PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Soman”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1988

Retention of soman in rats, guinea-pigs and marmosets: species-dependent effects of the soman simulator, pinacolyl dimethylphosphinate (PDP).

Whether the temporary retention of intact soman in the rat and its subsequent delivery from tissues into the circulation of the blood is also demonstrable in guinea-pigs and marmosets has been investigated as was whether the soman simulator PDP (pinacolyl dimethylphosphinate) prevented this retention. Electric eel AChE, intravenously injected 1.5 h after an intravenous soman intoxication into anaesthetized, atropinized and artificially ventilated guinea-pigs (150 micrograms kg-1 soman), marmoset monkeys (100 micrograms kg-1 soman) and rats (330 and 172.5 micrograms kg-1 soman) lost its activity faster than enzyme injected in non-intoxicated animals. Electric eel AChE incubated in the presence of pectoralis or diaphragm muscle isolated from soman-intoxicated rats, guinea-pigs and marmosets 0.5 or 1.5 h after the intoxication, was progressively inhibited, indicating that those muscles still delivered soman into the incubation medium. In rats, PDP (6.4 mg kg-1 i.v.) pretreatment was effective in preventing inhibition of intravenously injected electric eel AChE 1.5 h after intoxication with a high dose of soman (330 micrograms kg-1). But after intoxication with a low dose (172.5 micrograms kg-1), PDP pretreatment was ineffective in this action, however, it did lead to less soman delivery from muscle tissue isolated 30 min following the 172.5 micrograms kg-1 soman intoxication, suggesting that there was less soman in the tissue. In PDP (6.4 mg kg-1 i.v.)-pretreated marmosets (100 micrograms kg-1 soman) and guinea-pigs (150 micrograms kg-1 soman), to the contrary, the trend was for the injected AChE to be more inhibited, whereas only slightly less soman was delivered from isolated muscle tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1984

Formation of soman (1,2,2-trimethylpropyl methylphosphonofluoridate) via fluoride-induced reactivation of soman-inhibited aliesterase in rat plasma.

After incubation (37 degrees) of rat blood or plasma with the nerve agent soman, (CH3)3C(CH3)C(H)O(CH3)P(O)F (7.7 microM), for 10 min, only a small amount of this organophosphate (7 or 1%, respectively) is left, as determined enzymatically (acetylcholinesterase) and gas chromatographically. Comparison of the results obtained with both analyses shows that this residual soman consists only of its P(-)-isomers. Incubation (25 degrees) at pH 4.8-6.1 of such soman-treated rat blood or plasma with sodium fluoride (2.5 mM) for 0.5 min leads to (i) a substantial increase of the P(-)-soman concentration, and (ii) a (partial) reactivation of the soman-inhibited aliesterase, proportional to the amount of generated P(-)-soman. These results indicate strongly that added fluoride ions regenerate soman by a reversal of the inhibition reaction. From the relationship between percentage of reactivation and increase of soman concentration the aliesterase concentration in rat plasma is calculated as 2.6 microM. Sodium fluoride has a similar effect in blood taken from rats to which soman was administered intravenously. The increase of the P(-)-soman concentration is higher with higher sodium fluoride concentrations and at lower pH values. In accordance with the absence of aliesterase, addition of sodium fluoride does not induce an increase of the P(-)-soman concentration in soman-treated human plasma.

Animals↗
PubMed1993

The influence of soman simulator on reactivation by HI-6 of soman-inhibited acetylcholinesterase in preparations of rat and human skeletal muscle.

The aim of our study was to elucidate the phenomenon called "soman depot". Our investigations were focused on the depot formed in the skeletal muscle and on the effects of 1,2,2-trimethylpropyl dimethylphosphonate (PDP), a reported blocker of soman depot formation. The following questions were addressed: (1) how much of acetylcholinesterase (EC 3.1.1.7, AChE) activity can additionally be recovered by Hagedorn bispiridinium oxime reactivator 2-hydroxyimino-methylpyridinium-1-methyl-4'-carbamoyl-pyridinium-1 '-methylether dichloride monohydrate (HI-6) in the skeletal muscle preparations if they are pretreated by PDP prior to incubation in soman (1,2,2-trimethylpropyl methylphosphonofluoridate)? (2) Is this effect uniform along the muscle fibre or different in the endplate in comparison to the endplate-free region? (3) Is the effect of PDP species specific, i.e. does it differ between rat and human muscle? (4) What are the molecular mechanisms of the effects of PDP? PDP pretreatment increased the reactivation of soman-inhibited AChE by HI-6 in both regions of rat skeletal muscle. This increase was smaller in human skeletal muscle. The PDP-mediated increase in HI-6 reactivation was most efficient in the endplate-rich region of rat diaphragm as demonstrated biochemically and histochemically, but it could not be explained by the blockade of soman depot alone since it was also observed at low soman concentrations, at which soman depot is not supposed to form. This PDP effect could be better explained by the direct interactions of PDP with AChE resulting in decreased AChE phosphorylation. Soman concentration-dependent increase in HI-6 reactivation by PDP, which was more efficient at a high than a low soman concentration and could therefore originate from blockade of soman depot, was observed in the endplate-free region of rat diaphragm. It was also found in human muscle but was again smaller in this species. According to our EPR study, solubilization of soman in the lipophilic cell membrane compartment can be excluded as a mechanism producing significant soman depot. In general, our results suggest a more complex mechanism of PDP action than reported previously.

Acetylcholine↗
PubMed1989

Survivors of soman poisoning: recovery of the soman LD50 to control value in the presence of extensive acetylcholinesterase inhibition.

Initially, mice were pretreated with atropine (17.4 mg/kg; IP) and the oxime reactivator HI-6 (50 mg/kg; IP) 5 min prior to an injection of soman (287 micrograms/kg, SC); approximately 2.1 x LD50 dose). More than 95% of the mice survived this dose of soman with atropine and HI-6 pretreatment. In these survivors of soman poisoning the return of the soman LD50 value to control value (124 micrograms/kg, SC) was determined at various times after the initial soman exposure. Mice which survived exposure to a lethal dose of soman by pretreatment with atropine and HI-6 were sensitized to the lethal effects of soman upon reexposure. The SC soman LD50 at 4 h, after surviving the initial soman exposure, was 20 micrograms/kg. The normal soman LD50 (as evidenced by a LD50 value which was not significantly different from the control value) returned within 4 days, at which time there was still extensive acetylcholinesterase inhibition in all brain regions (striatum, pons-medulla, cerebellum, hypothalamus, hippocampus), diaphragm and erythrocytes. Serum carboxylesterase recovered to control levels within 48 h, whereas liver carboxylesterase activity was not inhibited following the initial soman exposure. The results demonstrate that there is an excess of acetylcholinesterase which is required for normal response in the toxicological sense.

Acetylcholinesterase↗
PubMedDate not supplied

Residual behavioral incapacitation after therapy of soman intoxication: the effect of a soman simulator.

When rats are intoxicated with high doses of the cholinesterase inhibitor soman (5-8 X LD50), the compound is temporarily stored in a "depot" from which it is gradually released. Thus, despite an initially successful therapy with the oxime HI-6 and atropine, the released soman re-intoxicates the organism and death may ensue in several hours. Soman simulators, i.e., non-toxic structural analogues of soman, have been synthesized which are capable of preventing death in soman poisoned rats by modifying the accumulation and release of soman from its depot. Earlier experiments have demonstrated that prophylaxis with the simulator pinacolyl dimethyl phosphinate (PDP) combined with HI-6 and atropine is capable of preventing death in animals heavily poisoned with soman. Moreover, gross observation of successfully treated animals suggested that they were in fairly good condition with respect to general health and neurological functioning. Since the degree of behavioral impairment remaining after soman intoxication and subsequent treatment may be a crucial factor for survival under difficult circumstances, quantitative behavioral experiments were carried out to substantiate these observational findings. Using a recently developed, tv/microprocessor-based system for the measurement of coordinated hindlimb movement in the rat, the residual behavioral effects of successful soman therapy were evaluated. Performance of animals treated with atropine sulphate (25 mg/kg, IP), soman (5 X LD50, IV), HI-6 (56 mg/kg, IV) and the soman simulator PDP was compared to that of animals similarly treated but without additional PDP treatment and to that of saline controls in a series of experiments, varying dose and time of injection of PDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Toxicokinetics of the four stereoisomers of the nerve agent soman in atropinized rats--influence of a soman simulator.

The toxicokinetics of the four stereoisomers of C(+/-)P(+/-)-soman were investigated in anesthetized, atropinized, and artificially ventilated rats at iv doses of 6 (495 micrograms/kg) and 3 LD50. By integration of a thermodesorption/cold trap injector into our GLC analysis, the soman stereoisomers could be followed in rat blood down to a minimum detectable concentration, i.e., 1.5 pg/ml (8.3 pM), 55-fold lower than that published previously. This new detection limit is probably near or below the minimum concentration relevant for survival. Whereas C(+)P(+)-soman disappears in vivo from rat blood within 0.25 min, the toxicokinetics of C(-)P(+)-soman could be described by a two-compartment model, with a biological half-life of 1-1.5 min. The extremely toxic C(+/-)P(-)-isomers could be followed in rat blood for greater than 4 and 2 hr at doses of 6 and 3 LD50, respectively. The toxicokinetics of the P(-)-isomers are best described with a three-compartment model, with terminal half-lives of 40-64 and 16-22 min at doses of 6 and 3 LD50, respectively. Administration of a 13.6-fold molar excess of the soman simulator 1,2,2-trimethylpropyl dimethylphosphinate (PDP) 10 min prior to administration of 6 LD50 of C(+/-)P(+/-)-soman reduces the terminal half-lives of the C(+/-)P(-)-isomers to the values measured at the dose of 3 LD50 without PDP pretreatment. Previous investigations showed that, without PDP pretreatment, rats suffer from endogenous reintoxication 4-6 hr after initially successful therapy, at C(+/-)P(+/)-soman doses greater than or equal to 6 LD50. Both this reintoxication phenomenon due to the presence of toxicologically significant C(+/-)P(-)-soman levels up to 4 hr after intoxication and its antagonism via PDP pretreatment can be understood on the basis of our toxicokinetic measurements. This shows that such investigations can contribute to insight into the toxicology of C(+/-)P(+/-)-soman and to a better treatment of intoxications with this agent.

Animals↗
PubMedDate not supplied

Characterization of soman-binding antibodies raised against soman analogs.

The production of antibodies against the highly toxic organophosphorus compound soman (GD) has been undertaken. Monoclonal antibodies were raised against two structural analogs of soman which served as haptens for immunization. In these soman analogs the chemically active P-F bond of the soman molecule was substituted by a P-OH group (which is ionized to P-O- under physiological conditions) or a P-H bond, creating compounds which we have named GDOH and GDH, respectively. These soman analogs were linked to carrier proteins through a short linker extending from the pinacolyl group. Monoclonal antibodies were selected according to their ability to bind to the immunizing hapten, and their specificities were determined by competitive inhibition assays. Out of total of 103 anti-GDOH antibodies 22 bound soman, whereas no binding was achieved with 62 anti-GDH antibodies. The two groups of monoclonal antibodies differed also in their structural specificity as demonstrated by different reactivities against a variety of soman analogs and substituted derivatives. These studies indicate that in order to achieve further improvement in anti-soman reactivity with protective potential, other groups (which resemble the OH group) have to be substituted for the F atom in the soman molecule.

Animals↗
PubMed1992

Monoclonal antibodies against soman: characterization of soman stereoisomers.

Hybridomas were produced which expressed monoclonal anti-soman antibodies as determined by microtiter enzyme-linked-antibody immunoassay (EIA). Each of these antibodies was titrated using a competitive inhibition enzyme immunoassay (CIEIA) with a variety of test ligands. The ligands used included soman (a racemic mixture), sarin, tabun, and each of the four stereoisomers of soman (C+ P+, C+ P-, C-P+ and C-P-). In all cases the antibodies tested exhibited IC50 values of 10(-4)-5 x 10(-6) M for soman. When sarin or tabun was used as a ligand, the antibodies exhibited no cross reactivity. All of the antibodies cross reacted with the four soman stereoisomers. A second group of hybridomas were produced which expressed monoclonal antibodies against CsPs-soman. These antibodies were used to make preliminary absolute chiral assignments to the four soman stereoisomers.

Animals↗
PubMed1998

Inhalation toxicokinetics of soman stereoisomers in the atropinized guinea pig with nose-only exposure to soman vapor.

The toxicokinetics of the four stereoisomers of the nerve agent C(+/-)P(+/-)-soman were studied in anesthetized, atropinized guinea pigs for nose-only exposure to soman vapor. During exposure the respiratory minute volume (RMV) and respiratory frequency (RF) were monitored. Blood samples were taken for chiral gas chromatographic analysis of the concentrations of nerve agent stereoisomers and for measurement of the progressive inhibition of acetylcholinesterase (AChE). The animals were exposed for 4-8 min to 0.4-0.8 LCt50 of C(+/-)P(+/-)-soman. Concentrations of the P(-)-isomers increased rapidly during exposure, up to several nanograms per milliliter of blood. Mathematical equations describing the concentration-time courses of the P(-)-isomers were obtained by nonlinear regression. The kinetics were mathematically described as a discontinuous process, with a monoexponential equation for the exposure period and a two-exponential equation for the postexposure period. The absorption phase of C(+)P(-)-soman lagged behind that of the C(-)P(-)-isomer, presumably due to preferential covalent binding at as yet unidentified binding sites. The terminal half-life observed after nose-only exposure is longer than that observed after an equitoxic iv bolus administration, which suggests the presence of a depot in the upper respiratory tract from which absorption continues after termination of the exposure. Two types of nonlinearity of the toxicokinetics were observed, i.e., with dose and with exposure time. The AChE activity was rapidly inhibited during exposure to the nerve agent vapor. There were no soman-related effects on RMV and RF. The toxicokinetics of the soman stereoisomers observed for nose-only exposure are compared with those determined for iv bolus and sc administration.

Absorption↗
PubMed1998

Low level nose-only exposure to the nerve agent soman: toxicokinetics of soman stereoisomers and cholinesterase inhibition in atropinized guinea pigs.

In order to initiate a quantitative basis for the toxicology of low level exposure to nerve agents, the toxicokinetics of soman stereoisomers during nose-only exposure for 5 h to 20 ppb (160 microg/m3) of C(+/-)P(+/-)-soman in air were studied in restrained, anesthetized, and atropinized guinea pigs. The concentrations of the toxic C(+/-)P(-)-soman stereoisomers in blood increased according to a biexponential function, after an initial lag time of ca. 30 min for C(+)P(-)-soman, with final concentrations </= 36 pg/ml. It is hypothesized that the lag time is due to binding to carboxylesterases (CaE), partly in the airways prior to systemic uptake. The gradual inhibition of acetylcholinesterase (AChE) in erythrocytes during the exposure appeared to be in satisfactory accordance with the observed levels of the C(+/-)P(-)-soman stereoisomers in blood. Inhibition of AChE in brain and diaphragm is insignificant at the end of the exposure period. This result suggests that neuropsychological disorders are unlikely to develop in this exposure scenario. However, incapacitating miosis due to direct penetration of nerve agent into the eye would probably occur. Our experiments should be reconsidered for exposure of primates, which lack scavenging CaE in their blood. It is argued that the same challenge level in primates might give rise to higher blood levels of C(+/-)P(-)-soman stereoisomers and concomitantly higher inhibition levels of AChE. Therefore, the critical Ct (mg.min/m3) values for nonsystemic effects on eyes and airways and systemic effects might be less divergent than in guinea pigs.

Administration, Inhalation↗
PubMed1985

A method for generating toxic vapors of soman: toxicity of soman by inhalation in rats.

A method for administration of highly toxic chemicals by inhalation was developed. The model has three features of special interest: (1) a diffusion cell for producing a constant gas concentration, if necessary for several hours and days, (2) a small rapidly equilibrated inhalation chamber (1100 ml), and (3) complete isolation of the toxic chemicals from the atmosphere. The LCt50 of the anticholinesterase soman [o-(1,2,2 trimethylpropyl)-methyl-phosphonofluoridate] was 400 mg min/m3, registered 24 hr after the end of exposure. The lethal concentration X time of soman was 520 +/- 60 mg min/m3 when exposing the animals until death in the inhalation chamber. The exposure was less than 30 min and the concentration of soman was 21 mg/m3. The inhibition of acetylcholinesterase, cholinesterase, and carboxylesterase activities in different tissues was analyzed to study the possible barrier mechanisms that might exist in the body to soman. There was a large inhibition of the carboxylesterase and cholinesterase activities in bronchi and lungs as well as in blood. Carboxylesterases were important as detoxifying enzymes, as shown by 70% enhancement in toxicity of soman following sc pretreatment with TOCP (tri-ortho-cresyl-phosphate), a carboxylesterase inhibitor.

Acetylcholinesterase↗
PubMed1978

Successful oxime therapy one hour after soman intoxication in the rat.

The bisquaternary 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 by artificial respiration. 60 min later HI-6 was administered and after an additional 15 min the tracheal tube was removed. Nearly all animals survived for 24 h. After 6 X LD50 soman followed by HI-6, HI-6, respiratory failure was delayed for hours but almost all animals died within 24 h. Against equal doses of soman, HS-6 was less effective. In experiments with isolated rat phrenic nerve-diaphragm preparations, HI-6 given 60 min after soman produced functional recovery which could be abolished by a second dose of soman, suggesting that HI-6 had reactivated the AChE and that this enzyme was then reinhibited by the second dose of soman. HI-6 reactivates purified bovine erythrocyte AChE when added immediately after inhibition by soman, but does not reactivate tabun-inhibited AChE. Accordingly, no functional recovery of neuromuscular transmission was found in rat diaphragm when HI-6 was administered 60 min after tabun. Furthermore, functional recovery was not obtained with HI-6 after exposure diaphragms to S 27, which carries a hydroxyl group instead of an alkoxy group--i.e. it is "pre-aged"--and instantaneously forms an inhibitor--enzyme complex identical to the "age" soman--enzyme complex. These results exclude the possibility that the functional recovery was caused by a direct pharmacological effect of the oxime. The functional recovery of diaphragms treated with II-6 60 min after exposure to soman was not accompanied by a return of histochemically detectable AChE activity. The capacity of the isolated diaphragm to hydrolyze (3H)-acetylcholine, however, seemed to be reactivated to a very small (1--2%) extent by HI-6, 60 min after exposure to soman. It is concluded that soman-inhibited cholinesterase in intact rat tissue "ages" much more slowly than does soman-inhibited purified cholinesterase, so that even after 60 min enough "non-aged" inhibited AChE is still susceptible to reactivation to be lifesaving.

Animals↗
PubMedDate not supplied

Effects of subchronic soman on avoidance-escape behavior and cholinesterase activities.

Male Sprague-Dawley rats were trained on a discriminated avoidance-escape task. They were administered subchronically saline, 12.7 micrograms/kg (0.125 LD50) soman, or 25.5 micrograms/kg (0.25 LD50) soman. Injections were given 5 days per week for 4 weeks. Injections were given subcutaneously immediately following the avoidance behavior test session. Soman produced a reduction in avoidance behavior efficiency in a dose dependent manner. When soman was discontinued, the rats recovered their pre-soman control baselines. Untrained rats given soman according to the same soman regimen were used to measure acetylcholine in brain and cholinesterase activities in brain, blood, and diaphragm. After 18 soman injections at 12.7 and 25.5 micrograms/kg acetylcholine was reduced significantly only in the amygdala. Blood cholinesterase was inhibited as much as 57% after 12.7 micrograms/kg soman and 74% after 25.5 micrograms/kg. Plasma cholinesterase was inhibited to 24% by the 12.7 micrograms/kg dose of soman and to 38% by the 25.5 micrograms/kg dose. Plasma cholinesterase recovered to control levels 11 days after cessation of soman, and whole blood cholinesterase recovered 25 days after cessation of the higher soman dose. Cholinesterase was inhibited significantly in the hippocampus and amygdala in a dose dependent manner. The cholinesterase activities appear to parallel the soman induced decrement in avoidance behavior and the subsequent recovery to control levels following withdrawal of soman.

Animals↗
PubMed2001

Beneficial effects of TCP on soman intoxication in guinea pigs: seizures, brain damage and learning behaviour.

Poisoning with the potent nerve agent soman produces a cascade of central nervous system (CNS) effects characterized by severe convulsions and eventually death. In animals that survive a soman intoxication, lesions in the amygdala, piriform cortex, hippocampus and thalamus can be observed. In order to examine the mechanisms involved in the effects of soman and to evaluate possible curative interventions, a series of behavioural, electrophysiological and neuropathological experiments were carried out in the guinea pig using the NMDA antagonist N-[1-(2-thienyl)cyclohexyl] piperidine (TCP) in conjunction with atropine and pyridostigmine. The NMDA antagonist TCP appeared to be very effective in the treatment of casualties who suffered from soman-induced seizures for 30 min: (i)Seizures were arrested within minutes after the TCP injection, confirmed by quantitative electroencephalogram (EEG), after fast Fourier analysis. Three hours after TCP the quantitative EEGs were completely normal in all frequency bands and remained normal during the entire 3-week intoxication period. The power shift to the lower (delta) frequency bands, indicative for neuropathology and found in control animals intoxicated only by soman, was not observed in the soman-TCP group. (ii)The gross neuropathology found in soman control animals within 48 h after soman was prevented in soman-TCP animals and was still absent in 3-week survivors. Instead, ultrastructural changes were observed, indicative of defense mechanisms of the cell against toxic circumstances. (iii)Twenty-four hours after soman, soman-TCP animals were able to perform in the shuttle box and Morris water maze. The beneficial effects of TCP on the performance in these tests during the 3-week intoxication period were very impressive, notwithstanding (minor) deficits in memory and learning. (iv)The increase in excitability after TCP was confirmed by an increase in the acoustic startle response. Taken together, these results confirmed the involvement of NMDA receptors in the maintenance of soman-induced seizures and the development of brain damage. They underline the current hypothesis that cholinergic mechanisms are responsible for eliciting seizure activity after soman and that, most likely, the subsequent recruitment of other excitatory neurotransmitters and loss of inhibitory control are responsible for the maintenance of seizures and the development of subsequent brain damage.

Animals↗
PubMed1986

Interaction of soman with beta-cyclodextrin.

Of the following neurotoxic agents, pinacolyl methylphosphonofluoridate (soman), isopropyl methylphosphonofluoridate (sarin) and ethyl N,N-dimethylphosphoramidocyanidate (tabun), only soman was inactivated appreciably at pH 7.40 by beta-cyclodextrin. The interaction of soman, a mixture of four stereoisomers designated as C(+)P(-), C(-)P(-), C(+)P(+), and C(-)P(+), with cyclodextrins was revealed by methods based on the irreversible inhibition of acetylcholinesterase (AChE) that is phosphonylated chiefly by P(-)-isomers of racemic soman and continuous titration of fluoride ions released by soman using a fluoride-specific electrode. Soman and beta-cyclodextrin form a 1:1 complex. At pH 7.40 and 25 degrees C the dissociation constant Kd of this complex and the rate constant k2 of cleavage of soman by beta-cyclodextrin are (0.53 +/- 0.05) mM and (5.9 +/- 0.6) X 10(-2) min-1, respectively. The rate constant k2 max for the cleavage of soman by monoionized beta-cyclodextrin has a value of 2.8 X 10(3) min-1 and the second order rate constant k2 max/kd is 5.3 X 10(6) M-1 min-1. Consequently, soman is hydrolyzed about 2500 times faster by the monoanion of beta-cyclodextrin, than by the hydroxide ion. The cleavage of P(-)-soman by beta-cyclodextrin as estimated by AChE inhibition proceeds apparently at the same rate for the C(-)P(-)-and C(+)P(-)-isomers. However, the release of fluoride ions indicated a stereospecific rate of reaction, the P(-)-isomers reacting faster than the P(+)-isomers. At pH 7.40, the inactivation rate of soman by beta-cyclodextrin was as fast in human plasma in vitro as in Tris buffer. This interaction between soman and beta-cyclodextrin, and other data from the literature, suggests that the introduction of catalytic or noncatalytic groups on beta-cyclodextrin might possibly make it a better catalyst for soman inactivation through improvement in the catalytic or in the binding process.

Acetylcholinesterase↗
PubMed1990

Evaluation of several oximes as reactivators of unaged soman-inhibited whole blood acetylcholinesterase in rabbits.

The antidotal benefit of oximes against organophosphorus (OP) anticholinesterase intoxication is thought to be due to reactivation of the OP-inhibited acetylcholinesterase (AChE). This study was conducted to determine whether the antidotal efficacy against soman by the oximes 2-hydroxyiminomethyl-3-methyl-1-[2-(3-methyl-3-nitrobutyl oxymethyl)]-imidazolium Cl (ICD 467) and 1,1'-methylenebis[4-(hydroxyiminomethyl) pyridinium] di-Cl (MMB-4) resulted, in part, from reactivation of the inhibited AChE. These oximes were tested in parallel with pralidoxime Cl (2-PAM) and 1-(2-hydroxyiminomethyl-1-pyridinio-3-(4-carbamoyl-1-pyridinio+ ++)-2-oxapropane di-Cl (HI-6). Rabbits were atropinized (8 mg/kg, i.m.) and intoxicated with soman (13 micrograms/kg, i.v.; 1.2 x LD50) 5 min later. Three minutes after soman, animals were treated with oxime (50, 100 or 150 mumol/kg, i.m.). Whole blood was collected from a catheter in the central artery of the ear just before soman, at 2 min after soman and at 2, 5, 10, 15, 30, and 60 min after oxime or vehicle for determination of AChE activity. Shortly thereafter, animals were anesthetized and exsanguinated with immediate flushing using heparinized saline. AChE activity was also determined on the cortex, medulla-pons and diaphragm to assess central and peripheral reactivation. Treatment with HI-6 or MMB-4 (50 mumol/kg, i.m.) resulted in significant (P less than 0.05) reactivation of soman-inhibited whole blood AChE and diaphragm cholinesterase (ChE), but not brain AChE. In contrast, 2-PAM was completely ineffective in reactivating soman-inhibited AChE. HI-6 was significantly better than MMB-4 in reactivating blood AChE; they were essentially equal against soman-inhibited diaphragm ChE. Three animals exposed to soman and treated with ICD 467 died within 15 min. When animals not exposed to soman were treated with ICD 467 (25 mumol/kg, i.m.), whole blood AChE activity was depressed by 60% within 5-10 min after treatment. Furthermore, ICD 467 failed to reactivate significantly unaged soman-inhibited erythrocyte AChE, in vitro. These observations indicate that ICD 467 would be contraindicated as a therapy for anti-ChE intoxication and that the efficacy of HI-6 or MMB-4 can be explained, in part, by reactivation of soman-inhibited AChE.

Acetylcholinesterase↗