pralidoxime and anatoxin-a

The prophylactic and neuroprotective impact of a transdermal patch containing eserine and pralidoxime chloride (2-PAM) against (±)-Anatoxin A poisoning was investigated using Wistar strain albino rats. Rats were smooth-shaved on the dorsal side, attached with a drug-in-adhesive matrix type prophylactic transdermal patch for 72 h and challenged with subcutaneous injection of three doses (1.0, 1.5 and 2.0×LD50) of (±)-Anatoxin A. The LD50 value of (±)-Anatoxin A was determined to be 1.25mg/kg, and at this particular dose (1.0×LD50) of toxin induced severe clinical symptom including extreme seizures in rats, resulting acute brain injuries in discrete brain regions, leading to 100% mortality within 5 min. The anticonvulsant effect, antiarrythmic effect, nerve conduction study, clinical observations and mortality, neuroprotective effect as well as skin histopathology of the prophylactic transdermal patch against (±)-Anatoxin A poisoning were investigated systematically. It was found that seizures, tachycardia, nerve damage, clinical symptoms, brain injuries and mortality induced by such lethal toxin were effectively prevented by the prophylactic patch treatment up to certain LD50 level. Hence, it could be a choice of potential therapeutic regimen against such lethal poisoning.

Topics: Animals; Anti-Arrhythmia Agents; Anticonvulsants; Arrhythmias, Cardiac; Brain; Cyanobacteria Toxins; Male; Neuroprotective Agents; Physostigmine; Pralidoxime Compounds; Rats, Wistar; Seizures; Skin; Transdermal Patch; Tropanes

The skin irritating, sensitizing, and acute dermal toxicity potential of a novel combinational prophylactic transdermal patch, mainly composed of eserine and pralidoxime chloride as active pharmaceutical ingredients, against (±) anatoxin-a poisoning were investigated in rabbits, guinea pigs, and rats in compliance with the Organisation for Economic Cooperation and Development guidelines. In primary skin irritation test, rabbits were dermally attached with the therapeutically active transdermal patch or with a placebo patch for 72 hours. The transdermal patches did not induce any adverse reactions such as erythema and edema on intact skin sites. The active patch was classified as a practically nonirritating material based on the score in the primary irritation index. In the Buehler test, guinea pigs were sensitized by the active or placebo transdermal patches attached for 24 hours. The patches did not induce any sensitization reactions in contrast to a severe sensitization reaction that occurred in the positive control. Therefore, the active patch and placebo patch were both graded as weak in sensitization score and rate. Acute dermal toxicity test in rats did not produce any overt signs of toxicity following a 14-day treatment period. Taken together, these findings suggest that the transdermal patch does not cause skin irritation, skin sensitization, or dermal toxic effects following dermal application.

Topics: Administration, Cutaneous; Animals; Cyanobacteria Toxins; Drug Evaluation, Preclinical; Female; Guidelines as Topic; Guinea Pigs; Male; Physostigmine; Pralidoxime Compounds; Rabbits; Rats; Skin; Skin Tests; Toxicity Tests, Acute; Transdermal Patch; Tropanes