Inhibition of cyclic AMP formation in N1E-115 neuroblastoma cells is mediated by a non-cardiac M₂ muscarinic receptor subtype

The cardioselective muscarinic antagonist, AF-DX 116 ((11[2-[(diethyl-amino)-methyl]-O-1-piperidinyl]-5,11-dihydro-6H-pyrido-[2,3-b][1,4]-benzodiazepine-6-one), was weak at blocking the M₂ muscarinic receptor-mediated inhibition of cyclic adenosine monophosphate (cAMP) formation in mouse neuroblastoma cells (clone N1E-115). In contrast, the glandular-selective antagonists, hexahydro-sila-difenidol (HHSiD) and 4-diphenylacetoxy-N-methyl-pipedinine methiodide (4-DAMP), were quite potent at inhbiting this response, being 14- and 318-fold more potent than AF-DX 116 in this regard, respectively. According to the rank order of potency of these two classes of antagonists, these data provide the first pharmacological evidence that inhibition of cAMP formation in a neuronal tissue is mediated by a non-cardiac M₂ muscarinic receptor subtype.