REVERSAL OF MULTIDRUG-RESISTANCE BY AMITRIPTYLINE IN-VITRO

Amitriptyline, a tricyclic antidepressant, was able to reverse the mul tidrug resistance efflux pump of human colon cancer subline SW 620 and multidrug resistant (mdr) mouse lymphoma cells by decreasing rhodamin e 123 efflux. The inhibitory effect of amitriptyline on the efflux pum p was dose dependent. An investigation was made of the effects of mous e tumour necrosis factor (TNF) alpha and interferon (IFN) gamma on the efflux pump activity of mdr 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 a mitriptyline and TNF-alpha.