Streptozotocin

Streptozotocin (Streptozocin, STZ, Zanosar) is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine as an antineoplastic drug for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for Type 1 diabetes.

Psychologists have studied this and the cognitive side effects of the drug.

Usage
Streptozotocin is approved by the U.S. Food and Drug Administration (FDA) for treating metastatic cancer of the pancreatic islet cells. Since it carries a substantial risk of toxicity and rarely cures the cancer, its use is generally limited to patients whose cancer cannot be removed by surgery. In these patients, streptozotocin can reduce the tumor size and reduce symptoms (especially hypoglycemia due to excessive insulin secretion by insulinomas).

A typical dose is 500 mg/m2/day by intravenous injection, for 5 days, repeated every 4-6 weeks.

Streptozotocin is a glucosamine-nitrosourea compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2.

History
Streptozotocin was originally identified in the late 1950s as an antibiotic. The drug was discovered in a strain of the soil microbe Streptomyces achromogenes by scientists at the drug company Upjohn (now part of Pfizer) in Kalamazoo, Michigan. The soil sample in which the microbe turned up had been taken from Blue Rapids, Kansas, which can therefore be considered the birthplace of streptozotocin. Upjohn filed for patent protection for the drug in August 1958 and was granted in March 1962.

In the mid-1960s streptozotocin was found to be selectively toxic to the beta cells of the pancreatic islets, the cells that normally regulate blood glucose levels by producing the hormone insulin. This suggested the drug's use as an animal model of type I diabetes, and as a medical treatment for cancers of the beta cells. In the 1960s and 1970s the National Cancer Institute investigated streptozotocin's use in cancer chemotherapy. Upjohn filed for FDA approval of streptozotocin as a treatment for pancreatic islet cell cancer in November 1976, and approval was granted in July 1982. The drug was subsequently marketed as Zanosar. Streptozotocin is now marketed by the generic drug company Sicor (Teva).

References of interest to psychologists

 * Blokland, A., & Jolles, J. (1993). Spatial learning deficit and reduced hippocampal ChAT activity in rats after an icv injection of streptozotocin: Pharmacology, Biochemistry and Behavior Vol 44(2) Feb 1993, 491-494.
 * Fujii, E., & Nomoto, T. (1987). Central action of cesium chloride in streptozotocin-diabetic mice: Psychopharmacology Vol 93(2) Oct 1987, 173-177.
 * Hilakivi-Clarke, L. A., Wozniak, K. M., Durcan, M. J., & Linnoila, M. (1990). Behavior of streptozotocin-diabetic mice in tests of exploration, locomotion, anxiety, depression and aggression: Physiology & Behavior Vol 48(3) Sep 1990, 429-433.
 * Kamei, J., Ohhashi, Y., Aoki, T., & Kasuya, Y. (1991). Streptozotocin-induced diabetes in mice reduces the nociceptive threshold, as recognized after application of noxious mechanical stimuli but not of thermal stimuli: Pharmacology, Biochemistry and Behavior Vol 39(2) Jun 1991, 541-544.
 * Plaschke, K., & Hoyer, S. (1993). Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus: International Journal of Developmental Neuroscience Vol 11(4) Aug 1993, 477-483.
 * Ramanathan, M., Jaiswal, A. K., & Bhattacharya, S. K. (1998). Differential effects of diazepam on anxiety in streptozotocin induced diabetic and non-diabetic rats: Psychopharmacology Vol 135(4) Feb 1998, 361-367.
 * Sharma, M., & Gupta, Y. K. (2001). Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment: Life Sciences Vol 68(9) Jan 2001, 1021-1029.
 * Shimomura, Y., Shimizu, H., Takahashi, M., Sato, N., & et al. (1990). Ambulatory activity in streptozotocin-induced diabetic rats: Physiology & Behavior Vol 47(6) Jun 1990, 1153-1155.
 * Steger, R. W. (1990). Testosterone replacement fails to reverse the adverse effects of streptozotocin-induced diabetes on sexual behavior in the male rat: