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Antidepressants Noncompetitively Inhibit Nicotinic Acetylcholine Receptor Function
Author(s) -
Fryer John D,
Lukas Ronald J
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0721117.x
Subject(s) - nicotinic agonist , pharmacology , acetylcholine receptor , nicotinic acetylcholine receptor , neurotransmitter , acetylcholine , chemistry , agonist , epibatidine , neurotransmitter receptor , receptor , neuroscience , biology , biochemistry
: Nicotinic acetylcholine receptors (nAChRs) are diversemembers of the neurotransmitter‐gated ion channel superfamily and playcritical roles in chemical signaling throughout the nervous system. Thepresent study establishes for the first time the acute functional effects ofsertraline (Zoloft), paroxetine (Paxil), nefazodone (Serzone), and venlafaxine(Effexor) on two human and one chick nAChR subtype. This study also confirmsprevious findings of nAChR functional block by fluoxetine (Prozac). Functionof human muscle‐type nAChR (α1βγδ) in TE671/RD cells,human autonomic nAChR (α3β4α5 ±β2) in SH‐SY5Yneuroblastoma cells, or chick V274T mutant α7‐nAChR heterologouslyexpressed in native nAChR‐null SH‐EP1 epithelial cells was measured using 86 Rb + efflux assays. Functional blockade of human muscle‐type and autonomic nAChRs is produced by each of the drugs in the low to intermediate micromolar range, and functional blockade of chick V274T‐α7‐nAChR is produced in the intermediate to high micromolar range. Functional blockade is insurmountable by increasing agonist concentrations at each nAChR subtype tested for each of these drugs, suggesting noncompetitive inhibition of nAChR function. These studies open the possibilities that nAChR subtypes in the brain could be targets for therapeutic antidepressants and could play roles in clinical depression.