Cholinolytics in the treatment of anticholinesterase poisoning. V. The effectiveness of Parpanit with oximes in the treatment of organophosphorus poisoning

Abstract

The effectiveness of Parpanit in the treatment of organophosphorus poisoning was examined and compared with that of atropine sulfate. The potency of Parpanit was assessed in the mouse, rat, hamster, guinea pig, and rabbit against sarin, tabun, soman, CMPF, and DSDP in treatments in which the oximes P2S and TMB4 were used both singly and together. The effectiveness of the treatments utilizing both cholinolytics varied with the species used for assay, with the oxime used in combination, and with the nature and level of challenge of the organophosphorus inhibitors. The mean activity of Parpanit relative to atropine taken from a total of 102 trials indicated it to be 4.2 times as effective, with the potency ratio varying from 0.17 to 100 depending on the specific test. The acute oral toxicity of Parpanit in weanling rats was 2.9 g/kg (2.4–3.4). In a chronic toxicity study where daily oral doses as high as 1/5 LD50 were applied for 30 days, no evidence of accumulative effects could be found nor was there any evidence that the protective capacity of Parpanit against sarin was affected by the extended application of the drug.

Evaluation of the toxicity, pathology, and treatment of cyclohexylmethylphosphonofluoridate (CMPF) poisoning in rhesus monkeys

“…Based on these findings CMPF is approximately 6-12 times less toxic than soman in the non-human primate. In other species, Coleman et al (1968) found that CMPF was approximately 2 fold less toxic than soman in rats. Our own studies in guinea pigs and mice indicate that CMPF is approximately 2-3 fold less toxic than soman (unpublished data).…”

“…The inhibitory potency of CMPF against AChE (rabbit brain) is similar to that of soman (Gray and Dawson 1987). The in vivo toxictiy of CMPF is similar to that of the chemical warfare agents tabun in mice and rats and to satin in rabbits (Coleman et al 1968). Human or bovine red blood cell AChE inhibited by CMPF undergoes dealkylation, a phenomenon known as "aging", in 4.6-37.7 hours (Hill and Thomas 1969).…”

“…AChE inhibited by CMPF is also reactivatible in vitro by oximes (Hill and Thomas 1969). Reports suggest that CMPF poisoning in rodents and rabbits is difficult to treat with atropine and currently available 0ximes such as pralidoxime chloride (2-PAM) and pralidoxime mesylate (P2S) (Coleman et al 1968;Binenfeld et al 1971). Furthermore, recent studies at the US Army Medical Research Institute of Chemical Defense suggest that pyridostigmine pretreatment in combination with atropine and 2-PAM post-exposure treatment does not significantly increase protection against lethality in CMPFintoxicated rodents (unpublished data).…”

Editorial [Hot Topic:Anti-Cancer-Drugs (Executive Editor: E. Bergmann-Leitner)]

“…The in vivo toxicity of cyclosarin is similar to that of tabun in mice and rats and to sarin in rabbits and it is approximately twofold lower than to soman in rats [69]. In guinea pigs the cyclosarin is two-threefold less toxic than soman [70].…”

Behavioral effects of non‐opioid antitussive anticonvulsants

“…Although we have recently presented evidence that muscarinic antagonism is not a likely mechanism for the potent anticonvulsant properties of caramiphen [Tortella et al, 1988b1, caramiphen may still have prominent behavioral effects and other central nervous system actions which are muscarinic in nature [Coleman et al, 1968;Herz et al, 19651. Physostigmine, in the present study, partially antagonized the effects of caramiphen on non-punished responding.…”