Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on 60 of our own cases and on the medical literature the authors discuss the diagnostic, pathophysiological and therapeutic aspects of myasthenia gravis. Myasthenia is suspected in cases of motor weakness of changing intensity, diminishing by rest. The weak muscles are innervated by different peripheral nerves. At the beginning a weakness of upperlid-muscles, external eye muscles and bulbar muscles is particularly frequent. There is no sensory loss or other neurological symptoms. A transitory disappearance of motor weakness after an intravenous dose of Edrophonium (Tensilon) is a typical diagnostic sign. The effect is less evident with eye-muscle weakness. A typical appearance of potentials after repetitive stimulation of peripheral nerves as well as other characteristics in electrophysiological testing of muscles are of high diagnostic value. This allows differentiation from other types of muscle weakness. In the pathogenesis of myasthenia an autoimmune process related to a persistent thymus gland plays an important part. This leads to an ultrastructural change in the postsynaptic membrane of the muscle fibre. The postsynaptic membrane no longer reacts in a normal way to acetylcholine as a transmitter substance at the level of the motor endplate. Therefore the first step in the treatment of myasthenia consists of cholinesterase-inhibitors, specially Neostigmin (Prostigmin) and Pyridostigmin (Mestinon). Thymectomy is advised in all cases of myasthenia with the exception of the pure ocular form and of myasthenia in patients older than 60 years. The thymus gland is practically always persistent or hypertrophic in myasthenia. The suprasternal access is recommended. A thymoma should always be operated upon because of the danger of malignancy. In cases where thymectomy is not performed or not successful and if cholinesterase-inhibitors are not sufficiently efficient, treatment with corticosteroids or ACTH is recommended.
...
PMID:[Pseudoparalytic myasthenia gravis. Diagnostic and therapeutic aspects in 60 separate cases]. 98 76

Pyridostigmine bromide (Pyr), a reversible cholinesterase inhibitor, is currently suggested to be the most effective pretreatment drug against intoxication with potent organophosphates (OP). This investigation was conducted to determine if oral low doses of Pyr would affect performance of a simple visual discrimination task, and further to assess the alterations of motor or motivational function that might underlie the performance deficits in the water-deprived rats. Rats were trained extensively on a successive light-intensity discrimination implemented with the use of a multiple schedule. The multiple schedule consisted of one fixed-ratio (FR-10) and one differential reinforcement of low rates (DRL-10 s) component, which were signalled by the 10-s discriminative stimuli of bright (S+) and dim (S-) houselights, respectively, in simple alternation. The light intensity difference (S-/S+) was about 0.6. Pyr, at doses (3-12 mg/kg), which did not cause overt symptoms, moderately decreased S+ respondings but did not affect S- respondings. The ratio of S+/S- respondings, an index of discrimination performance, was moderately decreased. Over the range of doses evaluated, Pyr also attenuated the corresponding water intake in a dose-dependent manner, but it did not significantly affect locomotor activity. The lowest effective doses of the above affected behaviors were virtually identical (6 mg/kg). These results suggest that the disruptive effects of a single oral low dose of Pyr on the rat operant performance involve motivational dysfunction rather than motor impairment.
...
PMID:Acute effects of oral low doses of pyridostigmine on simple visual discrimination and unconditioned consummatory acts in rats. 153 77

Pyridostigmine bromide, a reversible inhibitor of acetylcholinesterase (AChE), is effectively used as a pre-treatment to organophosphate intoxication. Previous studies have shown that an oral dose of 30 mg twice a day produces a sufficient inhibition of the enzyme activity (20-40%) without causing any significant adverse effect. During the Persian Gulf war pyridostigmine was taken for the first time under a chemical warfare threat. We searched for symptoms and complaints that may be related to the medication. Our survey included 213 soldiers who completed a questionnaire regarding possible symptoms and their severity. AChE inhibition level was compared between groups of soldiers with and without complaints. The most frequent symptoms were nonspecific and included dry mouth, general malaise, fatigue and weakness. Typical effects, such as nausea, abdominal pain, frequent urination and rhinorrhea, were infrequent. The severity of the symptoms was generally mild. The symptoms appeared around 1.6 h after taking the medication and recurred after each intake. No correlation was found between levels of cholinesterase and type or severity of complaints. Anxiety, which accompanies wartime, may have contributed to the appearance of significant symptoms. Further investigations concerning the effects of pyridostigmine ingestion under stressful conditions are warranted.
...
PMID:Survey of symptoms following intake of pyridostigmine during the Persian Gulf war. 175 41

Pyridostigmine bromide (Pyr), the current drug of choice in the management of myasthenia gravis, has been suggested for use in Alzheimer's dementia, and as a prophylactic treatment for intoxication with organophosphate cholinesterase inhibitors. The present study was undertaken to evaluate the dose-response and time-course effects of acute oral administration of Pyr over a broad dose range (3-40 mg/kg) on the lever pressing of rats maintained under a multiple fixed-ratio (FR-20) time-out schedule of reinforcement for water reward. The drug produced a dose-dependent biphasic response depression in the overall rate of FR responding. Low doses of Pyr (less than or equal to 12 mg/kg) that caused no gross signs of toxicity only moderately decreased rates of responding, primarily due to a decrease in response rates. Whereas high doses of Pyr (greater than 24 mg/kg) which produced overt signs of peripheral cholinergic intoxication markedly suppressed overall responding, primarily due to cessation of responding. The lowest effective dose of performance disruption was 6 mg/kg, and the ED50 was calculated as 23.3 (17.9-28.7) mg/kg. The time-course data of performance disruption showed that low doses of Pyr (less than or equal to 12 mg/kg) had an onset latency within 40-80 min and a duration of 20-80 min, whereas high doses (greater than or equal to 24 mg/kg) had an onset latency of 20-40 min and a duration greater than 80 min. These results suggest the recommended human therapeutic or prophylactic regimen of 30-120.mg Pyr, orally taken each 8 hours, might adversely affect behavioral performance.
...
PMID:Acute effects of oral pyridostigmine bromide on conditioned operant performance in rats. 206 91

Five subjects exercised on a cycle ergometer for 30 min at 55% peak oxygen consumption on two occasions in an environmental test chamber (ambient temperature = 29 degrees C; dew point temperature = 10 degrees C). Pyridostigmine bromide (PYR), an acetylcholinesterase (AChE) inhibitor, was ingested (30 mg) approximately 150 min before one experiment, and no drug was administered during the other experiment (control). Red blood cell AChE inhibition averaged 40 (+/- 7)% during PYR treatment. Esophageal temperature (Tes), an eight site-derived mean skin temperature, forearm blood flow (FBF; venous occlusion plethysmography), skin blood flow (SkBF; laser-Doppler velocimetry), and metabolic rate (indirect calorimetry) were measured. SkBF decreased 37% after PYR treatment compared with control (P less than or equal to 0.05). The Tes threshold for initiation of cutaneous vasodilation was 36.8 (+/- 0.3) degrees C for the control treatment and 37.0 (+/- 0.3) degrees C for the PYR treatment (P less than or equal to 0.01). FBF was not significantly different between treatments, whereas heart rate was reduced by 7 and 9 beats/min during rest and exercise, respectively (P less than or equal to 0.01). The increased threshold for initiation of cutaneous vasodilation with AChE inhibition by PYR is compatible with nonthermal modulation of the control of thermoregulation through increased acetylcholine (ACh) accumulation. This could potentiate preganglionic transmission to enhance adrenergic vasoconstrictor tone. One suggested mechanism possible at the neuroeffector junction of the sweat gland may be that accumulated ACh diffusion across the adventitia of adjacent arterioles to muscarinic receptors initiates contraction of the smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Acetylcholinesterase inhibitor, pyridostigmine bromide, reduces skin blood flow in humans. 218 85

Pyridostigmine bromide, a reversible cholinesterase inhibitor, was administered orally (capsule gavage) to beagle dogs (10-15 months of age) of both sexes once daily at 5, 10, or 20 mg/kg for 14 days; every 8 hr at 2 or 5 mg/kg for 28 days; or every 8 hr at 0.05, 0.5, or 2 mg/kg for 3 months as part of its preclinical safety assessment. A small portion of the dogs receiving pyridostigmine for 3 months were allowed an untreated recovery period of an additional 3 months. Daily doses of 10 or 20 mg/kg were lethal to some of the dogs when given for up to 14 days and caused severe intestinal distress, including diarrhea, emesis, and reddened feces in all animals. The cause of death was intestinal intussusception. Signs of systemic toxicity apparent at these doses included hypersalivation and tremors. Similar but less severe effects were produced by 5 mg/kg per day; plasma cholinesterase activities were inhibited by all three doses in a dose-related manner. Signs of toxicity in the 28-day and 3-month studies were generally limited to the gastrointestinal tract and included diarrhea or soft stools and reddened or mucoid-containing stools; these signs appeared to reverse upon discontinuation of the drug. A single dog at 2 mg/kg every 8 hr developed an apparent intussusception. There were no pathological changes in clinical chemistry, hematology, or urinalysis parameters associated with doses of 0.05, 0.5, or 2 mg/kg every 8 hr for up to 3 months, nor were any drug-related lesions observed upon gross necropsy and microscopic evaluation of the major tissues and organs. Red blood cell (RBC) acetylcholinesterase (AChE) activities in the 3-month study were inhibited by approximately 10, 50, and 70% in the 0.05, 0.5, and 2 mg/kg every 8-hr dose groups, respectively, and these degrees of inhibition were maintained throughout the period of treatment. These data suggest that prolonged oral administration of pyridostigmine at doses sufficient to cause profound and sustained inhibition of RBC AChE activity (i.e., as high as 70%) cause mainly local, gastrointestinal distress related to altered intestinal motility. At the extreme, this can be manifested as a life-threatening intestinal intussusception. Systemic anticholinesterase effects (other than enzyme inhibition) were observed only at doses of 2 mg/kg and greater, while local (gastrointestinal) effects and inhibition of RBC AChE were observed at doses as low as 0.05 mg/kg.
...
PMID:Pharmacological and toxicological evaluation of orally administered pyridostigmine in dogs. 230 21

Pyridostigmine bromide is currently the pretreatment of choice for operation in a chemical warfare (CW) environment. Under CW conditions, subjects are exposed to thermal stress caused by CW protective clothing. This investigation was conducted to determine if pyridostigmine affects various physiological and biophysical parameters of human temperature regulation in subjects wearing CW protective clothing. Pyridostigmine was administered orally in a randomized double-blind cross-over study in four doses of 30 mg every 8 h. An average of 33% whole blood cholinesterase inhibition was induced in the pyridostigmine treated group 4 h after ingestion of last tablet. The subjects were exposed to 170 min exercise-heat stress (Tdb = 33 degrees C; rh = 60%) consisting of 60 min in a sitting position and two 50-min walks (1.39 m.s-1, 5% grade) separated by 10 min of rest. Non-evaporative heat exchange was significantly higher, -14.0 and -10.6 W.m-2 (p less than 0.03), for the pyridostigmine-treated subjects. No additional differences were found between treatments in the physiological responses and heat balance parameters at the end of exposure: heart rate (HR) was (mean +/- S.D.) 154 +/- 16 and 151 +/- 24 bpm, rectal temperature (Tre) was 39.0 +/- 0.4 and 38.9 +/- 0.2 degrees C, heat storage over the 2 h of exercise was 62 +/- 15 and 70 +/- 15 W.m-2, and sweat rate was 832 +/- 185 and 748 +/- 52 g.h-1, in the pyridostigmine and placebo treatments, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Heat-exercise performance of pyridostigmine-treated subjects wearing chemical protective clothing. 233 65

Pyridostigmine bromide, a quaternary carbamate, is widely used in treatment of myasthenia gravis and has been suggested for use in prophylaxis against intoxication with irreversible cholinesterase inhibitors. Since there are virtually no anatomical data concerning the neuromuscular toxicity of the drug, this study was undertaken to evaluate the effects of acute and subacute doses of pyridostigmine on the ultrastrucutre of nerve terminals in rat diaphragm neuromuscular junctions (NMJs). Pyridostigmine in a Mestinon-equivalent buffer was administered by single, subcutaneous injection (acute exposure; 10-30 min) or by a subcutaneously implanted Alzet osmotic minipump (subacute exposure; 2, 7 or 14 days). Acute exposure doses ranged from 0.0036 mg/kg to 3.6 mg/kg (0.001-1.0 LD50), while subacute exposure doses ranged from 0.43 to 20 mg of the drug. Both acute and subacute exposures resulted in dose dependent alterations of presynaptic elements in diaphragmatic NMJs, which included disruption of organelles in the axon terminal, regional or total withdrawal of the nerve terminal from postsynaptic junctional folds, and invasion of Schwann cell fingers into the synaptic cleft. These ultrastructural observations suggest that the normal cell-to-cell interactions at diaphramatic NMJs are altered by this "reversible," cholinesterase inhibiting drug.
...
PMID:Ultrastructural effects of pyridostigmine on neuromuscular junctions in rat diaphragm. 371 19

Ocular myasthenia is a special form of general myasthenia gravis characterized by unilateral or bilateral ptosis and eye muscle pareses of distinct variability, depending on the time of day and the state of fatigue of the patient. Most important for diagnosis is the Tensilon test, which can, however, produce negative results. In such cases a combination of the Tensilon test with electromyography is indispensable. In ocular myasthenia there is not always an increase in the antibody titer against acetylcholine receptors in the blood. The treatment of ocular myasthenia is based on the application of cholinesterase inhibitors. The drug of choice is Mestinon; however, the reaction of the eye muscles to this drug is often unsatisfactory. Local application of cholinesterase inhibitors in the form of Eserine, Prostigmin etc. is an additional important therapy. Also in ocular myasthenia the modern treatment with Cortisone (alternate-day therapy with 100 mg Prednisone every second day) has proved very useful. Another possible method of interfering with the immunological systems of myasthenia is immunosuppression with Azathioprin or Cyclophosphamide. The pathognomonic significance of the thymus in the autoimmune process of myasthenia gravis is demonstrated by the good results obtained by thymectomy, which can also be performed successfully in ocular myasthenia, not only in young patients in whom the condition is severe, but also in older patients in whom it is chronic. Often, the therapeutic measures mentioned have to be tested one after another or in combination in order to achieve an optimal therapeutic effect.
...
PMID:[Ocular myasthenia]. 399 98

The neuromuscular junctions from diaphragm, soleus, and extensor digitorum longus (EDL) muscles of male albino rats were assessed for morphological alterations following acute (30-min) and subacute (2-day) exposure to pyridostigmine bromide in Mestinon-equivalent buffer. These muscles were selected to compare the effects of the drug on muscles of different fiber type composition. The diaphragm has approximately equal numbers of type I and type II fibers while the soleus and EDL possess primarily type I and type II fibers, respectively. Pyridostigmine was administered to each acute-exposure animal by a single subcutaneous injection of 0.36 mg/kg pyridostigmine and to each subacute-exposure animal by a subcutaneously implanted osmotic minipump containing 10 mg/ml pyridostigmine. Both treatments resulted in whole blood cholinesterase (ChE) depression of approximately 60-70% as determined by radiometric assay. Control animals received only Mestinon-equivalent buffer. Both acute and subacute exposures resulted in morphological alteration of the neuromuscular junctions (NMJs) of all three muscles, although considerable variation in the extent of damage occurred even within individual NMJs. The most frequently observed presynaptic alterations were mitochondrial damage and partial withdrawal of nerve terminal branches (partial denervation). Post-synaptic changes included occasional rarefaction of mitochondrial matrices and disruption of the myofibrillar organization in small numbers of subjunctional sarcomeres. The data indicate that acute or subacute exposure to pyridostigmine bromide at a whole blood ChE depression of 60-70% results in similar alterations to the NMJs of three muscles with substantially different fiber type compositions. Although the severity of the damage varies from fiber to fiber, the variability appears random and not related to a specific fiber type or dosage regimen.
...
PMID:Neuromuscular toxicity of pyridostigmine bromide in the diaphragm, extensor digitorum longus, and soleus muscles of the rat. 409 93


1 2 3 4 Next >>

---