hs-6 and Organophosphate-Poisoning

The present study was performed to assess and compare a therapeutic efficacy of obidoxime, HI-6, BI-6 and HS-6 administered in equimolar doses and combined with atropine in cyclosarin-poisoned mice and rats. It was demonstrated that all the therapeutic regimens tested, were able to decrease the cyclosarin-induced toxicity significantly - at least 1.5 times. Higher therapeutic ratios, almost three times, were achieved in rats in comparison with mice. The highest therapeutic ratio was achieved for therapeutic regimen consisting of HI-6 and atropine in both mice and rats. Obidoxime was the least effective oxime in the treatment of cyclosarin intoxication. The BI-6 oxime was significantly more efficacious than obidoxime (in both mice and rats) and HS-6 (in rats) but its effectiveness did not reach the efficacy of HI-6.

Topics: Animals; Cholinesterase Reactivators; Female; Mice; Obidoxime Chloride; Organophosphate Poisoning; Organophosphorus Compounds; Oximes; Pralidoxime Compounds; Pyridinium Compounds; Rats

Different drug combinations consisting of cholinolytic and a cholinesterase (ChE) reactivator provide greater therapeutic efficacy in acute organophosphorus (OP) poisoning in mice than when used alone. Maximum protection, as determined by a shift of the LD50 for the two OP agents, was observed with the cholinolytic benactyzine. A protection index (P.I.) of 42 was obtained when benactyzine was given along with obidoxime in diisopropylphosphorofluoridate (DFP) intoxication. With the more toxic OP agent soman (o-pinacolylmethylphosphonofluoridate), the same cholinolytic only offered a maximum P.I. of 3.2 when administered with HS-6, another bispyridinium ChE reactivator. This beneficial effect of benactyzine is possibly due to its greater antimuscarinic effect in the central nervous system than atropine or dexetimide.

Topics: Acute Disease; Animals; Benactyzine; Cholinesterase Reactivators; Male; Mice; Obidoxime Chloride; Organophosphate Poisoning; Parasympatholytics; Poisoning; Pralidoxime Compounds

Topics: Animals; Antidotes; Carboxylic Ester Hydrolases; Cholinesterases; Male; Organophosphate Poisoning; Oximes; Pralidoxime Compounds; Pyridinium Compounds; Rats; Rats, Inbred Strains; Soman; Tritolyl Phosphates

Topics: Acetylcholinesterase; Animals; Antidotes; Atropine; Brain; Cholinesterases; Male; Mice; Organophosphate Poisoning; Oximes; Pralidoxime Compounds; Pyridinium Compounds; Soman; Structure-Activity Relationship

Topics: Animals; Antidotes; Female; Hemodynamics; Male; Organophosphate Poisoning; Pralidoxime Compounds; Rats; Rats, Inbred Strains; Soman

The bispyridinium oximes HS6 and HI6 were tested in vitro for their ability to restore neuromuscular function in soman-poisoned tissue, using diaphragm and intercostal muscle of the rat and guinea pig and intercostal muscle of man. It was found that the oxime-mediated recovery of function in both tissues of the rat and guinea pig was composed of direct oxime actions, AChE reactivation and adaptation. In the human intercostal muscle, however, only adaptation was observed. These findings might suggest that HS6 and HI6 may have only limited value in the treatment of soman poisoning in man. However, recovery of function in rodent tissues was consistently greater in the diaphragm than in the intercostal muscle and, since human diaphragm tissue was not included in this study the therapeutic efficacy of these oximes in this tissue remains unknown.

Topics: Aged; Animals; Diaphragm; Guinea Pigs; Humans; In Vitro Techniques; Intercostal Muscles; Male; Middle Aged; Neuromuscular Junction; Organ Specificity; Organophosphate Poisoning; Oximes; Pralidoxime Compounds; Pyridinium Compounds; Rats; Soman; Species Specificity; Synaptic Transmission; Time Factors

Topics: Animals; Atropine; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cholinesterases; Lethal Dose 50; Male; Organophosphate Poisoning; Pralidoxime Compounds; Pyridostigmine Bromide; Rabbits; Soman; Time Factors

Monkeys were exposed to varying doses of soman and given therapy. Therapy consisted of pyridostigmine, clonazepam, atropine and HS-6 or HI-6. Cerebral electrical activity, heart rate, respiration, systemic blood pressure and cholinesterase activity were recorded thoughtout the experiment. The animals in the HS-6 series were divided into 4 groups depending upon the dose of soman; one group received 30 microgram/kg of soman, the second group received 40 microgran/kg. All animals in the HI06 series survived while only one of three monkeys in the fourth group survived. Administration of therapy immediately suppressed all seizure activity and convulsions and the animals appeared awake throughout the experiment. All animals exhibited bradycardia and hypotension following the adminstration of therapy. The cholinesterase activity was depressed after administration of HS-6 therapy. Three of the four monkey that received therapy consisting of HI-6 at a dose of 15 mg/kg survived, while one of two that received HI-6 at a dose of 30 mg/kg survived. The animals that received HI-6 at a dose of 15 mg/kg did not exhibit as severe a decrease in blood pressure as the animals in either the HS-6 series or the monkeys that received HI-6 at 30 mg/kg. In addition, these monkeys were awake and appeared alert throughout the experiment and were up within 4-6 hr post-exposure to soman. The animals that received 30 mg/kg exhibited severe hypotension and did poorly.

Topics: Animals; Atropine; Cholinesterases; Clonazepam; Electroencephalography; Female; Heart Rate; Macaca mulatta; Male; Organophosphate Poisoning; Oximes; Pralidoxime Compounds; Pyridinium Compounds; Pyridostigmine Bromide; Respiration; Soman

Investigations into the therapeutic properties of various combinations of the bispyridinium salts HS-3 and HS-6 and the cholinolytics atropine and benactyzine against soman poisoning in unanesthetized male beagles were performed. In our investigations we observed that: 1. The most effective protection against soman poisoning was attained if both oximes were applied early i.m. 6 min after intoxication together with the cholinolytics. 2. On the basis of clinical symptoms HS-6 proved to have a more intensive therapeutic effect than HS-3 upon early application. 3. If HS-3 was applied early after s.c. intoxication with low concentrations of soman (up to 3 LD50), a significant protection or reactivation effect on serium cholinesterase was measured. 4. When HS-3 was applied at the beginning of convulsions--generally 28 min after s.c. intoxication--it also raised the rate of surviving animals. 5. The maximal blood levels for HS-3 and HS-6 were measured 20-30 min after i.m. injection; the half-life values of HS-3 and HS-6 in plasma were 45-60 min.

Topics: Animals; Antidotes; Aspartate Aminotransferases; Atropine; Benactyzine; Creatine Kinase; Dogs; Drug Administration Schedule; Drug Therapy, Combination; Kinetics; Male; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Soman