attenuates airway smooth muscle contraction. It is not clear whether ketamine attenuates neostigmine-induced airway smooth muscle contraction by inhibiting the PI response. This study was designed to examine the effects of ketamine on neostigmine-induced contractile and PI responses of the rat trachea. METHODS: Thirty male Wistar rats weighing 250-350 g were used. In the experiment on the contractile response, active contraction was induced with 1 microM neostigmine in the presence or absence of ketamine. In the experiment on the phosphatidylinositol response, the trachea slices were incubated with [3H]myo-inositol, 1 microM neostigmine, or 100 microM aluminum fluoride, and ketamine. The formation of [3H]inositol monophosphate (IP1), a degradation product of the phosphatidylinositol response, was measured with a liquid scintillation counter. Statistical significance (P < 0.05) was determined by analysis of variance. RESULTS: Neostigmine 1 microM caused tracheal ring contraction. This contraction was attenuated by ketamine dose-dependently and reached resting tension at 100 microM. Neostigmine- and aluminum fluoride-induced IP1, accumulation was also attenuated by ketamine. CONCLUSION: The results suggest that ketamine attenuates neostigmine-induced contractile responses, at least in part, through the inhibition of phospholipase C coupled with G protein in the PI response.

Aluminum Compounds↗

PubMed1998

Neostigmine competitively inhibited nicotinic acetylcholine receptors in sympathetic neurons.

The present experiment investigates the effect of neostigmine on nicotinic acetylcholine receptors (nAChRs) in the cultured neurons from neonatal rat superior cervical ganglia (SCG). Using whole-cell patch clamp techniques, we found that the amplitudes of the currents induced by 50 microM dimethylphenylpiperazinium (DMPP) were 21.5+/-10.7%, 52.9+/-9.2% and 86.9+/-4.9% depressed at the increased concentrations of neostigmine 100, 200 and 400 microM, respectively. The inhibition of neostigmine decreased gradually with the increased concentration of nicotine from 10 to 160 microM. Lineweaver-Burk's double-reversible plot illustrated that neostigmine blocked neuronal nAChRs in a competitive manner. Hyperpolarization of membrane potential from -40 mV to -100 mV did not significantly influence the blockade of neostigmine. Neostigmine could not accelerate the decay of the DMPP-induced currents, neither evoke any detectable currents in SCG neurons. The results indicate that neostigmine depress neuronal nAChRs in a competitive, concentration-dependent and voltage-independent manner, and can not facilitate desensitization of the receptors. The present data suggest that neostigmine blocks neuronal nAChRs by interacting with the ACh binding sites of the receptors.

Animals↗