Molecular interaction of bupropion with nicotinic acetylcholine receptors

Research output: Contribution to journalReview article

Abstract

This minireview focuses on the anti-nicotinic properties of bupropion (BP) at the molecular and cellular levels. The main pharmacological mechanism is based on the fact that BP induces the release as well as inhibits the reuptake of neurotransmitters such as a dopamine (DA) and norepinephrine (NE). Additional mechanisms of action have been also determined. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the clinical 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. More specifically, BP inhibits presynaptic α4β2-containing AChRs in GABAergic neurons of the ventral tegmental area and α3β4-containing AChRs in the habenulo-intrerpeduncular pathway. This inhibition finally decreases the addictive effects mediated by nicotine. Based on studies on muscle AChRs at the molecular level, a sequential mechanism is hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and (3), BP interacts with a binding domain located between the serine (position 6') and valine (position 13') rings that is shared with other NCAs including, phencyclidine, tricyclic antidepressants, and serotonin selective reuptake inhibitors. This new evidence paves the way for further investigations using AChRs as targets for the action of safer antidepressants and novel anti-addictive compounds.

Original languageEnglish
Pages (from-to)185-197
Number of pages13
JournalJournal of Pediatric Biochemistry
Volume1
Issue number2
DOIs
StatePublished - 1 Jan 2010
Externally publishedYes

Fingerprint

Bupropion
Molecular interactions
Nicotinic Receptors
Cholinergic Receptors
Ion Channels
Dopamine
Norepinephrine
GABAergic Neurons
Phencyclidine
Ventral Tegmental Area
Tricyclic Antidepressive Agents
Serotonin Uptake Inhibitors
Valine
Nicotine
Serine
Antidepressive Agents
Neurons
Neurotransmitter Agents
Muscle
Pharmacology

Keywords

  • bupropion
  • Nicotine addiction
  • nicotinic acetylcholine receptors

Cite this

@article{e20cf1ccc2e8494aab4c6b92f4d3bffa,
title = "Molecular interaction of bupropion with nicotinic acetylcholine receptors",
abstract = "This minireview focuses on the anti-nicotinic properties of bupropion (BP) at the molecular and cellular levels. The main pharmacological mechanism is based on the fact that BP induces the release as well as inhibits the reuptake of neurotransmitters such as a dopamine (DA) and norepinephrine (NE). Additional mechanisms of action have been also determined. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the clinical 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. More specifically, BP inhibits presynaptic α4β2-containing AChRs in GABAergic neurons of the ventral tegmental area and α3β4-containing AChRs in the habenulo-intrerpeduncular pathway. This inhibition finally decreases the addictive effects mediated by nicotine. Based on studies on muscle AChRs at the molecular level, a sequential mechanism is hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and (3), BP interacts with a binding domain located between the serine (position 6') and valine (position 13') rings that is shared with other NCAs including, phencyclidine, tricyclic antidepressants, and serotonin selective reuptake inhibitors. This new evidence paves the way for further investigations using AChRs as targets for the action of safer antidepressants and novel anti-addictive compounds.",
keywords = "bupropion, Nicotine addiction, nicotinic acetylcholine receptors",
author = "Arias, {Hugo R.}",
year = "2010",
month = "1",
day = "1",
doi = "10.1055/s-0036-1586365",
language = "English",
volume = "1",
pages = "185--197",
journal = "Journal of Pediatric Biochemistry",
issn = "1879-5390",
number = "2",

}

Molecular interaction of bupropion with nicotinic acetylcholine receptors. / Arias, Hugo R.

In: Journal of Pediatric Biochemistry, Vol. 1, No. 2, 01.01.2010, p. 185-197.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Molecular interaction of bupropion with nicotinic acetylcholine receptors

AU - Arias, Hugo R.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - This minireview focuses on the anti-nicotinic properties of bupropion (BP) at the molecular and cellular levels. The main pharmacological mechanism is based on the fact that BP induces the release as well as inhibits the reuptake of neurotransmitters such as a dopamine (DA) and norepinephrine (NE). Additional mechanisms of action have been also determined. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the clinical 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. More specifically, BP inhibits presynaptic α4β2-containing AChRs in GABAergic neurons of the ventral tegmental area and α3β4-containing AChRs in the habenulo-intrerpeduncular pathway. This inhibition finally decreases the addictive effects mediated by nicotine. Based on studies on muscle AChRs at the molecular level, a sequential mechanism is hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and (3), BP interacts with a binding domain located between the serine (position 6') and valine (position 13') rings that is shared with other NCAs including, phencyclidine, tricyclic antidepressants, and serotonin selective reuptake inhibitors. This new evidence paves the way for further investigations using AChRs as targets for the action of safer antidepressants and novel anti-addictive compounds.

AB - This minireview focuses on the anti-nicotinic properties of bupropion (BP) at the molecular and cellular levels. The main pharmacological mechanism is based on the fact that BP induces the release as well as inhibits the reuptake of neurotransmitters such as a dopamine (DA) and norepinephrine (NE). Additional mechanisms of action have been also determined. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the clinical 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. More specifically, BP inhibits presynaptic α4β2-containing AChRs in GABAergic neurons of the ventral tegmental area and α3β4-containing AChRs in the habenulo-intrerpeduncular pathway. This inhibition finally decreases the addictive effects mediated by nicotine. Based on studies on muscle AChRs at the molecular level, a sequential mechanism is hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and (3), BP interacts with a binding domain located between the serine (position 6') and valine (position 13') rings that is shared with other NCAs including, phencyclidine, tricyclic antidepressants, and serotonin selective reuptake inhibitors. This new evidence paves the way for further investigations using AChRs as targets for the action of safer antidepressants and novel anti-addictive compounds.

KW - bupropion

KW - Nicotine addiction

KW - nicotinic acetylcholine receptors

UR - http://www.scopus.com/inward/record.url?scp=85021673422&partnerID=8YFLogxK

U2 - 10.1055/s-0036-1586365

DO - 10.1055/s-0036-1586365

M3 - Review article

AN - SCOPUS:85021673422

VL - 1

SP - 185

EP - 197

JO - Journal of Pediatric Biochemistry

JF - Journal of Pediatric Biochemistry

SN - 1879-5390

IS - 2

ER -