On the development of behavioral tolerance to organophosphates IV: EEG and visual evoked responses

Several earlier studies showed that, in contrast with DFP, repeated injections with soman did not lead to behavioral tolerance in rats. The reason for the difference between the effects of these two organophosphate cholinesterase inhibitors was not clear and a neurophysiological approach was undertaken. Four experiments (A, B, C and D) were...

Therapy of organophosphate poisoning in the rat by direct effects of oximes unrelated to ChE reactivation

Isolated rat diaphragm preparations treated with soman or with the irreversible and oxime resistant cholinesterase (ChE) inhibitor S27 (see Compounds) showed a considerable recovery of neuromuscular transmission (NMT) during incubation with the (bis)pyridinium oximes HI-6, HGG-12, P2S and obidoxime. In the soman-treated preparations this NMT...

The bispyridinium-dioxime HLö-7. A potent reactivator for acetylcholinesterase inhibited by the stereoisomers of tabun and soman

Purification of (+)-tabun was accomplished by treatment with electric eel acetylcholinesterase (AChE) in order to bind contaminating (-)-tabun, the more potent enantiomer with respect of AChE inhibition. Electric eel AChE inhibited with (-)-tabun and with purified (+)-tabun show similar properties in reactivation reactions with oximes (pH 7.5,...

Isolation, anticholinesterase properties, and acute toxicity in mice of the four stereoisomers of the nerve agent soman

The four stereoisomers of the nerve agent pinacolyl methylphosphonofluoridate (soman), designated as C(+)P(+), C(+)P(-), C(-)P(+), and C(-)P(-), have different toxicologic properties due to stereospecific interactions in living organisms. We report the isolation of these stereoisomers with more than 99% optical purity. This result was realized...

GLC-analysis and pharmacokinetics of the four stereoisomers of soman

Chemicals/CAS: soman, 96-64-0; Organophosphorus Compounds; Soman, 96-64-0

Persistence of the anti-cholinesterase soman in rats: Antagonism with a non-toxic simulator of this organophosphate

Anaesthetized, atropinized rats were posioned with 6x LD50 soman (1,2,2-trimethylpropyl methylphosphonofluoridate). Purified acetylcholinesterase, injected i.v. 75 min later, was rapidly inhibited, presumably by soman stored in a 'depot' from which it was gradually released. Existence of a depot is supported by the effect of a soman-simulator (...

The efficacy of some bis-pyridinium oximes as antidotes to soman in isolated muscles of several species including man

Previous results had shown that bis-pyridinium oximes, particularly HI-6 are quite effective therapeutically in soman-poisoned rats and mice in vivo and in the rat diaphragm preparation in vitro. The aim of the present study was to investigate the efficacy of bis-pyridinium oximes on soman-inhibited neuromuscular transmission in muscle...

Antidotes to organophosphate poisoning. 2. Thiadiazole-5-carboxaldoximes

Three new nonquaternary oximes have been evaluated with respect to their antidotal activities against organophosphate poisoning. The oximes 1,2,3-thiadiazole-5-carboxaldoxime (1, pKa = 7.6), 2-methyl-1,3,4-thiadiazole-5-carboxaldoxime (2, pKa = 8.4), and 3-methyl-1,2,4-thiadiazole-5-carboxaldoxime (3, pKa = 7.0) were prepared in yields of 56, 24...

Successful oxime therapy one hour after soman intoxication in the rat

The bisquarternary mono-oxime HI-6, and to a lesser extent HS-6, caused functional recovery of neuromuscular transmission in vivo and in vitro when given 60 min after soman, i.e. when the soman-cholinesterase (AChE) complex is said to be fully 'aged'. Atropinised rats, with the tracheas intubated, received 4 x LD50 soman i.v. and were kept alive...

A comparison of the oximes HS-6 and HI-6 in the therapy of soman intoxication in rodents

The bisquaternary mono-oximes HS-6 and HI-6 may both be considered as potential therapeutic agents for soman intoxication. It has been found that HI-6 was superior to an equal dose of HS-6 in the treatment of soman intoxication in mice and rats. Not only did HI-6 protect against higher levels of soman, but also fewer 'delayed deaths' were seen...

The dependence of the blood level of the oxime HS 6 on the severity of organophosphate poisoning

Atropinised anaesthetised rats were injected i.v. with 4, 6 or 8 x LD50 of the organophosphorous anticholinesterase soman. Subsequent treatment with one dose of HS 6 (100 mg/kg, i.v.) delayed respiratory failure by 1 h or more; a further postponement was obtained when an additional HS 6 infusion was given. At the same infusion rate, HS 6 blood...