Fluoxetine Increases GABA(A) Receptor
Activity through a Novel Modulatory Site
by
Robinson RT, Drafts BC, Fisher JL.
Department of Pharmacology,
Physiology and Neuroscience,
University of South Carolina School of Medicine,
Columbia, South Carolina.
J Pharmacol Exp Ther 2003 Mar;304(3):978-84

ABSTRACT

Fluoxetine is a selective serotonin reuptake inhibitor used widely in the treatment of depression. In contrast to the proconvulsant effect of many antidepressants, fluoxetine has anticonvulsant activity. This property may be due in part to positive modulation of the GABA(A) receptors (GABARs), which mediate most fast inhibitory neurotransmission in the mammalian brain. We examined the effect of fluoxetine on the activity of recombinant GABARs transiently expressed in mammalian cells. Fluoxetine increased the response of the receptor to submaximal GABA concentrations but did not alter the maximum current amplitude. Sensitivity did not depend upon the beta- or gamma-subtype composition of the receptor when coexpressed with the alpha(1) subunit. Among the six alpha subtypes, only the alpha(5) subunit conferred reduced sensitivity to fluoxetine. The metabolite norfluoxetine was even more potent than fluoxetine. Mutations at residues in the alpha(5) subunit that alter its sensitivity to zinc or selective benzodiazepine derivatives did not affect potentiation by fluoxetine. This suggests that fluoxetine acts through a novel modulatory site on the GABAR. The direct positive modulation of GABARs by fluoxetine may be a factor in its anticonvulsant activity.

GABA
SSRIs
SSRIs 2006
Prozac on tap?
Fluoxetine.info
Fluoxetine and LSD
Fluoxetine and PMT
Fluoxetine and weight
Fluoxetine and bipolars
Fluoxetine and oxytocin
Fluoxetine and GABA(A)
Fluoxetine : side-effects
Post-E Prozac protection?
Antidepressant mechanisms
Comparisons and metabolites
Fluoxetine (Prozac) : structure
Fluoxetine (Prozac) and 5-HT2c
Fluoxetine and the opioid pathways

Refs
and further reading

HOME
HedWeb
Nootropics
cocaine.wiki
Future Opioids
BLTC Research
MDMA/Ecstasy
Superhapiness?
Utopian Surgery?
The Abolitionist Project
The Hedonistic Imperative
The Reproductive Revolution
Critique of Huxley's Brave New World

The Good Drug Guide
The Responsible Parent's Guide
To Healthy Mood Boosters For All The Family