title: Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine.
abstract: Clomipramine, which is used as antidepressant and possesses calmodulin inhibitory activity, circumvented partly the vincristine resistance in vivo. Although vincristine alone at 30-200 micrograms/kg did not confer a significant therapeutic effect in vincristine resistant P388 leukemia (P388/VCR)-bearing mice, clomipramine at doses of 20 to 50 mg/kg administered daily for 10 d with vincristine enhanced the chemotherapeutic effect of vincristine in P388/VCR-bearing mice. Approximately a 30% increase in life span occurred. Although the circumvention of vincristine resistance was not achieved perfectly, it could be speculated that more than 98-99% of vincristine resistant tumor cells which could not be killed by vincristine alone could be killed by this approach.
mesh_terms: D000818:Animals; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002997:Clomipramine / Q000627:therapeutic use*; D004351:Drug Resistance; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D051379:Mice; D014750:Vincristine / Q000627:therapeutic use*
chemical_list: D002147:Calmodulin; D014750:Vincristine; D002997:Clomipramine