Different interaction between tricyclic antidepressants and mecamylamine with the human α3β4 nicotinic acetylcholine receptor ion channel

@article{Arias2010DifferentIB,
  title={Different interaction between tricyclic antidepressants and mecamylamine with the human $\alpha$3$\beta$4 nicotinic acetylcholine receptor ion channel},
  author={Hugo Rub{\'e}n Arias and Katarzyna M Targowska-Duda and Dominik Feuerbach and Carl J. Sullivan and Ryszard Maciejewski and Krzysztof J{\'o}źwiak},
  journal={Neurochemistry International},
  year={2010},
  volume={56},
  pages={642-649}
}
The interaction of tricyclic antidepressants (TCAs) with the human (h)alpha3beta4 nicotinic acetylcholine receptor (AChR) in different conformational states was compared with that for mecamylamine by using functional and structural approaches including, Ca(2+) influx, radioligand binding, and molecular docking. The results established that: (a) [(3)H]imipramine binds to a single site with relatively high affinity (K(d) = 0.41 +/- 0.04 microM), (b) imipramine inhibits [(3)H]imipramine binding to… Expand
Tricyclic antidepressants and mecamylamine bind to different sites in the human alpha4beta2 nicotinic receptor ion channel.
TLDR
The data indicate that tricyclic antidepressants and mecamylamine efficiently inhibit the ion channel by interacting at different luminal sites, suggesting local conformational changes. Expand
Tricyclic antidepressants and mecamylamine bind to different sites in the human α 4 β 2 nicotinic receptor ion channel
The interaction of tricyclic antidepressants with the human (h) α4β2 nicotinic acetylcholine receptor in different conformational states was compared with that for the noncompetitive antagonistExpand
Interaction of ibogaine with human α3β4-nicotinic acetylcholine receptors in different conformational states
Abstract The interaction of ibogaine and phencyclidine (PCP) with human (h) α3β4-nicotinic acetylcholine receptors (AChRs) in different conformational states was determined by functional andExpand
Interaction of selective serotonin reuptake inhibitors with neuronal nicotinic acetylcholine receptors.
TLDR
SSRIs inhibit the most important neuronal AChRs with potencies and affinities that are clinically relevant by binding to a luminal site that is shared with tricyclic antidepressants. Expand
Catharanthine alkaloids are noncompetitive antagonists of muscle-type nicotinic acetylcholine receptors
TLDR
The data indicate that the catharanthine moiety is a minimum structural requirement for AChR inhibition including, ion channel blocking and desensitization, and that ibogaine and PCP bind to overlapping sites in the desensitized A ChR ion channel. Expand
Structure-activity relationship of ibogaine analogs interacting with nicotinic acetylcholine receptors in different conformational states.
TLDR
The results indicate that the size of the binding sites for ibogaine analogs, located between the serine and nonpolar rings and shared with TCP, is an important structural feature for binding and for inducing desensitization. Expand
Bupropion inhibits human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites
The interaction of (±)-bupropion [(±)-BP] with the human (h) α3β4 nicotinic acetylcholine receptor (AChR) is determined by functional and structural approaches. The Ca 2+ influx results indicate thatExpand
Molecular Interactions between Mecamylamine Enantiomers and the Transmembrane Domain of the Human α4β2 Nicotinic Receptor
TLDR
These findings provide, for the first time, a structural understanding of the allosteric modulation elicited by mecamylamine enantiomers at each hα4β2 stoichiometry and could be beneficial for the development of novel therapies for the treatment of several neurological disorders. Expand
(−)-Reboxetine inhibits muscle nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites
The interaction of (-)-reboxetine, a non-tricyclic norepinephrine selective reuptake inhibitor, with muscle-type nicotinic acetylcholine receptors (AChRs) in different conformational states wasExpand
Tricyclic antidepressants inhibit hippocampal α7* and α9α10 nicotinic acetylcholine receptors by different mechanisms.
TLDR
The molecular docking and functional results support the notion that imipramine noncompetitively inhibits α7 AChRs by interacting with two overlapping luminal sites, whereas it competitively inhibitsAlpha7, α9α10, and hippocampal α7* A ChRs at clinically relevant concentrations and by different mechanisms of action. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 39 REFERENCES
Molecular mechanisms of inhibition of nicotinic acetylcholine receptors by tricyclic antidepressants
TLDR
The results indicate that tricyclic antidepressants may increase the rate of long-lived desensitization from the open state as well as interact with resting, open, and desensitized channels. Expand
Inhibitory mechanisms and binding site location for serotonin selective reuptake inhibitors on nicotinic acetylcholine receptors.
TLDR
The high proportion of protonated fluoxetine and dizocilpine calculated at physiological pH suggests that the protonate drugs can be attracted to the channel mouth before binding deeper within the AChR ion channel between the leucine and valine rings, a domain shared with phencyclidine, finally blocking ion flux and inducing A ChR desensitization. Expand
Interaction of bupropion with muscle-type nicotinic acetylcholine receptors in different conformational states.
TLDR
The data indicate that bupropion first binds to the resting AChR, decreasing the probability of ion channel opening, and the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process. Expand
Noncompetitive antagonist binding sites in the torpedo nicotinic acetylcholine receptor ion channel. Structure-activity relationship studies using adamantane derivatives.
TLDR
There is a more obvious cutoff in the desensitized state than in the resting state, suggesting that the Desensitization process constrains the TCP locus, and a plausible location of neutral and charged adamantane derivatives is shown in a model of the resting ion channel. Expand
Tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting at different conformational states.
TLDR
The study reveals that tricyclic antidepressants inhibit homomeric Cys-loop receptors by acting through different mechanisms at open and closed conformational states and probably at two different domains, namely, the pore in the open state and the extracellular domain in the closed state. Expand
Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes.
TLDR
It is suggested that in chronic (i.e., therapeutic) application, S-(+)-mecamylamine might be preferable to R-(-)-micylamine in terms of equilibrium inactivation of neuronal receptors with decreased side effects associated with muscle-type receptors. Expand
Differentiation of the open and closed states of the ionic channels of nicotinic acetylcholine receptors by tricyclic antidepressants.
TLDR
These agents, particularly nortriptyline, point to several different binding sites of the ionic channel and are suitable tools for the separation of the effects on peak current amplitude from its time constant of decay. Expand
Identifying the binding site(s) for antidepressants on the Torpedo nicotinic acetylcholine receptor: [3H]2-azidoimipramine photolabeling and molecular dynamics studies.
TLDR
Docking and molecular dynamics results indicate that imipramine and PCP interact preferably with the M2 transmembrane segments in the middle of the ion channel, consistent with a model where PCP and TCA bind to overlapping sites within the lumen of the Torpedo nAChR ion channel. Expand
Is the inhibition of nicotinic acetylcholine receptors by bupropion involved in its clinical actions?
  • H. Arias
  • Chemistry, Medicine
  • The international journal of biochemistry & cell biology
  • 2009
TLDR
The dual antidepressant and anti-nicotinic activity of BP is currently considered to be mediated by its stimulatory action on the DA and NE systems as well as its inhibitory action on AChRs. Expand
Inhibition of neuronal nicotinic acetylcholine receptors by imipramine and desipramine.
TLDR
Results indicate that tricyclic antidepressants can inhibit neuronal nicotinic acetylcholine receptors by mechanisms which are distinct from their actions at non-neuronal nicotinia receptor agonist dimethylphenylpipersinium iodide. Expand
...
1
2
3
4
...