Amitriptyline: long-term treatment elevates alpha-adrenergic and muscarinic receptor binding in mouse brain.
The effects of long-term treatment of the tricyclic antidepressant drug, amitriptyline, on alpha-adrenergic, muscarinic and dopaminergic receptor binding were studied in mouse brain. No changes could be observed after 7 or 14 days of amitriptyline administration, but after 21 days a two-fold increase in alpha-adrenergic binding was detected in the medulla pons and in the hippocampus using [3H]WB-4101 as the binding ligand. In the same two regions, a moderate increase in muscarinic receptor binding (25%) as measured by [3H]4NMPB was seen, while no change was detected in dopaminergic receptor binding measured by [3H]spiperone. Scatchard analysis reveals that the increases in receptor densities are not a result of changes in the dissociation constants of the tritiated drugs for their receptors. It is suggested that the increase in alpha-adrenergic as well as in muscarinic binding is a consequence of a chronic blockade of these two types of receptors by amitriptyline in vivo.
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001561:Benzilates / Q000378:metabolism; D001921:Brain / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D011149:Pons / Q000187:drug effects; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D001561:Benzilates; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D000639:Amitriptyline; D013134:Spiperone