Immunologic mimicry by a monoclonal antibody of the tricyclic anti-depressants' binding site on muscarinic acetylcholine receptors.

Inhibition constants of tricyclic anti-depressants and related drugs determined for a monoclonal anti-nortriptyline antibody were close to those previously calculated with the same compounds for the brain acetylcholine muscarinic receptor. A highly significant correlation was found between these two series of inhibition constants when no correlation existed between the inhibition constants for the antibody and those for other receptors. This suggests that the binding site for tricyclic anti-depressants on the antibody mimics the binding site for these ligands on muscarinic receptors. Although nortriptyline reveals a noncompetitive inhibition of N-methyl-scopolamine binding to muscarinic receptors, muscarinic ligands display weak or no binding to the antibody. These findings indicate that the binding site for tricyclic anti-depressants on the receptor is distinct from that for the muscarinic ligands.