Effects Of Cyanide On Neural Tissue

Since the previous review, several significant papers further implicating elevated cellular calcium in CN-induced neurotoxicity have appeared.1 Ferger and Krieglstein exposed chick telencephalic neurons to 1 mM NaCN for up to 2 h.46 Increases in Ca i were measured with Fura-2, and viability was estimated by trypan blue exclusion. Elevation of Ca i paralleled neuronal damage.46 On the other hand, insertion into PC12 cells of a herpes simplex vector expressing cDNA for calbindin did not prevent...

Clinical Effects Of Sulfur Mustard

The organs most commonly affected by mustard are the skin, eyes, and airways the organs which mustard contacts directly. After a substantial amount of mustard has been absorbed through the skin or inhaled, the hemopoietic system, gastrointestinal tract, and CNS are also damaged. Mustard may also affect other organs but rarely do these produce clinical effects.4 After an asymptomatic latent period of hours, mustard causes erythema and blisters on the skin. This response ranges in severity from...

Metabolism Of Cyanide

Cyanide Thiocyonate Conversion

In contrast to other chemical warfare agents, CN appears biologically in blood, urine, and expired breath.7 It is actually generated in small amounts in neuronal tissue, and researchers have proposed that CN functions as a neuromodulator similar to nitric oxide.27 Cyanide contrasts with nitric oxide in that it is chemically more stable and is not immediately broken down. Enzymes exist that regulate CN concentrations and two sulfurtransferases, rhodanese and 3-mercaptopyruvate sulfurtransferase,...

Cholinergic Toxicity

Mechanism Ach Hydrolysis Ache

The cholinergic system is the primary target of OP nerve agent intoxication. The cholinergic system consists primarily of synthetic choline acetyltransferase and degradative acetylcholinesterase enzymes for the neurotransmitter acetylcholine and its receptors, muscarinic and nicotinic. Nerve agents inhibit AChE activity resulting in accumulation of excess ACh at vital cholinergic sites, thereby causing toxic manifestations. Nerve gases exert their toxic effects by phosphorylating the serine...

References

Wolthuis, O.L., Benschop, H.P., and Berends, F., Persistence of the anticholinesterase soman in rats antagonism with a non-toxic simulator of this organophosphate, Eur. J. Pharmacol., 69, 379, 1981. 2. Kientz, C.E., Langenberg, J.P., and Brinkman, U.A.Th., Micocolumn liquid chromatog-raphy with thermionic detection of the enantiomers of O-ethyl S-diisopropylaminoethyl methylphosphonothioate VX , J. High Resolut. Chromatogr., 17, 95, 1994. 3. Benschop, H.P., Konings, C.A.G., and De Jong,...

Info

Note Calculated for hydrolysis by 1 ml 0.6 plasma or 0.15 liver homogenate. Source From De Jong, L.P.A., Van Dijk, C., and Benschop, H.P., Biochem. Pharmacol., 37, 2939, 1988. With permission. Note Calculated for hydrolysis by 1 ml 0.6 plasma or 0.15 liver homogenate. Source From De Jong, L.P.A., Van Dijk, C., and Benschop, H.P., Biochem. Pharmacol., 37, 2939, 1988. With permission. three species, such as brain and muscle see Section IX . In contrast with the phos-phofluoridates, the...

Intravenous Toxicokinetics Of Soman And Sarin In Various Species

Initial investigations on the toxicokinetics of nerve agents were performed after intravenous i.v. administration of doses corresponding with multiple LD50 values. This route of administration provides basic toxicokinetic data, which can subsequently be compared with results for more realistic routes of administration, e.g., the subcutaneous s.c. , percutaneous p.c. , and respiratory routes. With gradually improving methods of bioanalysis, the administered doses could be lowered. Nevertheless,...

Neostigmine

Metabolic Pathway Neostigmine

Neostigmine NEO is a reversible cholinesterase inhibitor that was introduced into therapeutics in 1931 due to its stimulant action on the intestinal tract. This quaternary ammonium compound has greater stability and potency compared to physostigmine and pyridostigmine. Neostigmine has been used in the treatment of myasthenia gravis for more than 60 years.153 This drug is widely used in anesthesia to antagonize the effects of muscle relaxants after operative surgery. Early work had shown that...

Physostigmine

Degradazione Furosemide

Physostigmine PHY is one of the oldest drugs, isolated from Calabar beans and successfully used for the treatment of glaucoma in 1864. It gained further prominence due to its use in the clinical trials of Alzheimer's disease. Physostigmine is also a potent prophylactic antidote for organophosphate poisoning. It is a reversible cholinesterase inhibitor and has a short duration of action. Being a tertiary amine structurally, it is lipid soluble and hence crosses the blood-brain barrier readily to...

Contributors

Army Medical Research Institute of Chemical Defense ATTN MCMR-UV-PN Dr. Adler 3100 Ricketts Point Rd. Aberdeen Proving Ground, MD 21010-5400 Program Manager Domestic Preparedness Battelle Memorial Institute 2012 Tollgate Rd., Suite 206 Bel Air, MD 21015 Israel Institute of Biological Research U.S. Army Medical Research Institute of Chemical Defense ATTN MCMR-UV-PB Dr. Baskin 3100 Ricketts Point Rd. Aberdeen Proving Ground, MD 21010-5400 Toxicology TNO Prins Maurits Laboratory 2280AA...