Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine. 
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 Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine.

J Pharmacol Exp Ther 1999 Jan 1;288(1):88-92
Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine
Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine.
Fryer JD, Lukas RJ
Division of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona.
[Record supplied by publisher]
Nicotinic acetylcholine receptors (nAChR) are diverse members of the
neurotransmitter-gated ion channel
superfamily and play critical roles in chemical signaling throughout the
nervous system. The present study
establishes the acute functional effects of bupropion, phencyclidine, and
ibogaine on two human nAChR
subtypes. Function of muscle-type nAChR (alpha1betagammadelta) in TE671/RD
cells or of ganglionic
nAChR (alpha3beta4alpha5+/-beta2) in SH-SY5Y neuroblastoma cells was measured
with 86Rb+ efflux assay
s. Functional blockade of human muscle-type and ganglionic nAChR is produced by
each of the {*filter*} in the
low to intermediate micromolar range. Functional blockade is insurmountable by
increasing agonist
concentrations in TE671/RD and SH-SY5Y cells for each of these {*filter*},
suggesting noncompetitive
inhibition of nAChR function. Based on these findings, we hypothesize that
nAChR are targets of diverse
substances of abuse and agents used in anti{*filter*}ion/smoking cessation
strategies. We also hypothesize that
nAChR play heretofore underappreciated roles in depression and as targets for
clinically useful
antidepressants.


Sun, 10 Jun 2001 03:00:00 GMT
 
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