Weak binding of 10-hydroxymetabolites of nortriptyline to rat brain muscarinic acetylcholine receptors.
The relative affinities of nortriptyline (NT) and its 10-hydroxymetabolites to rat brain muscarinic acetylcholine receptors have been determined by competition with 3H-quinuclidinyl benzilate binding. It is shown that the major NT metabolite, E-10-OH-NT, has only 1/18 the affinity of NT for the muscarinic receptor. Since this metabolite is equipotent to NT in inhibiting neuronal noradrenaline uptake, it is suggested that it might be of clinical value as an antidepressant by virtue of having less anticholinergic side-effects than NT itself.
D000639:Amitriptyline / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009661:Nortriptyline / Q000031:analogs & derivatives* / Q000378:metabolism*; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000378:metabolism*; D013237:Stereoisomerism
D011976:Receptors, Muscarinic; C013567:10-hydroxynortriptyline; D000639:Amitriptyline; D011813:Quinuclidinyl Benzilate; D009661:Nortriptyline