ANTAGONISM BY ANTIDEPRESSANTS OF NEUROTRANSMITTER RECEPTORS OF NORMAL HUMAN-BRAIN INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (1) , 94-102
Abstract
Using radioligand binding techniques, the equilibrium Kd were determined for a series of antidepressants at the histamine H1, muscarinic acetylcholine, .alpha.1- and .alpha.2-adrenergic and dopamine (D-2) receptors of normal human brain tissue obtained at autopsy. Different antidepressants (25) were studied at all but the D-2 receptor at which the number was 13 (including a metabolite of an antidepressant). Of all the receptor interactions studied, that at the histamine H1 receptor was in general the most potent interaction of this class of compounds, corresponding to results form studies using animal tissue as the source of receptors. At the human brain histamine H1 receptor, antidepressants remained among the most potent histamine H1 antagonists known, although their affinities for human receptors were lower than those for animal receptors. The most potent and the least potent compound at the receptors were doxepin (Kd = 0.24 nM) and fluvoxamine (Kd = 109 .mu.M) at the histamine H1 receptor; amitryptyline (Kd = 18 nM) and trazodone (Kd = 324 .mu.M) at the muscarinic receptor; doxepin (Kd = 24 nM) and viloxazine (Kd = 14 .mu.M) at the .alpha.1-receptor; mianserin (Kd = 73 nM) and bupropion (Kd = 81 .mu.M) at the .alpha.2-receptor; and amoxapine (Kd = 160 nM) and trazodone (Kd = 3800 nM) at the D-2 receptor, respectively. Compared to older drugs, the newer compounds tended to have lower affinities for these receptors.