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The Effects of AF-DX 116, a Cardioselective Muscarinic Antagonist, on the Negative Inotropic Action of Acetylcholine

The Effects of AF-DX 116, a Cardioselective Muscarinic Antagonist, on the Negative Inotropic Action of Acetylcholine

S I Baskin, R H Thomsen

Res Commun Chem Pathol Pharmacol. 1991 Jan;71(1):3-16.

PMID: 2024064

Abstract:

In superfused left atria from male guinea pigs, rats, and rabbits, myocardial contractility was measured before and after addition of acetylcholine (ACh) and AF-DX 116 ((11[[2-[(diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro- 6H-pyrido[2,3-b] [1,4]benzodiazepine-6-) one), a selective muscarinic antagonist. Characteristic dose-response curves for acetylcholine showing greater negative inotropic response with dose were seen. Increasing AF-DX 116 concentrations reversed the negative inotropy of acetylcholine and, in fact, increased the inotropic response approximately 100% and 50% above the baseline contractile force in a dose-dependent manner in the guinea pig and rabbit, respectively. This increase in contractility following AF-DX 116 addition was not observed in rat atria. The capacity of AF-DX 116 to produce the positive inotropic response only occurred at concentrations above 1 x 10(-5) M. The positive inotropic response of AF-DX 116 was antagonized by dl-propranolol, which suggests that the administration of AF-DX 116 at higher concentrations may unmask the effect of norepinephrine released from underlying viable adrenergic terminals which exist in the left atria.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP102394310	AF-DX 116		102394-31-0	Price

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