Potentiation of chemotherapeutic effect of vincristine in vincristine resistant tumor bearing mice by calmodulin inhibitor clomipramine.

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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.

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