Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.
Animals ; Electroencephalography ; Factor Analysis, Statistical ; Physostigmine ; Rats ; Yohimbine

BACKGROUND: Cholinesterase inhibitors (ChEIs) which have been widely used clinically are known to have diverse actions on the neuromuscular synaptic transmissions, suggesting that inhibiting cholinesterase (ChE) might not be their only mode of action. ChEIs interact with the nicotinic acetylcholine receptor (nAChR) macromolecule as a weak agonist, and as a modulator inducing desensitization and blockade at high concentrations. In a previous study, we reported that carbamate ChEIs, Pyridostigmine and Physostigmine could facilitate the ionic influx through nAChRs, when precluding the Ach-hydrolyzing effect of acetylChE (AChE) by applying carbachol as an agonist. The facilitation of the nAChR function was supposed to be achieved by AChE-mediated nAChR modulation and possibly by the up-regulation of nAChRs. METHODS: In this study, we analyzed the effect of irreversible organophosphate ChEI, diisopropylfluorophosphate (DFP) on the function of muscular nAChRs in TE671 cells, quantifying carbachol-induced intracellular 22 Na+ influx through nAChRs, using radioassay. RESULTS: Preincubation of cells with 1 mM DFP at 37 degrees C for 10 min as well as the simultaneous application of carbachol and DFP, decreased the carbachol-induced influx dose-dependently.However, preincubation of cells with 10 micrometer DFP potentiated the influx to 132.5+/-7.4% CPM. Moreover, Najar Tx completely inhibited the potentiated 22 Na + influx. CONCLUSIONS: Organophosphate ChEI can facilitate nAChR functions at low concentrations with a yet discovered mechanism, which is supposed to necessitate cellular metabolism, and be possibly mediated by AChE. The inhibition of DFP on nAChR functions at high concentration is attributable to its remained curare-like actions and direct cellular toxicity.
Carbachol ; Cholinesterase Inhibitors ; Cholinesterases* ; Isoflurophate ; Metabolism ; Physostigmine ; Pyridostigmine Bromide ; Receptors, Nicotinic* ; Up-Regulation

Central anticholinergic syndrome is defined as an absolute or relative reduction in cholinergic activity in the central nervous system and has a wide variety of manifestations. It is associated with almost any drug given during anesthesia, except neuromuscular relaxants, and treated with the cholinesterase inhibitor physostigmine. The diagnosis of central anticholinergic syndrome is often made when symptoms resolve promptly after the administration of physostigmine. We present a case of a central anticholinergic syndrome diagnosed by treatment with physostigmine, in a patient who received closure of patent foramen ovale associated with stroke.
Anesthesia ; Anticholinergic Syndrome* ; Central Nervous System ; Cholinesterases ; Diagnosis ; Foramen Ovale, Patent ; Humans ; Physostigmine ; Stroke

BACKGROUND: Spinal anticholinesterase has been shown to have an antinociceptive action to acute noxious stimuli. The purpose of this study was to determine the effect of intrathecal anticholinesterase on the facilitated state developed after tissue injury evoked by formalin injection. METHODS: Rats were implanted with lumbar intrathecal catheters. For nociceptive test, 50 microliter of 5% formalin solution was injected into the hindpaw. The effect of pretreatment with intrathecal neostigmine, physostigmine and edrophonium, administered 10 min before formalin injection, was observed for 60 min. For the evaluation of the effect of posttreatment with intrathecal anticholinesterase, administered 9 min after formalin injection, the response was observed for 50 min. RESULTS: Formalin injection into the paw resulted in a biphasic incidence of flinching of the injected paw. Intrathecal pretreatment with neostigmine, physostigmine and edrophonium produced a dose- dependent suppression of the flinching during phase 1 and phase 2 on the formalin test. Posttreatment with three intrathecal anticholinesterases reduced the phase 2 flinching response. CONCLUSIONS: Both pretreatment and posttreatment with intrathecal anticholinesterase produced an antinociception on the formalin test. These results point out the usefulness of anticholinesterase to acute nociception and facilitated state.
Animals ; Catheters ; Cholinesterase Inhibitors ; Edrophonium ; Formaldehyde* ; Incidence ; Neostigmine ; Nociception ; Pain Measurement* ; Physostigmine ; Rats*

A 21-year-old woman ingested 1,250 mg of diphenhydramine in a single overdose. Diphenhydramine, a rare ingredient in over-the-counter medication, is used to treat insomnia in Korea. Toxicity is usually limited to anticholinergic symptoms. The standard approach to therapy for the treatment of diphenhydramine overdose is supportive care, including physostigmines and sodium bicarbonates. Here, we review the literature and for the first time report a case of acute diphenhydramine overdosage in Korea, complicated with seizures.
Bicarbonates ; Diphenhydramine ; Female ; Humans ; Korea ; Physostigmine ; Seizures ; Sleep Initiation and Maintenance Disorders ; Sodium ; Young Adult

BACKGROUND: Anticholinesterase drug inhibits acetylcholinesterase(AChE), induce accumulation of acetylcholine(ACh) near cholinergic receptors and cholinergic stimulation. This experiment was performed to study the effects of anticholinesterase drugs on gastric motility and the effect of ethanal on anticholinesterase drug-induced motility change. MATERIALS AND METHODS: After excision of stomach, 2x10mm circular musele strips were made, which were then fixed to the isolated muscle chamber. An isometric tension transducer was used to measure the contraction change of the gastric smooth muscle strips after drug addition. RESULTS: Fenthion, and irreversible anticholinesterase drug, increased ACh induced contraction of gastric smooth muscle strips and PAM, a cholinesterase activator, antagnized this action. Physostigmine, a reversible anticholinesterase drug, also increased the ACh induced contraction. The gastric motility was decreased by PAM. Ethanol, which is known to induce smooth muscle relaxation, inhibited the increase of contraction by fenthion. CONCLUSION: These results indicate that irreversible and reversible anticholinesterase drugs increase gastric motility and antagonized by cholinesterase activating drugs. And when exposed to both ethanol and anticholinesterase drug, gastric motility was decreased by the smooth muscle relaxation effect by ethanal.
Acetaldehyde ; Cholinesterase Inhibitors* ; Cholinesterases ; Ethanol ; Fenthion ; Muscle, Smooth ; Physostigmine ; Receptors, Cholinergic ; Relaxation ; Stomach ; Transducers

We found that the expression and activity of endothelial nitric oxide synthase (eNOS) is increased in the hippocampus during exercise (Moon et al., 2006). However, the upstream regulatory factor on the eNOS expression in the hippocampus during exercise has not been clear. In this study, we investigate the role of acetylcholine (ACh) as a regulatory factor for the eNOS expression and activity in the hippocampus during exercise. The results of the present study demonstrate that voluntary wheel running exercise for two weeks increases the expression and activity eNOS. In addition, choline acetyltransferase (ChAT) immnunoreacitvity within the hippocampus was increased after 2 weeks exercise. We further found that the upregulation of ACh with treatment of physostigmine, a booster of ACh releasing, increase the expression and activity of eNOS in the hippocampus. This present study provides the evidence that the upregulation of eNOS during exercise may be mediated by ACh in the hippocampus.
Acetylcholine ; Choline ; Choline O-Acetyltransferase ; Hippocampus ; Nitric Oxide Synthase Type III ; Physostigmine ; Running ; Up-Regulation

We tried subcutaneous physostigmine 31 times in 24 spinal cord injured patients who had lost ejaculatory capacity. Normal semens were obtained in 4 patients(6.7 %), subnormal semen in 1 patient(4.2 %), a few sperms in 5 patients(20.8 %), and no sperm in 14 patients(58.3%). Sperm appearance rate was 41.7%. Patients with injuries in cervical and upper thoracic levels ejaculated successfully mere frequently than those with injuries in lower thoracic and lumbar levels. The results or T, L1, L2 injured patients were not successful. Side effects included nausea and vomiting (91.7%), dizziness(45.8%) and headache(25.0%), but all patients could tolerate them. Significant adverse effects, particularly autonomic dysreflexia, were not found. Artificial uterine inseminations with sperms induced by subcutaneous physostigmine were performed in 3 cases, and all of these attempts were successful. We have 3 live births. In conclusion, subcutaneous physostigmine for provoking ejaculation in anejaculatory spinal cord injury is cheap, easy to be performed and has no significant side effect.
Autonomic Dysreflexia ; Ejaculation* ; Humans ; Insemination ; Live Birth ; Male ; Nausea ; Physostigmine* ; Semen ; Spermatozoa ; Spinal Cord Injuries* ; Spinal Cord* ; Vomiting

Physostigmine, by inhibiting the acetylcholinesterase, leads to accumulation of acetylcholine and hence to cholinergic stimulation at both peripheral and central receptor sites and facilitates cholinergic transmission. To investigats the effects of physostigmine on excitement, delirium, somnolence, and shivering after halothane anesthesia, physostigmine to experimental group or 0.9% NaCl(1ml) to the control group was administered intravenously by slow injection. No other medication affecting the central nervous system was give. Postoperatively, the difference in the level of sedation, blood pressure, and pulse rate between the experimental group and the control group was observed for 2 hours. Sedation was assessed by and independent observer. The arousal time averaged 23.10+/-18.67min. in the experimental group and averaged 42.38+/-24.97min. in the control group. This study suggests that physostigmine effectively reversed the postoperative somnolence, delirium and excitement due to halothane. There was little difference between the two groups concerning changes of mean arterial pressure and pulse rate during the 2 hours. The results were as follows: 1) When physostigmine was administered intravenously to patients after halothane anesthesia, consclousness rapidly returned. 2) There was no statistical significance in the changes of mean arterial pressure and pulse rate between the experimental group and the control group.
Acetylcholine ; Acetylcholinesterase ; Anesthesia* ; Arousal* ; Arterial Pressure ; Blood Pressure ; Central Nervous System ; Delirium ; Halothane* ; Heart Rate ; Humans ; Physostigmine* ; Shivering

BACKGROUND: In korea the agricultural community widely uses organophosphorous, and organophosphorous poisonings are increasing every year. We compared change in activity of acetylcholinesterase and pseudocholinesterase by organophosphorous and by the interaction of ethanol and organophosphorous. We also compared the effect of reversible anticholinesterase drugs, physostigmine and neostigmine. The object of this study is to investigate the effects of several anticholinesterase drugs and on how ethanol influences the activity of cholinesterase. MATERIALS AND METHODS: Fifteen male university students were randomly selected, and blood samples were taken from the antecubital vein. The acetylcholinesterase in the RBC and the pseudocholinesterase in the serum were extracted and separated. The enzyme activity change was measured by the electrometric method. After adding acetylcholine, the pH change was measured with a pH meter. RESULTS AND CONCLUSION: Our results indicated that reversible anticholinesterase drugs decreased the cholinesterase activity more efficiently than organophosphorous. The acetyl cholinesterase and pseudocholinosterase activity were decreased by ethanol. When ethanol was added, oxime a cholinesterase activator, increased acetylcholinesterase activity but dose not increased pseudocholinesterase activity.
Acetylcholine ; Acetylcholinesterase ; Cholinesterase Inhibitors ; Cholinesterases* ; Ethanol* ; Humans ; Hydrogen-Ion Concentration ; Korea ; Male ; Neostigmine ; Physostigmine ; Poisoning ; Pseudocholinesterase ; Veins