Amitriptyline increases GABA-stimulated 36Cl- influx by recombinant (alpha 1 gamma 2) GABAA receptors.
WSS-1 cells expressing (alpha 1 gamma 2)GABAA receptors show an augmented 36Cl- response to GABA in the presence of amitriptyline that is increased by flumazenil, unlike augmentation by diazepam which is blocked by flumazenil. This amitriptyline effect is opposite to the inhibition of GABA-stimulated 36Cl influx manifested in membrane vesicles prepared from drug-naive rats or submissive rats (a model of depression) but is similar to that seen in tissue from amitriptyline-treated rats or dominant rats. The results suggest a novel mechanism of antidepressant drug action having a delayed onset.
Malatynska
E
E
Department of Pharmacology and Toxicology, Evansville Center, Indiana University School of Medicine 47712, USA. emalatyn@iupui.edu
Miller
C
C
Schindler
N
N
Cecil
A
A
Knapp
A
A
Crites
G
G
Rogers
H
H
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000235:genetics; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D018118:Chloride Channels; D018757:GABA Modulators; D011963:Receptors, GABA-A; D000639:Amitriptyline; D005680:gamma-Aminobutyric Acid; D003975:Diazepam