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

  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},

Tricyclic antidepressants and mecamylamine bind to different sites in the human α 4 β 2 nicotinic receptor ion channel

The data indicate that tricyclic antidepressants and mecamylamine efficiently inhibit the ion channel by interacting at different luminal sites, suggesting local conformational changes in the desensitized state.

Interaction of ibogaine with human α3β4-nicotinic acetylcholine receptors in different conformational states

Interaction of selective serotonin reuptake inhibitors with neuronal nicotinic acetylcholine receptors.

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.

Bupropion inhibits human α3β4 nicotinic acetylcholine receptors by interacting with luminal and non-luminal sites

The results are consistent with a hα3β4 model where BP and SADU-3-72 bind to overlapping non-luminal sites as well as non-overlapping luminal sites, probably in physiological conditions.

Molecular Interactions between Mecamylamine Enantiomers and the Transmembrane Domain of the Human α4β2 Nicotinic Receptor

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.



Interaction of bupropion with muscle-type nicotinic acetylcholine receptors in different conformational states.

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.

Noncompetitive antagonist binding sites in the torpedo nicotinic acetylcholine receptor ion channel. Structure-activity relationship studies using adamantane derivatives.

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.

Analysis of mecamylamine stereoisomers on human nicotinic receptor subtypes.

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.

Differentiation of the open and closed states of the ionic channels of nicotinic acetylcholine receptors by tricyclic antidepressants.

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.

Is the inhibition of nicotinic acetylcholine receptors by bupropion involved in its clinical actions?

  • H. Arias
  • Biology
    The international journal of biochemistry & cell biology
  • 2009