Reversal of multidrug resistance by amitriptyline in vitro.
Amitriptyline, a tricyclic antidepressant, was able to reverse the multidrug resistance efflux pump of human colon cancer subline SW 620 and multidrug resistant (mdr) mouse lymphoma cells by decreasing rhodamine 123 efflux. The inhibitory effect of amitriptyline on the efflux pump was dose dependent. An investigation was made of the effects of mouse tumour necrosis factor (TNF) alpha and interferon (IFN) gamma on the efflux pump activity of mdr cells together with amitriptyline compared to the par cells (mdr-). After long-term cytokine pretreatment of mdr cells, the amitriptyline was more effective, due to some synergism between the amitriptyline and TNF-alpha.
Varga
A
A
Department of Parasitology, Humboldt-University, Berlin, Germany.
Nugel
H
H
Baehr
R
R
Marx
U
U
Hevér
A
A
Nacsa
J
J
Ocsovszky
I
I
Molnar
J
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001693:Biological Transport, Active / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000493:pharmacokinetics; D008223:Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D051379:Mice; D011994:Recombinant Proteins; D020112:Rhodamine 123; D012235:Rhodamines / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000929:Antidepressive Agents, Tricyclic; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D012235:Rhodamines; D014409:Tumor Necrosis Factor-alpha; D000639:Amitriptyline; D020112:Rhodamine 123; D007371:Interferon-gamma