Vinblastine is an antimicrotubule drug

Medication

A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

 used to treat certain kinds of cancer

Cancer

Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

, including Hodgkin's lymphoma

Hodgkin's lymphoma

Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...

, non-small cell lung cancer

Lung cancer

Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...

, breast cancer

Breast cancer

Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...

, head and neck cancer, and testicular cancer

Testicular cancer

Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...

. It is also used to treat Langerhan cell histiocytosis.

History

Vinblastine was first isolated by Robert Noble

Robert Noble

Robert Laing Noble, was a Canadian physician who was involved in the discovery of vinblastine.Born in Toronto, Ontario, he received his M.D. from the University of Toronto in 1934 and a Ph.D...

 and Charles Thomas Beer

Charles Thomas Beer

Charles Thomas Beer, CM was a Canadian organic chemist who helped in the discovery of Vinblastine.Born in Leigh, Dorset, England, he received a D.Phil in Chemistry from Oxford in 1948. He came to North America in the early 1950s to the department of medical research at the University of Western...

 from the Madagascar periwinkle plant. Vinblastine's utility as a chemotherapeutic agent was first discovered when it was crushed into a tea. Consumption of the tea led to a decreased number of white blood cells

Leukopenia

Leukopenia is a decrease in the number of white blood cells found in the blood, which places individuals at increased risk of infection....

; therefore, it was hypothesized that vinblastine might be effective against cancers of the white blood cell

White blood cell

White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...

s such as lymphoma

Lymphoma

Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

.

Pharmacology

Vinblastine is a vinca alkaloid and a chemical analogue of vincristine

Vincristine

Vincristine , formally known as leurocristine, sometimes abbreviated "VCR", is a vinca alkaloid from the Catharanthus roseus , formerly Vinca rosea and hence its name. It is a mitotic inhibitor, and is used in cancer chemotherapy.-Mechanism:Tubulin is a structural protein that polymerizes to...

. It binds tubulin

Tubulin

Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...

, thereby inhibiting the assembly of microtubules. It is M phase cell cycle

Cell cycle

The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 specific since microtubules are a component of the mitotic spindle

Mitotic spindle

In cell biology, the spindle fibers are the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells...

 and the kinetochore

Kinetochore

The kinetochore is the protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart....

 which are necessary for the separation of chromosomes during anaphase

Anaphase

Anaphase, from the ancient Greek ἀνά and φάσις , is the stage of mitosis or meiosis when chromosomes move to opposite poles of the cell....

 of mitosis. Toxicities include bone marrow suppression

Bone marrow suppression

Bone marrow suppression or myelotoxicity or myelosuppression, is the decrease in cells responsible for providing immunity, carrying oxygen, and those responsible for normal blood clotting is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine...

 (which is dose-limiting), gastrointestinal

Gastrointestinal tract

The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

 toxicity, potent vesicant

Blister agent

A blister agent, or vesicant, is a chemical compound that causes severe skin, eye and mucosal pain and irritation. They are named for their ability to cause severe chemical burns, resulting in painful water blisters on the bodies of those affected...

 (blister-forming) activity, and extravasation

Extravasation

Extravasation is the accidental administration of intravenously infused medicinal drugs into the surrounding tissue, either by leakage , or direct exposure...

 injury (forms deep ulcers). Vinblastine paracrystals may be composed of tightly-packed unpolymerized tubulin or microtubules.

Vinblastine is reported to be an effective component of certain chemotherapy regimens, particularly when used with bleomycin, and methotrexate in VBM chemotherapy for Stage IA or IIA Hodgkin lymphomas. The inclusion of vinblastine allows for lower dosese of bleomycin and reduced overall toxicity with larger resting periods between chemotherapy cycles.

Mechanism of Action

Microtubule disruptive drugs like vinblastine, colcemid

Colcemid

Used in cytogenetics, colcemid, also known as demecolcine, is related to colchicine but it is less toxic. It depolymerises microtubules and limits microtubule formation , thus arresting cells in metaphase and allowing cell harvest and karyotyping to be performed.-Mechanism of Action:Colcemid is a...

, nocodazole

Nocodazole

Nocodazole is an anti-neoplastic agent which exerts its effect in cells by interfering with the polymerization of microtubules. Microtubules are one type of fibre which constitutes the cytoskeleton, and the dynamic microtubule network has several important roles in the cell, including vesicular...

 have been reported to act by two mechanisms. At very low concentrations they suppress microtubule dynamics and at higher concentrations they reduce microtubule polymer mass. Recent findings indicate that they also produce microtubule fragments by stimulating microtubule minus-end detachment from their organizing centers. Dose-response studies further indicate that enhanced microtubule detachment from spindle poles correlate best with cytotoxicity.

Isolation and Synthesis

Vinblastine may be isolated from the Madagascar Periwinkle (Catharanthus roseus), along with several of its precursors- catharanthine and vindoline. Extraction is costly and yields of vinblastine and its precursors are low. Enantioselective synthesis has been of considerable interest in recent years, as the natural mixture of isomers is not an economical source for the required C16’S, C14’R stereochemistry of biologically active vinblastine. Initially, the approach depends upon an enantioselective Sharpless epoxidation, which sets the stereochemistry at C20. The desired configuration around C16 and C14 can then be fixed during the ensuing steps. In this pathway, vinblastine is constructed by a series of cyclization and coupling reactions which create the required stereochemistry. The overall yield may be as great as 22%, which makes this synthetic approach more attractive than extraction from natural sources, whose overall yield is about 10 %.
Stereochemistry is controlled through a mixture of chiral agents (Sharpless catalysts), and reaction conditions (temperature, and selected enantiopure starting materials).

Indications

Vinblastine is a component of a number of chemotherapy regimens, including ABVD

ABVD

ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin lymphoma, supplanting the older MOPP protocol. It consists of concurrent treatment with the chemotherapy drugs:*Adriamycin *bleomycin...

 for Hodgkin lymphoma. It is also used to treat histiocytosis

Histiocytosis

In medicine, histiocytosis refers to an excessive number of histiocytes, , and is typically used to refer to a group of rare diseases which share this as a characteristic...

according to the established protocols of the Histiocytosis Association of America.