trimedoxime-bromide and Poisoning

The potency of bispyridinium acetylcholinesterase reactivator KR-22934 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with the oxime K203 and commonly used oximes. Studies determining percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of KR-22934 was slightly higher than the reactivating efficacy of K203 and roughly corresponded to the reactivating efficacy of obidoxime and trimedoxime in blood and diaphragm. On the other hand, the oxime KR-22934 was not able to reactivate tabun-inhibited acetylcholinesterase in the brain. The therapeutic efficacy of all oximes studied approximately corresponded to their reactivating efficacy. Based on the results, one can conclude that the oxime KR-22934 is not suitable for the replacement of commonly used oximes for the antidotal treatment of tabun poisoning in spite of its potency to reactivate tabun-inhibited acetylcholinesterase in the peripheral compartment (blood, diaphragm).

Topics: Acetylcholinesterase; Animals; Antidotes; Cholinesterase Inhibitors; Cholinesterase Reactivators; Male; Mice; Obidoxime Chloride; Organophosphates; Oximes; Poisoning; Pyridinium Compounds; Rats; Rats, Wistar; Trimedoxime

The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, trimedoxime, and HI-6) to counteract tabun or cyclosarin-induced acute toxic effects was studied in mice. The therapeutic efficacy of trimedoxime and both newly developed oximes (K074, K075) was significantly higher than the potency of obidoxime and the oxime HI-6 in the case of acute tabun poisonings. On the other hand, the oxime HI-6 was significantly more efficacious than other studied oximes when mice were intoxicated with cyclosarin. The findings support the hypothesis that the therapeutic efficacy of oximes depends on the type of nerve agent. Due to their therapeutic efficacy, both newly developed K oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisonings, while the oxime HI-6 is still the most promising oxime for the treatment of acute cyclosarin poisonings due to its high potency to counteract cyclosarin-induced acute toxic effects.

Topics: Animals; Antidotes; Atropine; Butanes; Cholinesterase Inhibitors; Cholinesterase Reactivators; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Lethal Dose 50; Male; Mice; Muscarinic Antagonists; Obidoxime Chloride; Organophosphate Poisoning; Organophosphates; Organophosphorus Compounds; Oximes; Poisoning; Pyridinium Compounds; Trimedoxime

The clinical effects of self injections of atropine-trimedoxime auto-injectors distributed to the civilian population as a field antidote for nerve agent attack were assessed.. Data on self injections by adults (> or = 18 years) were collected from the Israel Poison Information Center and a hospital Emergency Department's records during a 2-year period. The data included demographics, time interval from injection, type of auto-injector, clinical manifestations and atropinization score.. Sixty-five patients, all with unintentional self injections, were reported. Systemic atropine effects were observed in 24 patients, but no severe atropinization. The atropinization score was significantly higher in the 2 mg atropine dose group than in the two lower dose groups, which were in the normal range. No specific adverse effects attributable to trimedoxime were observed. Intravenous fluids and physostigmine were not required.. Only mild reactions were observed following self-injection of atropine trimedoxime auto-injectors in adults, attesting to their relative safety under these conditions.

Topics: Accidents; Adult; Antidotes; Atropine; Drug Combinations; Humans; Injections; Israel; Poisoning; Self Medication; Trimedoxime

To describe the effects of combined trimedoxime (TMB4) and atropine poisoning from automatic injectors (AI) in children.. Data was collected from two sources: calls to the Israel Poison Information Center (IPIC) during a 1-year period and a cohort of children who presented to pediatric emergency departments (EDs) after unintentional injection of an AI. Demographic data and data regarding the type of AI, site and time of injection, and the clinical manifestations were abstracted.. Data were available for 142 patients. The median age was 8.5 years (range 1.25-18 years). The dose of atropine and TMB4 was higher than the recommended dose for age in 22 (15.5%) cases. There were few side effects attributable to atropine: dilated pupils (26.7%), dryness of mucous membranes (24.6%), and tachycardia (22.5%). Compared with children injected with an age-appropriate dose, children injected with an AI that contained a dose that exceeds the recommended one were more likely to be symptomatic ( P = .029). There were no side effects characteristic to oximes, and no specific medical intervention was required.. Unintentional pediatric atropine and TMB4 injection, even an adult dose in a small child, does not cause significant side effects.

Topics: Adolescent; Antidotes; Atropine; Child; Child, Preschool; Drug Therapy, Combination; Female; Humans; Infant; Injections; Male; Muscarinic Antagonists; Poisoning; Trimedoxime

Topics: Animals; Antibody Formation; Antibody-Producing Cells; Cholinesterase Reactivators; Cytotoxicity, Immunologic; Dichlorvos; Immune System; Insecticides; Male; Mice; Mice, Inbred CBA; Poisoning; Rats; Rats, Wistar; Spleen; Thymus Gland; Trimedoxime

The efficacy of a number of drug pretreatment combinations in protecting mice against lethal effects of soman was determined. Pyridostigmine peroral pretreatment followed by intramuscular postpoisoning therapy with atropine, obidoxime and/or trimedoxime, and diazepam protected mice against the lethal action of soman. Combination of pyridostigmine with trihexyphenidyl, benactyzine and bis-(4-hydroxyiminomethyl) pyridinium-methane dichloride improved prophylactic action even further.

Topics: Animals; Atropine; Diazepam; Female; Male; Mice; Obidoxime Chloride; Poisoning; Pyridostigmine Bromide; Soman; Trihexyphenidyl; Trimedoxime

1. The dispositions of the acetylcholinesterase reactivators: 2PAM-I, TMB4 and R665, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. 2. For all three compounds, radioactivity was eliminated mostly in the urine (60-90% dose in 24 h). Faecal elimination was low (5.8-17.2% in 72 h). 3. All three compounds concentrated in kidney, but only 2PAM-I and R665 concentrated in liver. TMB4 and R665 concentrated in mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Other tissues were weakly and uniformly labelled. Soman poisoning does not modify the kinetic parameters of both compounds, but A4 poisoning increases 2PAM-I tissue concentration. 4. Chromatography of urine and plasma showed only unchanged 2PAM-I, TMB4 and R665 in both healthy and poisoned animals. Despite the high concentration of 2PAM-I and R665 in liver, these oximes are not metabolized.

Topics: Acetylcholinesterase; Animals; Carbon Radioisotopes; Cholinesterase Reactivators; Male; Organophosphate Poisoning; Oximes; Poisoning; Pralidoxime Compounds; Rats; Rats, Inbred Strains; Tissue Distribution; Trimedoxime

A single application of a mixture of cholinolytic and reactivator of cholinesterase (TMB-4 compos. SPOFA) administered intravenously in the dose of 10.0 mg of trimedoxim per kg of live weight to sheep for 60 minutes after an intramuscular intoxication with O-ethyl S-(2-dimethylaminoethyl) methyl phosphonothioate (EDMM) in the dose of 0.00835 mg per kg of live weight (i.m. LD50, 2h) produces an immediate clinical effect. The reactivation of the erythrocytary acetyl cholinesterase (AChE, E.C.3.1.1.7.) examined in 15 minutes after the administration of the antidotal mixture is almost 100 p.c., the reactivation of the plasmatic butyryl cholin esterase (ChE, E.C.3.1.1.8.) approx. from 70 to 80 p. c. Restitution ad integrum occurred not later than in 14 days after the intoxication.

Topics: Animals; Antidotes; Cholinesterase Inhibitors; Cholinesterase Reactivators; Organothiophosphorus Compounds; Oximes; Poisoning; Sheep; Sheep Diseases; Trimedoxime

In a model of sheep perorally intoxicated with a 200.0 mg kg-1 trichlorphon dose, the effectivity of the worked out therapeutical procedure was confirmed; the procedure consisted in the administration of an anticholinergic (20.0 mg of 1.1% atropine s. c. pro toto) and cholinesterase reactivator (30.0 mg of 10% trimedoxime kg-1 i. m.) mixture 4 hours after the administration of the noxious agent. A determination of the erythrocytic acetylcholinesterase (AChE, E.C.3.1.1.7.) and plasmatic butyrylcholinesterase (BChE, E.C.3.1.1.8.) activities in the intoxicated sheep should be considered a decisive clinical and diagnostical test for taking veterinary-therapeutical, veterinary-hygienical or veterinary-sanitary measures in intoxications with anti-cholinesterase substances on the whole.

Topics: Acetylcholinesterase; Animals; Antidotes; Atropine; Butyrylcholinesterase; Poisoning; Sheep; Sheep Diseases; Trichlorfon; Trimedoxime