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At least 37 records · Page 2Linked to original sources
PubMed1992

Influence of food on serum ambenonium concentration in patients with myasthenia gravis.

Influence of food on the serum concentration and kinetics ambenonium chloride (AMBC) has been examined in thirteen patients with myasthenia gravis (MG). Mean serum concentrations and Cmax during fasting were higher than those in the non-fasting state. The AUC (0-3 h) was also about four-times larger. The drug effects versus the serum concentration were observed to be anti-clockwise or clockwise. The effective range of the Cmax varied between patients. The unexpected increase in Cmax led to adverse muscarinic actions of AMBC, when the condition was changed from the nonfasting to the fasting state. It is recommended that the dose be changed during non-fasting treatment when adjusting the optimum regimen for patients myasthenia gravis. Patients must be advised to keep to the dosing and dietary schedule in order to avoid unexpected adverse actions to AMBC.

Adult↗
PubMed2005

Similarities between CSF-brain extracellular transfer and neurofibrillary tangle invasion in Alzheimer's disease.

Using the in vivo enzyme protection-enzyme inhibition method, we visualized the distribution of the intraventricularly and cisternally (cisterna magna) injected ambenonium chloride (Am) bound reversibly to the extracellular acetylcholinesterase enzyme (AChE) in the rabbit brain in order to describe the extracellular flow pathways from the cerebrospinal fluid (CSF). We found that the distribution of Am-protected AChE (indicating the Am itself) is similar to tracers having no intracerebral binding sites. The topographical distribution after both ways of application indicates a preferential penetration of Am into the limbic structures of the cerebral hemispheres in a predictable topographic sequence starting from the corticoid areas, allo- and periallo cortices followed by the mesocortical regions and then, in a limited extent, to the isocortex. The lentiform nuclei and the central part of diencephalic halves are inaccessible to Am. The hierarchic order in the sequence of diffusion from the CSF into the hemispheric subpial regions and the distribution pattern of Am resemble the stereotypic topographic expansion pattern and the predominantly limbic distribution of neurofibrillary tangles (NFTs) in Alzheimer's disease and related conditions.

Acetylcholinesterase↗
PubMed1998

Pure red cell aplasia and myasthenia gravis with thymoma: a case report and review of the literature.

A case of pure red cell aplasia (PRCA), myasthenia gravis (MG) and thymoma is reported. A 70-year-old woman presented with severe anemia. She had been diagnosed as having MG 8 years earlier and her symptoms were adequately controlled with ambenonium chloride. When she visited our hospital, her hematocrit was 13.7% with a hemoglobin concentration of 4.7 g/dl and her reticulocyte counts were persistently abnormal at 0.1%. Although both direct and indirect Coombs' tests were positive, there was no evidence of hemolysis. Routine screening tests for other etiologies of anemia were negative. Serological tests for anti-DNA and anti-acetylcholine receptor antibodies gave positive results. A bone marrow examination revealed severe erythroid hypoplasia. PRCA was diagnosed and the patient was treated with periodic transfusions. A lateral view chest roentgenogram and a computed tomography scan of the thorax showed the presence of an anterior mediastinal mass which was suspected to be thymoma. The patient underwent thymothymectomy and the tumor was diagnosed as a thymoma. Although the patient received no treatment for MG and PRCA after surgery, her hematological test results rapidly improved and she was discharged from the hospital on the 29th postoperative day. At that time, her hematocrit was 33.2%, her hemoglobin concentration was 10.0 g/dl, her peripheral reticulocyte level was 1.8% and her left partial ptosis had improved. She is doing well, 9 months after surgery. For a patient to remain in remission without treatment for PRCA and MG after thymothymectomy is extremely rare.

Aged↗
PubMedDate not supplied

[Respiratory form mof myasthenia gravis].

BACKGROUND: Extraocular, facial, bulbar and intercostal muscles are frequently affected in juvenile myasthenia gravis, especially during exacerbations. Acetylcholine receptor antibodies are often present in the blood in this type of myasthenic syndrome. CASE REPORT: A girl presented with an exertional dyspnea at the age of 13 years, that improved after rest. All investigations were negative, except for lung function tests that showed a restrictive pattern. The diagnosis of juvenile myasthenia gravis was finally made at the age of 15 years because of the recurrence of sudden exertional dyspnea and a history of subtle weakness on repetitive movement leading to poor suckling, together with vocal and occasional swallowing difficulties. Dyspnea immediately improved after intravenous injection of 1 mg neostigmine, but the response was transient. No acetylcholine receptor antibody was found and a search for thymoma proved negative. Ambenonium chloride (Mytelase) was effective on clinical exacerbations, but the only improved test after 9 months of treatment was the functional residual capacity. CONCLUSION: Anticholinesterase drugs must be tried in patients who present exertional dyspnea without bronchopulmonary or cardiac disease on the presumption of myasthenia gravis even when ocular or bulbar manifestations are absent.

Adolescent↗
PubMed1991

Pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats.

The pharmacokinetics of ambenonium, a reversible cholinesterase inhibitor, in rats was investigated following intravenous administration of the drug. Mean residence time and steady state volume of distribution were 23-36 min and 0.20-0.311 kg-1, respectively, and were dose independent at the dose of 0.3-3 mumole kg-1. Total body clearance of 8.2 ml min-1 kg-1 over 0.3 mumole kg-1 was slightly increased to 11.3 ml min-1 kg-1 at 3 mumole kg-1. Renal clearance was also increased with the increase of the dose, while hepatobiliary clearance was substantially constant. Ambenonium was highly concentrated in the liver, kidney, spleen, and lung. About 30 per cent of the dose is concentrically stored in the liver at 6 h after administration, and had not disappeared after 24 h.

Ambenonium Chloride↗
PubMed1977

Cholinomimetic teratogens. V. The effect of oximes and related cholinesterase reactivators.

Pyridine-2-aldoxime methiodide and pyridine-2-aldoxime methyl methane sulfonate (P2S) used as supplements to carbachol or neostigmine, greatly lowered the incidence of chicken embryos of vertebral defects and muscular hypoplasia. With 4-pyridine aldoxime the effect of the teratogens was less reduced. Supplementation of carbachol or neostigmine with either ambenonium or toxogonin lessened the occurrence of muscular hypoplasia, but did little, if anything, to prevent malformation of the neck vertebrae. In tests with physostigmine P2S as supplement reduced or prevented cervical defects, but failed to protect the nicotinamide-sensitive parts of the embryo.

Abnormalities, Drug-Induced↗
PubMed1996

Pharmacodynamic analysis of contractile potentiation by cholinesterase inhibitors in rats.

Pharmacological profiles of four cholinesterase (ChE) inhibitors: edrophonium, pyridostigmine, neostigmine, and ambenonium after to administration to rats were analyzed. A pharmacodynamic model was developed by considering acetylcholinesterase (AChE) inhibition, direct antagonism to the nicotinic receptor, and desensitization of the nicotinic receptor. Pharmacokinetics of these drugs are dose-independent and have similar volumes of distribution at steady state (0.4-0.6 L/kg various doses). The t1/2 increases in the order of neostigmine, edrophonium, pyridostigmine, and ambenonium. Inhibitory constants of ChE inhibitors to bovine erythrocyte AChE determined in vitro were 2019, 276, 26, and 3.7 nM for edrophonium, pyridostigmine, neostigmine, and ambenonium, respectively. The effect of ChE inhibitor was monitored as the increase of developed tension of triceps muscle induced by sciatic nerve stimulation. The maximum value of contractile tension after i.v. administration decreased at high doses of each drug and the dose-response curves were biphasic. Time courses of plasma concentration and contractile muscle tension were modeled to estimate the association/dissociation rate constants to AChE and the nicotinic receptor, desensitization rate constant of receptor and the dissociation constant of acetylcholine (ACh) to nicotinic receptor/basal acetylcholine level ratio (Kd/ACh0). The estimated Kd/ACh0 values were not dependent on the drug. A significant correlation between inhibitory constants of ChE inhibitors to AChE estimated by in vivo pharmacodynamic analysis and those determined by an in vitro enzyme kinetic study was shown, while the relationship between dissociation constants to nicotinic receptor estimated by in vivo pharmacodynamic analysis and those measured by an in vitro binding study was not clear. Other process such as desensitisization induced by endogenous ACh diffusion rate of drugs into the synaptic cleft, action of presynaptic receptors, etc., might contribute to the dose-effect relationship of ChE inhibitors.

Ambenonium Chloride↗
PubMed1996

Quaternary nitrogen compounds affect carnitine distribution in rats. Particular emphasis on edrophonium.

Edrophonium (ethyl(m-hydroxyphenyl)dimethylamine) acutely modifies carnitine levels in different rat tissues, increasing hepatic and reducing blood and renal levels. After 2 h edrophonium treatment, the total serum carnitine levels were decreased by 16 (P < 0.001) and 33 (P < 0.001) percent in fed and fasted rats respectively compared to control, and in kidney the levels decreased by 11 (P < 0.05) and 34 (P < 0.001) percent whereas in liver the edrophonium treatment increased the levels by 43 (P < 0.001) and 59 (P < 0.001) percent. The edrophonium action does not depend on the route of administration or on the nutritional state of the animal. Its activity on carnitine levels is neither accompanied by significant variation of serum parameters of carbohydrate, fat and protein metabolism nor of insulin levels. The edrophonium activity is not related to cholinergic action, as physostigmine and ambenonium at concentrations known to increase cholinergic activity do not modify carnitine distribution in tissues. Trimethylphenylammonium (TPA) and trimethyl(p-aminophenyl)ammonium (TPA.NH2), compounds structurally similar to edrophonium, are on the contrary active on levels of carnitine and this effect is not related to their cholinergic potency. In 24 h fasted rats after the TPA and TPA. NH2 treatment, the total serum carnitine levels were decreased by 32 (P < 0.001) and 13 (n.s.) percent respectively compared to control, and in kidney the levels decreased by 15 (P < 0.02) and 5 (n.s.) percent, whereas in liver the treatment increased the levels by 72 (P < 0.001) and 45 (P < 0.01) percent. Moreover atropine, an acetylcholine antagonist, affects carnitine distribution in a way similar to edrophonium. Edrophonium activity on carnitine distribution, probably affects (inter)cellular carnitine transport by direct action on plasma membrane. Effect on capillary endothelium may be responsible for its observed action on muscle contraction force in imminent ischemia.

Ambenonium Chloride↗