New antimuscarinic agents for improved treatment of poisoning by cholinesterase inhibitors. Annual report, 1 November 1983-1 August 1984
The object of this project is to find a more effective antimuscarinic agent than atropine for use as an antidote for poisoning by organophosphate cholinesterase inhibitors. To start this search, 30 structurally diverse antimuscarinic agents have been selected for initial testing. These compounds are to be evaluated for peripheral and central antimuscarinic activity in a variety of in vitro and in vivo tests in addition to determining their effectiveness as antidotes (in combination with an oxime reactivator) for poisoning by soman. Twenty-two of the compounds have now been evaluated for their ability to block acetylcholine-induced contractions in guinea pig intestinal smooth muscle when compared to atropine. Ability to displace radiolabeled quinuclidinyl benzilate from muscarinic receptors of mouse brain homogenate has been determined for atropine, hyoscine and 26 of the compounds. Only triflupromazine appeared to have a distinctly greater affinity for brain receptors than muscle receptors to atropine. Intestinal smooth muscle blockade; oxotremorine tremor inhibition; muscarinic receptor subtypes.
- Research Organization:
- Virginia Commonwealth Univ., Richmond, VA (United States). Dept. of Medicinal Chemistry
- OSTI ID:
- 7227018
- Report Number(s):
- AD-B-131911/0/XAB; CNN: DAMD17-83-C-3026
- Country of Publication:
- United States
- Language:
- English
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