Effects of antidepressants on function and viability of human neutrophils.
BACKGROUND
Antidepressants are frequently used in chronic pain therapy and are under investigation as long-acting local anesthetics. Because of the structural similarities between antidepressants and local anesthetics, the authors hypothesized that these compounds act similarly, and they investigated the effects of nortriptyline, amitriptyline, imipramine, and fluoxetine on priming and activation of human polymorphonuclear neutrophils (hPMNs).


METHODS
Effects of 30-, 120-, and 240-min preincubation with nortriptyline (10(-7)-10(-4) M), amitriptyline (10(-6)-10(-3) M), imipramine (10(-6)-10(-3) M), or fluoxetine (10(-7)-10(-4) M) on O(2)- generation of platelet activating factor-primed (10-6 M) and/or formyl-methionyl-leucyl-phenylalanine-activated (10(-6) M) isolated hPMNs were determined. All data are reported as mean +/- SD (statistics: t test, P < 0.05).


RESULTS
Brief incubation in low concentrations of nortriptyline, amitriptyline, or fluoxetine (all at 10(-5) M) did inhibit priming but not activation of hPMNs. Imipramine (10(-5) M) affected neither priming nor activation. Prolonged incubation in lower concentrations of all antidepressants influenced neither priming nor activation. However, at higher concentrations, all four compounds exerted cytotoxic effects: virtually all hPMNs were killed by amitriptyline and imipramine (both at 10(-3) M) or nortriptyline and fluoxetine (both at 10(-4) M).


CONCLUSIONS
Antidepressants, in low concentrations, inhibited priming but not activation of hPMNs. However, at concentrations similar to those attained after local injection, and in marked contrast to local anesthetics, antidepressants are profoundly toxic to hPMNs.
Strümper
Danja
D
Department of Anesthesiology, Pain Therapy and Home Ventilation, University Hospital Maastricht, Netherlands.
Durieux
Marcel E
ME
Hollmann
Markus W
MW
Tröster
Barbara
B
den Bakker
Christel G
CG
Marcus
Marco A E
MA
D000928:Antidepressive Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D018687:Antidepressive Agents, Second-Generation / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D007202:Indicators and Reagents; D010972:Platelet Activating Factor; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine