Pralatrexate, sold under the brand name Folotyn, is a medication used for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL).Pralatrexate was approved for medical use in  the United States in September 2009, as the first treatment for Peripheral T-cell Lymphoma (PTCL), an often aggressive type of non-Hodgkins lymphoma. Medical uses
Pralatrexate is indicated for the treatment of people with relapsed or refractory peripheral T-cell lymphoma (PTCL). Mechanism
Pralatrexate is a dihydrofolate reductase inhibitor. Discovery
Research on this class of drugs began in the 1950s at SRI International, where scientists were focused on developing new chemotherapies and antifolates that would be effective against tumor cells.In the late 1970s, researchers at Memorial Sloan Kettering Cancer Center discovered that cancerous cells take in natural folate through a protein identified as plasma membrane transporter (now referred to as "reduced folate carrier type 1" or "RFC-1"). Further research showed that when normal cells evolve into cancerous cells they often overproduce RFC-1 to ensure they get enough folate.A subsequent scientific collaboration was ultimately formed among SRI International, Memorial Sloan Kettering Cancer Center, and the Southern Research Institute with the intention of developing an antifolate with greater therapeutic selectivity – an agent that could be more effectively internalized into tumors (transported into the cells through RFC-1) and would be more toxic to cancer cells than normal cells.This collaboration, supported by the National Cancer Institute, led to the identification of pralatrexate in the mid-1990s. Pralatrexate was later licensed to Allos Therapeutics in 2002 for further development.
Cardiovascular symptoms include bradycardia, tachycardia, hypotension, hypertension, orthostatic tachycardia, exercise intolerance, and rhythm disorders. Death from the condition can occur, but is very rare.Dyspareunia and other ciguatera symptoms have developed in otherwise healthy males and females following sexual intercourse with partners suffering ciguatera poisoning, signifying that the toxin may be sexually transmitted. Diarrhea and facial rashes have been reported in breastfed infants of poisoned mothers, suggesting that ciguatera toxins migrate into breast milk.The symptoms can last from weeks to years, and in extreme cases as long as 20 years, often leading to long-term disability. Most people do recover slowly over time. Cause
Gambierdiscus toxicus is the primary dinoflagellate responsible for the production of a number of similar polyether toxins, including ciguatoxin, maitotoxin, gambieric acid and scaritoxin, as well as the long-chain alcohol palytoxin. Other dinoflagellates that may cause ciguatera include Prorocentrum spp., Ostreopsis spp., Coolia monotis, Thecadinium spp. and Amphidinium carterae. Diagnosis
Diagnosis is based on a persons symptoms together with having recently eaten fish. If a number of those who eat the same fish have symptoms the diagnosis becomes more likely. If some of the fish they had previously eaten is available this can also be tested to confirm the diagnosis. Other potential causes such as paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), scombrotoxin fish poisoning, and pufferfish poisoning should be excluded.The reversal of hot and cold sensations is an occasional symptom of CFP that may help differentiate it from intestinal "flu". Treatment
There is no known effective treatment or antidote for ciguatera poisoning.