The protective actions of some anticholinergic drugs in sarin poisoning

Abstract

Summary The central and peripheral anticholinergic activities of a series of drugs comprising atropine, hyoscine, caramiphen and one of its analogues, and three glycollic acid esters, have been measured. The ability of the same drugs used alone, and in conjunction with N‐methyl pyridinium‐2‐aldoxime methanesulphonate (P2S), to protect mice, rats and guinea‐pigs from the lethal effects of sarin has been assessed. No correlation was found to exist between central or peripheral anticholinergic activity and ability to protect from sarin. On the indirectly stimulated isolated rat phrenic nerve‐diaphragm preparation all drugs with the exception of hyoscine caused potentiation of responses to low frequency stimulation but partial block of responses to high frequency stimulation. The drugs did not reverse the effects of sarin on the phrenic nerve‐diaphragm preparation. It is concluded that a pharmacological action other than an anticholinergic one is involved, in part, in the protective actions against sarin of some of the drugs studied. Whether their effects on skeletal muscle are of any relevance in this respect is unresolved.

Cholinesterases, a Target of Pharmacology and Toxicology

“…for subcutaneous administrations to rat, the LD 50s are 193 μg/kg for tabun, 103 μg/kg for sarin, 75 μg/kg for soman, and 12 μg/kg for VX (ref. [84][85][86] ). Median lethal concentration and time (LCt 50 ) in rats for sarin is 150 mg/m 3 for ten minutes lasting inhalation 87 .…”

Sarin Poisoning in Guinea Pigs Compared to Reactivation of Acetylcholinesterase in Vitro as a Basis for Therapy

“…We fully agree with Ellin (1982) that guinea pigs respond differently from rats ("if subjected to combined pyridostigmine, atropine, and oxime therapy in organophosphate poisoning"). (Wills 1970) 0.07 (Sammet 1983) 0.4 (Lohs 1960) 0.42-0.59 (Wills 1970) 0.585 (Loomis 1956) 0.67 (Junod 1976) RATS 0.103 (Brimblecombe et al 1970) 0.045 (Ellin 1982) GUINEA PIGS 0.040 (Brimblecombe el al. 1970) 0.040 (Fonnum & Stern 1981) 0.060 (Lohs 1960) 0.060 (Wills 1970) 0.112 (own results) 0.034 Wills 1970 These aspects urgently support our call to put controls versus treated animals in a randomized sequence in all animal experiments with organophosphate poisoning.…”

“…As other authors (Lohs 1960;Wills 1970;Brimblecombe 1970;Fonnum & Sterri 1981) have reported lower doses to be effective, we injected our lowest dose (0.050 mg/kg) of sarin at two different times of the year. A first experiment with 6 guinea pigs on December 1982, was followed by a second experiment with the same number of animals on May, 1983.…”

Organophosphorus Chemical Warfare Agents

“…Before the advent of carbamate prophylaxis, pralidoxime methanesulfonate tablets were issued to the British military. DeCandole and McPhaill, 1957Anderson et al, 1991Gupta and Dettbarn, 1992Brimblecombe et al, 1970Lundy et al, 1978Wolfe et al, 1987Berry et al, 1971Gordon et al, 1978 …”