PMID: 3754611May 5, 1986Paper

Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist

Life Sciences
A GiachettiE Montagna

Abstract

AF-DX 116 (see chemical name below) is a competitive antagonist of muscarine receptors in peripheral organs. In contrast to pirenzepine, its behaviour in functional experiments indicates selectivity for the M2 muscarinic subtype. In pithed rats AF-DX 116 inhibits vagally-induced bradycardia, an M2 response, (ED50 32 micrograms/kg i.v.) in preference to the M1-mediated pressor response to McN-A-343 (ED50 211 micrograms/kg i.v.). AF-DX 116 further discriminates among M2 receptors, showing a high affinity for the cardiac muscarine receptors. In isolated preparations, AF-DX 116 has a tenfold higher affinity for the muscarine receptors of the heart (pA2 7.33) than for those in smooth muscles (pA2 6.39-6.44). The same profile appears from animal studies, where the compound is a more potent antagonist of either endogenously or exogenously activated cardiac muscarine responses as compared to vascular, smooth muscle or secretory responses. In general, the ratios of potencies (ED50) observed in cardiac vs. other muscarine mediated functions ranged between 30 and 50. Atropine showed no discrimination, inhibiting all muscarine responses in the same range of doses. In the conscious dog intravenous AF-DX 116 increased basal heart rate, and c...Continue Reading

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Citations

Jul 1, 1990·Medicinal Research Reviews·C Melchiorre
Apr 1, 1989·Naunyn-Schmiedeberg's Archives of Pharmacology·U Lang, A Walland
Dec 1, 1990·Digestive Diseases and Sciences·A PfeifferM Herawi
Sep 1, 1995·Biulleten' eksperimental'noĭ biologii i meditsiny·Ia Iu BagrovN B Manusova
Dec 1, 1994·Archives of Pharmacal Research·S W LeeJ G Kim
Nov 6, 1989·Brain Research·J MurugaianH Sapru
Nov 10, 1987·European Journal of Pharmacology·F MartosR Hammer
Sep 13, 1988·European Journal of Pharmacology·L Noronha-BlobW J Kinnier
Oct 26, 1988·European Journal of Pharmacology·S B FreedmanE A Harley
Mar 15, 1988·European Journal of Pharmacology·E MonferiniH Ladinsky
Dec 6, 1988·European Journal of Pharmacology·M Eltze, V Figala
Nov 22, 1988·European Journal of Pharmacology·P T MännistöT Suolinna
Jul 14, 1988·European Journal of Pharmacology·J P DehayeJ Christophe
Jun 22, 1988·European Journal of Pharmacology·L Nilvebrant, B Sparf
Nov 28, 1989·European Journal of Pharmacology·P KostkaE E Daniel
Apr 25, 1989·European Journal of Pharmacology·N R Newberry, M J Gilbert
Aug 3, 1989·European Journal of Pharmacology·A D MichelR L Whiting
May 19, 1989·European Journal of Pharmacology·J C Mak, P J Barnes
Dec 4, 1990·European Journal of Pharmacology·S Chiba, M Tsukada
Jan 3, 1991·European Journal of Pharmacology·H DoodsN Mayer

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