Convulsions as the etiology of lactic acidosis in acute isoniazid toxicity in dogs.

The mechanism by which acute isoniazid (INH) overdose causes lactic acidosis is unknown. This study examines the role of convulsion in the development of lactic acidosis in dogs given po lethal doses of INH (75 mg/kg). Following INH, dogs did not develop acidosis until after they had experienced clonic-tonic convulsions. Acidosis, which became more pronounced with successive convulsions, was associated with marked increase of serum lactate (immediate postconvulsive level, 12.3 meq/liter, compared to control of 1.83 meq/liter). Diazepam, 0.5 mg/kg, plus pyridoxine HCl, 150 mg/kg, injected iv immediately following po INH, prevented both convulsions and changes in pH and lactate. When the antidotes were administered after the second convulsion of INH toxicity no further convulsions occurred and blood pH and lactate returned to control levels in 2 hr. “Curarization” of INH-treated dogs prevented both motor seizures and marked increase of lactate. In animals treated with INH and allowed to convulse two times to develop severe acidosis, correction of the acidosis with NaHCO₃ failed to prevent further convulsions and death. Diazepam and pyridoxine combinations, in doses that were ineffective for terminating INH-induced convulsions, became effective when given after correction of acidosis with NaHCO₃. It is concluded that convulsion is the main cause of lactic acidosis in acute INH toxicity and that correction of acidosis does not terminate acute INH toxicity. Although correction of acidosis increases the antidotal effectiveness of diazepam plus pyridoxine, increasing the dose of either or both of these two drugs achieves the same antidotal advantage without the potential problems of metabolic alkalosis which may result from NaHCO₃ administration.     

Evaluation of diazepam and pyridoxine as antidotes to isoniazid intoxication in rats and dogs

Because information regarding efficacious treatment of acute isoniazid (INH) toxicity is incomplete and controversial, diazepam and pyridoxine were investigated as iv antidotes in rats and dogs following administration of po lethal doses of INH. There is a marked species variation in the lethality of INH; the lowest consistently lethal dose is 1500 mg/kg for rats and 75 mg/kg for dogs. Of the two species, the dog more closely approximates man's sensitivity to the lethal effect of INH overdose (80–150 mg/kg). Species variation was also observed in the effects of the antidotes. Diazepam exerted dose-related protection against convulsions in rats; paradoxically, survival was increased by the lowest dose (1 mg/kg) but not by higher doses. In dogs, however, diazepam failed to prevent convulsions but provided dose-related protection against death. Pyridoxine, in rats, did not protect against INH toxicity, but in dogs it showed dose-related effectiveness against convulsions, and all doses (75–300 mg/kg) prevented lethality. Significantly, the highest dose of pyridoxine tested in rats (750 mg/kg) was substantially below the optimal pyridoxine-to-INH antidotal ratio recommended for man (a dose that at least equals the amount of INH ingested), but that dose of pyridoxine would be larger than its LD50 for rats. Combined administration of diazepam with pyridoxine protected against convulsions and death in rats and dogs. Used concurrently, the two antidotes are clearly synergistic for controlling the manifestations of experimental INH overdose. These results have important implications for the management of acute INH intoxication in man.     

Corticosterone increases severity of acute withdrawal from ethanol,pentobarbital, and diazepam in mice

It has been suggested that withdrawal from several subclasses of central nervous system (CNS) depressants involves common underlying mechanisms. For example, mice genetically selected for severe ethanol withdrawal convulsions (Withdrawal Seizure Prone or WSP) have also been found to express severe withdrawal following treatment with barbiturates and benzodiazepines. Corticosteroids appear to modulate severity of withdrawal from CNS depressants. Therefore, it was hypothesized that corticosterone would enhance withdrawal convulsions following acute ethanol, pentobarbital, and diazepam in WSP mice. Corticosterone (20 mg/kg) administered following each of these drugs significantly increased severity of handling-induced convulsions during withdrawal. Corticosterone did not affect pre-withdrawal convulsion scores or handling-induced convulsions of drug-naive mice. These results suggest that withdrawal convulsions following acute ethanol, pentobarbital, and diazepam are sensitive to modulation by corticosterone and they support the hypothesis that stress may increase drug withdrawal severity.Supported by grant # DA05496, #AA06243, and by the Department of Veterans Affairs.     

Acute malathion toxicosis and related enzymatic alterations in Bubalus bubalis: antidotal treatment with atropine, 2-PAM, and diazepam

Oral administration of malathion (MTH) in sublethal (100 mg/kg) or minimal lethal (125 mg/kg) doses in buffalo calves produced toxicity with an onset within 15-20 min and peak effects including severe tremors and convulsions within 40-60 min. Various antidotal drugs were administered alone or in combination at the time of peak malathion toxicity (within 1 h) and were assessed for their ability to alleviate signs of cholinergic toxicity. Blood cholinesterase and aminotransferases activities were monitored at various times. A combination of atropine sulfate (0.5 mg/kg, 1/4 iv and 3/4 im) and pyridine 2-aldoxime methiodide (2-PAM, 20 mg/kg, iv) reversed the clinical evidence of malathion toxicity within 15 min. The combination of atropine sulfate and diazepam (0.75 mg/kg, iv) prevented death and cholinergic signs of toxicity except for weak muscular fasciculations, which persisted for 30-60 min. Atropine sulfate alone was less effective and also did not reverse malathion-induced biochemical changes. In contrast, administration of either 2-PAM (10-30 mg/kg, iv) or diazepam (0.5-1.0 mg/kg, iv) alone accentuated malathion toxicity. Thus, the combination of atropine sulfate and 2-PAM was the most effective antidotal treatment in acute malathion toxicity.     

Treatment of acute isoniazid toxicity.

The clinical symptoms and treatment of acute isoniazid toxicity are presented. The use of supportive measures and chemotherapy are discussed in detail. The pharmacology and biochemistry underlying the symptons of isoniazid poisoning are aslo presented. It is concluded that diazepam in combination with pyridoxine is the treatment of choice for the management of convulsions associated with isoniazid toxicity. Pyridoxine should be administered intravenously in amounts equal to the estimated quantity of isoniazid ingested, even if seizures have not occurred.     

Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism

The effects of selected modulators of GABAergic transmission, either alone or in combination, were tested for their potency on the seizure pattern and mortality induced by convulsant drugs in rat. Pentobarbital and diazepam were effective against both tonic and clonic seizure components induced by bicuculline and picrotoxin. The anticonvulsant profile of ethanol closely resembled that of pentobarbital. Pentobarbital, diazepam and ethanol did not modify seizures induced by strychnine. In contrast, progabide, a central gamma-aminobutyric acid (GABA) receptor agonist, caused significant protection only against convulsions induced by strychnine and its lethality, but did not protect against seizures induced by bicuculline or picrotoxin. Data on interaction of drugs with subprotective doses of these agents clearly demonstrated potentiation of the anticonvulsant actions of these modulators. Thus, seizures induced by bicuculline were more sensitive to the inhibition by pentobarbital in combination with diazepam or ethanol, while pentobarbital with progabide was equally effective against convulsions induced by GABA antagonists. Diazepam, in combination with progabide, blocked only convulsions induced by picrotoxin. Ethanol, in combination with either pentobarbital or with diazepam, was effective against all the three convulsant drugs. These results are consistent with the concept that drugs which facilitate GABAergic transmission are effective against seizures related to an impairment of GABA transmission. Further, the present data indicate that tonic seizures are more susceptible to the actions of drugs than the clonic component. Smaller doses of these drugs, alone or in combination, modified the seizure patterns and mortality, whereas at larger doses, the possible involvement of a nonspecific depressant action cannot be ruled out.     

二巯丙磺钠对氯苯甲脒急性中毒的实验预防

目的：探求动物氯苯甲脒（ 杀虫脒） 急性中毒的更佳解救药剂及方法。方法：通过小鼠、大鼠、家鸽氯苯甲脒急性中毒实验,观察二巯丙磺钠与亚甲蓝单独应用及２ 药联合应用的解毒效果。结果：与对照组相比,二巯丙磺钠对氯苯甲脒急性中毒动物有非常显著的解毒作用（ Ｐ＜ ０ ．０１） , 其解毒效果明显优于亚甲蓝（ Ｐ＜ ０ ．０５） ; 二巯丙磺钠与亚甲蓝联合用药 , 其解毒效果更优于二巯丙磺钠单用（ Ｐ＜ ０ ．０１） 。结论：二巯丙磺钠可望成为氯苯甲脒急性中毒优良的解毒剂,氯苯甲脒急性中毒病人采用二巯丙磺钠联用亚甲蓝可望获得更佳疗效,但忌２药混合后使用或同时从同一途径给药。     

Effect of isoniazid on the pharmacodynamics of cefazolin-induced seizures in rats

Both isoniazid (INH) and cefazolin (CEZ) can have serious adverse effects on the central nervous system (CNS), causing seizures. In this study, we investigated the effect of INH on the pharmacodynamics of CEZ-induced seizures in rats. Male Wistar rats pretreated with INH (150 mg/kg i.p.) or saline received an intravenous infusion of CEZ at 3.2 g/h/rat until the onset of seizures, then samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately. The administration of INH was associated with a reduction in the total dose of CEZ required to produce seizures. The concentrations of CEZ in serum, brain, and CSF in INH-treated rats at the onset of seizures were significantly lower than those in control rats. In rats coadministered with pyridoxine (150 mg/kg s.c.), the concentration of CEZ in CSF at the onset of seizures was significantly higher than that in rats administered INH only. These results suggest that INH potentiates the sensitivity of the CNS to CEZ-induced seizures, and that the increased sensitivity is associated with the inhibition of vitamin B(6) metabolism by INH.     

Seizures induced by theophylline and isoniazid in mice.

Isoniazid-induced seizures respond poorly to anticonvulsants but well to pyridoxine (Vitamin B6); theophylline produces difficult-to-treat seizures with substantial morbidity and mortality. Theophylline therapy depresses plasma pyridoxal-5'-phosphate (PLP), the active metabolite of pyridoxine, suggesting that theophylline-induced seizures might be amenable to treatment with pyridoxine. Our study established the dose-response relationship for convulsions due to isoniazid and theophylline in mice and determined if pyridoxine antagonized such seizures. Female CD-1 outbred mice weighing 25 to 30 g were used. Clonic seizures had clonic activity lasting 5 sec; tonic seizures had loss of the righting reflex with tonic hindlimb extension. Groups of 10 mice received single doses of 50, 100, 150, 200, 250 or 300 mg aminophylline/kg i.p. or 100, 150, 200, 250, 300 or 350 mg isoniazid/kg i.p. and were observed for seizures or death. Pyridoxine or saline with aminophylline or isoniazid were administered simultaneously. The LD50 for aminophylline was 266 mg/kg; for isoniazid it was 160 mg/kg. Doses of 150 mg aminophylline/kg or 100 mg isoniazid/kg did not induce seizures. Pyridoxine with aminophylline or isoniazid did not alter the frequency or time of onset of seizures or death. This was unexpected because pyridoxine antagonizes theophylline-induced seizures in mice and reverses isoniazid-induced seizures in humans. We found no evidence that PLP depletion in mice is a mechanism for seizures induced by isoniazid or aminophylline in a fashion similar to isoniazid in humans.     

The effects of drugs on barbiturate withdrawal convulsions in the rat

The effects of drugs on barbitone withdrawal convulsions in rats have been examined. Morphine and mebanazine had no effect on audiogenically induced barbiturate withdrawal seizures. Alcohol, although suppressing the seizures, did not maintain drug dependence. Chlorpromazine prolonged the recovery period after the induction of the convulsions. Meprobamate, chlordiazepoxide and primidone substituted for the barbiturate and maintained drug dependence. 5-Hydroxytryptamine, when administered intraventricularly, tryptophan, α-methyl-p-tyrosine and ethosuximide reduced the severity of the withdrawal seizures. Reserpine and p-chlorophenylalanine greatly increased the severity of the seizures. Anxiolytic sedatives substituted for barbitone in dependent animals, other drugs studied affected barbiturate withdrawal convulsions in a way similar to other convulsive processes.     

Intravenous injection of flunarizine elicits epileptiform convulsions. Preliminary evaluation of anti-epileptic drugs

The possibility to elicit convulsions in rabbits after flunarizine, iv was investigated. A flunarizine solution, 3.3 mg/ml, was given iv at a rate of 1.5 ml/min in three fractional doses every 30 min. Action of anti-epileptic drugs in seizures induced by flunarizine was additionally examined. Convulsive seizures occurred 2-10 min after the last successive dose of flunarizine as alternating clonic and tonic seizures. A treatment with anti-epileptic drugs showed that both phenobarbital at doses 6, 7 and 7.5 mg/kg iv and pentobarbital at doses of 15, 20 and 25 mg/kg, iv did not entirely suppress convulsive seizures, although convulsive episodes were rare. Diazepam at doses of 1-1.5 mg/kg, iv suppressed convulsive seizures.     

Genetic determinants of severity of acute withdrawal from diazepam in mice: commonality with ethanol and pentobarbital.

Potentially life-threatening seizures can occur following withdrawal from benzodiazepines, ethanol, or barbiturates. In animals, withdrawal severity has been shown to be partially genetically determined for each drug class. Susceptibility to these drugs is partially determined by common genetic factors, but the evidence is conflicting. We tested the hypothesis that acute benzodiazepine withdrawal convulsions are influenced by at least some genes that also affect withdrawal from ethanol and pentobarbital. Results in inbred mouse strains demonstrate that strain susceptibility is genetically correlated with susceptibility to ethanol and pentobarbital. The proportion of variance accounted for by genetic factors common to diazepam and ethanol was estimated at 69%. Results contrast with previous data obtained in mice that were serially tested for withdrawal severity from ethanol, pentobarbital, and then diazepam, because serial testing of mice significantly affected the previous results for some strains. Diazepam withdrawal severity was also genetically correlated with pentobarbital withdrawal. Together, these results suggest that some genes influence severity of withdrawal from several types of depressant drugs.     

Anti-convulsant effects by reduced glutathione and related aminoacids in rats treated with isoniazid

Rats were treated with different doses of isoniazid (INH) causing convulsions. Lethal dose (DL50) and effective convulsant dose (ED50) were calculated. Reduced glutathione (GSH) and related aminoacids were administered to rats receiving INH: the latency and duration of convulsions were recorded; cerebral gamma-aminobutyric acid (GABA) concentrations were determined in rats receiving INH and an association of GSH and INH. GSH and its related aminoacids as cysteine and glycine greatly decreased the duration of INH-induced seizures, while glutamic acid did not protect against convulsions caused by INH. Furthermore, INH causes a decrease in cerebral GABA levels to about half and GSH repeated pretreatment did, however, not prevent the INH induced decline of GABA content: hence, the anticonvulsant effect of GSH can not be ascribed to the restoration of normal levels of anti-epilectically acting GABA, but can be attributed to cysteine and glycine, aminoacids linked to GSH.     

Evaluation of antidotal effects of adamantyl derivative Tamorf in soman poisoning

The nerve agent soman, a powerful inhibitor of acetylcholinesterase (AChE; EC 3.1.1.7), causes an array of toxic effects in the central nervous system. Adamantyl tenocyclidine derivative Tamorf (1-[2-(2-thienyl)-2-adamantyl] morpholine), a compound with potential activity at the N-methyl-D-aspartate (NMDA) receptors and with neuroprotective properties, is effective against convulsions and brain lesions related to soman poisoning. The objective of this study was to evaluate the antidotal potency of Tamorf (2.5 mg kg(-1)), which was tested alone as a pretreatment or in combination with atropine (10.0 mg kg(-1)) as a therapy in rats poisoned with two different sub-lethal doses of soman (1/4 and 1/2 of LD50). The effect of Tamorf was compared with carbamate physostigmine (0.1 mg kg(-1)). The study also determined the possible genotoxic effects of Tamorf and physostigmine, especially primary DNA damage in white blood cells, liver and brain tissue. Tamorf administered 5 min before poisoning stopped soman-induced seizures, was successful against sub-lethal doses of soman and protected AChE activity in the brain (P = 0.0014, P = 0.0019), and in plasma (P = 0.0464, P = 0.0405). Compared with Tamorf, physostigmine was slightly effective in the elimination of soman-induced poisoning in rats. The pharmacological effect of Tamorf and atropine was less effective as therapy, but did not increase soman toxicity (P > 0.05 for all interactions). The results obtained indicate that Tamorf and physostigmine are not genotoxic to rats in the concentrations tested. Treatment with Tamorf seems to be a good alternative for current pretreatment in soman poisoning. Its antidotal mechanism is complex and is based on combined biochemical and receptor properties.     

Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice

In mice, running, clonic and tonic convulsions and lethality were assessed following transcorneal (electroshock) current or convulsant drugs, each administered alone and after cannabidiol (CBD) pretreatment. CBD prevented tonic convulsions caused by a convulsant current (CC) 99.99, and by the convulsant dose (CD) 99.99 values of gamma-aminobutyric acid (GABA) inhibitors, 3-mercaptoproprionic acid (3MPA), picrotoxin (PIC), isonicotinic acid hydrazine (INH), pentylenetetrazol (PTZ) and bicuculline (BIC). Rankorder potencies, based on the antitonic ED50 of CBD, were: 3MPA greater than PIC = current = PTZ = BIC. Further, CBD prevented 3MPA-induced lethality, but failed to prevent the occurrence of the other behavioral endpoints of the above treatments. CBD also failed to prevent convulsions and lethality caused by the CD 99.99 of strychnine, a glycine antagonist. The differential effects of CBD suggest that the cannabinoid acts to inhibit seizure spread in the CNS by an action on GABA, but not glycine, mechanisms.     

A comparison of the efficacy of pyridostigmine alone and the combination of pyridostigmine with anticholinergic drugs as pharmacological pretreatment of tabun-poisoned rats and mice

The ability of two types of pharmacological pretreatment (pyridostigmine alone or pyridostigmine in combination with two anticholinergic drugs) to increase the resistance of rats and mice against tabun and to increase the therapeutic efficacy of common antidotal treatment of tabun-poisoned rats and mice was compared. A significant decrease in the LD50 values of tabun was observed when mice as well as rats were pretreated with the prophylactic antidotal mixture consisting of pyridostigmine, benactyzine and trihexyphenidyle, designated PANPAL. Pyridostigmine-pretreated rats were also more resistant against acute lethal effects of tabun but pyridostigmine-induced resistance of rats was not so high as PANPAL-induced resistance. In addition, the pharmacological pretreatment with pyridostigmine alone was not able to protect mice against tabun-induced acute toxicity. The pharmacological pretreatment with pyridostigmine alone was able to increase the efficacy of currently used antidotal treatment (obidoxime in combination with atropine and diazepam) of tabun-induced poisoning, but PANPAL-induced increase in the efficacy of the same antidotal treatment was significantly higher than an increase induced by pyridostigmine alone. PANPAL-induced increase in the efficacy of antidotal treatment of tabun poisoning was also observed in mice. These findings confirm that PANPAL pretreatment of tabun-poisoned rats and mice seems to be much more suitable than currently used pyridostigmine alone.     

Effect of subacute administration of isoniazid and pyridoxine on lipids in plasma, liver and adipose tissues in the rabbit

The effect of subacute intraperitoneal administration of Isoniazid (INH) on various lipid parameters was studied in liver and adipose tissue in addition to plasma. In the liver, its effect on various phospholipid fractions was also assessed. The changes in lipid profile reflected INH-induced hepatic steatosis. While pyridoxine alone did not alter any of these lipid parameters, its concurrent administration with INH prevented almost all the INH-induced lipid changes. The enhanced lipid mobilization into liver, and a fall in phosphatidylcholine with a concomitant rise in phosphatidylethanolamine in liver impeding lipoprotein synthesis, might be responsible for the hepatic steatosis. Pyridoxal, a pyridoxine metabolite, might have trapped the primary amine functional group of acetylhydrazine and thus prevented the steatosis.     

Protection and reversal by memantine and atropine of carbofuran-induced changes in biomarkers

Male Sprague-Dawley rats injected with a single acute dose of carbofuran (1.5 mg/kg, sc) developed chewing movements and fine tremors within 5–7 min. The signs of maximal severity with hypercholinergic preponderance including muscle fasciculations, convulsions, tracheobronchial secretions, and diarrhea were evident within 15–30 min and lasted for about 2 h. Various antidotal drugs, alone or in combination with atropine sulfate (ATS), were administered as pretreatment or as therapeutic measures to alleviate carbofuran-induced cholinergic toxicity. In fact, pyridine-2-aldoxime methylchloride (2-PAM) or diazepam alone or in combination with ATS did not provide any beneficial antidotal effects. Combined pretreatment with memantine (MEM, 18 mg/kg, sc) and ATS (16 mg/kg, sc) provided complete protection against carbofuran toxicity and reversal of clinical evidence when given therapeutically. Carbofuran intoxication caused significant alterations in the activities of biomarker enzymes such as creatine kinase (CK) and lactic dehydrogenase (LDH) and their isoenzymes patterns in serum as a result of their leakage from the target organs (brain, muscles, and heart). Significant increases in the levels of transaminases (GOT and GPT) and glucose were also noted, MEM in the aforementioned parameters, in addition to similar protective effects reported on target enzyme acetylcholinesterase (AChE). These results, along with those reported previously, indicate that MEM antagonizes carbamates toxicity by maintaining cell membrane permeability and integrity through multiple mechanisms, in addition to muscarinic receptor blocking effect of ATS. © 1993 Wiley-Liss, Inc.     

Effect of cytochrome P450 inhibitors and anticonvulsants on the acute toxicity of acrylonitrile

Some of the more striking expressions of toxicity are the tremors and seizures observed approximately 100 min after exposure of rats to an acutely toxic dose of acrylonitrile (AN). These early events are followed by a second wave of severe clonic convulsions that occur just prior to death at about 3–4 h. For AN, at least two chemical entities could produce these toxic effects, namely the parent AN molecule, the metabolically-released cyanide, or both. Which of these two agents is responsible for each of the symptoms of acute intoxication is not known. To help dissect the toxicity, it was anticipated that an effective inhibitor of the oxidative metabolism of AN to cyanide could help us to understand which toxic symptoms might be associated with each agent. Three inhibitors of oxidative metabolism were tested, namely SKF-525A, 1-benzylimidazole and metyrapone and one alternative substrate, ethanol. As compared to SKF-525A and metyrapone, both 1-benzylimidazole and ethanol were highly effective in reducing blood cyanide levels to insignificant levels in rats treated with an LD90 dose of AN. In addition, both agents abolished the early seizure activity, suggesting that this first phase of seizures is due to cyanide and not the parent molecule. 1-Benzylimidazole did not prevent the severe clonic convulsive phase preceding death, suggesting that these terminal convulsions are due to the toxic effects of the parent AN molecule. The CNS depressant ethanol was only partially effective in attenuating the terminal convulsions. None of these agents affected the incidence of AN-induced mortality, clearly establishing that, even in the absence of cyanide, the parent AN molecule is acutely toxic. The partial effectiveness of ethanol suggested that anticonvulsants might be of benefit. Both phenobarbital and phenytoin protected rats from both the early and terminal convulsions, while valproic acid was ineffective. These effects were not related to a reduction in blood cyanide levels but rather due to their inherent anticonvulsant activity.     

Magnesium sulfate treatment against sarin poisoning: dissociation between overt convulsions and recorded cortical seizure activity

Sarin, a potent organophosphate cholinesterase inhibitor, induces an array of toxic effects including convulsions. Many antidotal treatments contain anticonvulsants to block seizure activity and the ensuing brain damage. Magnesium sulfate (MGS) is used to suppress eclamptic seizures in pregnant women with hypertension and was shown to block kainate-induced convulsions. Magnesium sulfate was evaluated herein as an anticonvulsant against sarin poisoning and its efficacy was compared with the potent anticonvulsants midazolam (MDZ) and caramiphen (CRM). Rats were exposed to a convulsant dose of sarin (96 μg/kg, im) and 1 min later treated with the oxime TMB4 and atropine to increase survival. Five minutes after initiation of convulsions, MGS, CRM, or MDZ were administered. Attenuation of tonic–clonic convulsions was observed following all these treatments. However, radio-telemetric electro-corticography (ECoG) monitoring demonstrated sustained seizure activity in MGS-injected animals while this activity was completely blocked by MDZ and CRM. This disrupted brain activity was associated with marked increase in brain translocator protein levels, a marker for brain damage, measured 1 week following exposure. Additionally, histopathological analyses of MGS-treated group showed typical sarin-induced brain injury excluding the hippocampus that was partially protected. Our results clearly show that MGS demonstrated misleading features as an anticonvulsant against sarin-induced seizures. This stems from the dissociation observed between overt convulsions and seizure activity. Thus, the presence or absence of motor convulsions may be an unreliable indicator in the assessment of clinical status and in directing adequate antidotal treatments following exposure to nerve agents in battle field or terror attacks.