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Vincristine


ACCESSION NB: DB00541 (APRD00495)


TYPE: small molecule


GROUP: approved


DESCRIPTION:
Antitumor alkaloid isolated from Vinca Rosea. (Merck, 11th ed.)

VOLUME OF DISTRIBUTION: Not Available

CATEGORIES:
Antineoplastic Agents Antineoplastic Agents, Phytogenic Tubulin Modulators

ABSORPTION: Not Available

INDICATION:
For treatment of acute leukaemia, malignant lymphoma, Hodgkin's disease, acute erythraemia, acute panmyelosis

PHARMACODYNAMICS:
Vincristine is a vinca alkaloid antineoplastic agent used as a treatment for various cancers including breast cancer, Hodgkin's disease, Kaposi's sarcoma, and testicular cancer. The vinca alkaloids are structurally similar compounds comprised of 2 multiringed units, vindoline and catharanthine. The vinca alkaloids have become clinically useful since the discovery of their antitumour properties in 1959. Initially, extracts of the periwinkle plant (Catharanthus roseus) were investigated because of putative hypoglycemic properties, but were noted to cause marrow suppression in rats and antileukemic effects in vitro. Vincristine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death. Vincristine has some immunosuppressant effect. The vinca alkaloids are considered to be cell cycle phase-specific.

MECHANISM OF ACTION:
The antitumor activity of Vincristine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Like other vinca alkaloids, Vincristine may also interfere with: 1) amino acid, cyclic AMP, and glutathione metabolism, 2) calmodulin-dependent Ca2+-transport ATPase activity, 3) cellular respiration, and 4) nucleic acid and lipid biosynthesis.

PROTEIN BINDING:
~75%

METABOLISM:
Hepatic

TOXICITY:
IVN-RAT LD50 1300 mg/kg; IPR-MUS LD50 5.2 mg/kg

AFECTED ORGANISMS:
Humans and other mammals