ACTION OF RESERPINE ON THE LETHAL EFFECT OF CYTOTOXIC ALKYLATING AGENTS

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Abstract
The protective effect of reserpine on the lethality of nitromin was found in mice, and the possible pharmacological mechanism of reserpine was investigated. Intraperitoneal administration of reserpine (1 mg/kg, 6 to 12 hr. before nitromin) or tetrabenazine (50 mg/kg, 2 to 4 hr. before nitromin) produced a marked reduction of the lethality of nitromin. Pretreatment with 200 mg/kg of iproniazid 24 hr. before reserpine abolished the protective action of reserpine. Administration of 5-HTP [5-hydroxy-tryptophane] after reserpine abolished the protective action of reserpine, but administration of DOPA [dihydroxyphenylalamine] had no effect on the protective action of reserpine. The lethality rate after nitromin corresponded to the levels of brain serotonin [5-hydroxytryp-amine] reduced by reserpine or tetrabenazine. Nitromin lethality was enhanced when serotonin was administered right before. Pretreatment of reserpine had no effect on the anticancer effect of nitromin. These facts suggest a relationship between inhibitory effect of reserpine on nitromin lethality and reduction in serotonin level in the brain.