Smith C B, Garcia-Sevilla J A, Hollingsworth P J
Brain Res. 1981 Apr 6;210(1-2):413-8. doi: 10.1016/0006-8993(81)90919-7.
After two weeks of twice-daily administration of amitriptyline to rats, the binding of [3H]clonidine to presynaptic alpha 2-adrenoreceptors was decreased in membranes isolated from 5 areas of the rat brain. After one day of treatment, binding did not differ from saline treated controls. In vitro, a high concentration of amitriptyline caused a competitive inhibition of [3H]clonidine binding but did not alter the number of binding sites. The decrease in the number of alpha 2-adrenoreceptor binding sites after two weeks of amitriptyline treatment would explain the subsensitivity of these receptors which occurs after prolonged administration of antidepressant drugs.
