Bisquaternary antidotes

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514305, 514318, 546133, 546137, 546193, 546194, A61K 3146, C07D40112

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active

046753265

ABSTRACT:
A novel series of antidotes against organophosphorus poisoning having both anti-muscarinic activity and reactivation potency, were synthesized and evaluated for their pharmacological efficacy.
The compounds are bisquarternary oxybismethylene(or:trimethylene)-bis-N-heterocycles.
The N-heterocycles are comprised of 2,3 or 4 mono-substituted pyridines, 3-substituted quinuclidines and 4-substituted N-methylpiperidines (exclusive of both groups in one molecule designating a substituted pyridine ring). Some of the compounds display a remarkably low acute toxicity in mice.
These antidotes have been shown to be effective against poisoning by a variety of organophosphorus compounds as well as carbamates. The compounds are also of value as active ingredients in ophthalmic preparations.

REFERENCES:
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F. Mobbiger in Handbuch der Experimentellen Pharmakologie, O. Eichler et al. (Editors), Springer Verlag, Berlin, 1963, pp. 921-968.
H. Kewitz et al., Arch. Biochem. Biophys. 64, 456 (1956).
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G. Amitai, et al., Biochem. Pharmacol., 29, 483 (1980).
J. Gordon, et al., Toxicol. App. Pharmacol., 43, 207 (1978).
J. Schenk, et al., Arch Toxicol., 36, 71 (1976).
M. D. Mashkovsky, First Intern. Pharmacol. Meeting, 7, 359 (1961).

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