Abstract
1. 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.
2. 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.
3. No correlation was found to exist between central or peripheral anticholinergic activity and ability to protect from sarin.
4. 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.
6. 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.
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Selected References
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- BROWN R. V. The effects of intracisternal sarin and pyridine-2-aldoxime methyl methanesulphonate in anesthetized dogs. Br J Pharmacol Chemother. 1960 Mar;15:170–174. doi: 10.1111/j.1476-5381.1960.tb01227.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bebbington A., Brimblecombe R. W. Muscarinic receptors in the peripheral and central nervous systems. Adv Drug Res. 1965;2:143–172. [PubMed] [Google Scholar]
- Brimblecombe R. W., Everett S. D. Actions of a cholinergic antagonist on mammalian skeletal muscle. Br J Pharmacol. 1969 May;36(1):172P–173P. [PMC free article] [PubMed] [Google Scholar]
- Brimblecombe R. W., Green D. M. The peripheral and central actions of some anticholinergic substances. Int J Neuropharmacol. 1968 Jan;7(1):15–21. doi: 10.1016/0028-3908(68)90050-6. [DOI] [PubMed] [Google Scholar]
- COLEMAN I. W., LITTLE P. E., BANNARD R. A. CHOLINOLYTICS IN THE TREATMENT OF ANTICHOLINESTERASE POISONING. III. THE EFFECTS OF QUATERNIZATION AND ALTERATION OF ANIONIC FUNCTION OF THE POTENCY OF CHOLINOLYTICS IN THE TREATMENT OF SARIN POISONING. Can J Biochem Physiol. 1963 Dec;41:2479–2491. [PubMed] [Google Scholar]
- COLEMAN I. W., LITTLE P. E., BANNARD R. A. Cholinolytics in the treatment of anticholinesterase poisoning. I. The effectiveness of certain cholinolytics in combination with an oxime for treatment of sarin poisoning. Can J Biochem Physiol. 1962 Jun;40:815–826. [PubMed] [Google Scholar]
- Cox B., Potkonjak D. The effects of atropine and dyflos on tremor and increase in whole brain acetylcholine produced by injection of oxotremorine in the rat. Br J Pharmacol. 1969 Mar;35(3):521–529. doi: 10.1111/j.1476-5381.1969.tb08293.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cox B., Potkonjak D. The relationship between tremor and change in brain acetylcholine concentration produced by injection of tremorine or oxotremorine in the rat. Br J Pharmacol. 1969 Feb;35(2):295–303. [PMC free article] [PubMed] [Google Scholar]
- DAVIES D. R., GREEN A. L., WILLEY G. L. 2-Hydroxyiminomethyl-N-methylpyridinium methanesulphonate and atropine in the treatment of severe organophosphate poisoning. Br J Pharmacol Chemother. 1959 Mar;14(1):5–8. doi: 10.1111/j.1476-5381.1959.tb00920.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DOUGLAS W. W., MATHEWS P. B. C. Acute tetraethylpyrophosphate poisoning in cats and its modification by atropine or hyoscine. J Physiol. 1952 Feb;116(2):202–218. doi: 10.1113/jphysiol.1952.sp004700. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FIREMARK H., BARLOW C. F., ROTH L. J. THE PENETRATION OF 2-PAM-C14 INTO BRAIN AND THE EFFECT OF CHOLINESTERASE INHIBITORS ON ITS TRANSPORT. J Pharmacol Exp Ther. 1964 Aug;145:252–265. [PubMed] [Google Scholar]