Inhibitory effects of amantadine on the production of pro-inflammatory cytokines by stimulated in vitro human blood.
Treatment with amantadine (AMA), an N-methyl-D-aspartate (NMDA) receptor antagonist and antidepressant drug, increased the antidepressant activity of subsequent drugs in experimental studies and in patients suffering from treatment-resistant depression (TRD). Recent evidence indicates that depression may be accompanied by activation of an inflammatory response. These data indicate that pro-inflammatory cytokines may play a role in the etiology of depression, particularly in TRD. The present in vitro study shows the ability of AMA, used at concentrations between 10(-7) to 10(-5) M, to reduce the production of the pro-inflammatory cytokines, specifically interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In addition, AMA treatment increased the production of the negative immunoregulator, interleukin-10 (IL-10). Furthermore, the combined treatment of AMA with fluoxetine (FLU), but not imipramine (IMI), had a stronger immunomodulatory effect on cytokine production than AMA alone. The above data provide additional rationale for the treatment of patients suffering from depression with a combination of AMA and a selective serotonin reuptake inhibitor.
Kubera
Marta
M
Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. kubera@if-pan.krakow.pl
Maes
Michael
M
Budziszewska
Bogusława
B
Basta-Kaim
Agnieszka
A
Leśkiewicz
Monika
M
Grygier
Beata
B
Rogóz
Zofia
Z
Lasoń
Władysław
W
D000328:Adult; D000547:Amantadine / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D016753:Interleukin-10; D007371:Interferon-gamma; D000547:Amantadine; D007099:Imipramine