Diamidines, aromatic

Pentamidine is an aromatic diamidine. Pentamidine uptake by the parasite is mediated by several different adenosine transporters. The mode of action is unclear. 

Pharmacology Pentamidine isethionate, an aromatic diamidine antiprotozoal agent, has activity against P. carinii. In vitro studies indicate that the drug interferes with nuclear metabolism and inhibits the synthesis of DNA, RNA, phospholipids, and protein synthesis. 

Pentamidine is an aromatic diamidine formulated as an isoethionate salt used parenterally (4 mg/kg IM or slow IV injection). It has activity against trypanosomatid protozoans and against Pneumocystis carinii. It probably interacts with kineto-plast DNA and inhibits topoisomerase II. 

Pentamidine is an aromatic diamidine (Figure 52-3) formulated as an isethionate salt. Pentamidine is only administered parenterally. The drug leaves the circulation rapidly, with an initial half-life of about 6 hours, but it is bound avidly by tissues. Pentamidine thus accumulates and is eliminated very slowly, with a terminal elimination half-life of about 12 days. The drug can be detected in urine 6 or more weeks after treatment. Only trace amounts of pentamidine appear in the central nervous system, so it is not effective against central nervous system African trypanosomiasis. Pentamidine can also be inhaled as a nebulized powder for the prevention of pneumocystosis. Absorption into the systemic circulation after inhalation appears to be minimal. The mechanism of action of pentamidine is unknown. 

These aromatic diamidines inhibit IL-1 production and also block IL-6 and TNF. Imidazoline blocks IL-1 and TNF and is less toxic to the cell with an in vitro LD50 1(H. Examples of these compounds are... 

Diniiiiazeiie, an aromatic diamidine (Fig. 5.7), is a veterinary drug employed for die treatment of piroplasmosis and trypanosomiasis. A combination product consisting of 44.5% diminazene and 55.5% phenazone is authorized for use in cattle, sheep, and horses at an intramuscular dosage of 3.5 mg/kg bw. Diminazene acts against Babesia by affecting the fine structure and function of... 

Schoenbach EBGE.The pharmacology, mode of action, and therapeutic potentialities of stilbamidine, pentamidine, propamidine and other aromatic diamidines. A review. Medicine. 1948 27 327-77. 

Wien R FW, Scotcher NM.The metabolic effects produced by certain aromatic diamidines. Ann Trop Med Parasitol. 1943 37 19-33. 

Makulu DR, Waalkes TP. Interaction between aromatic diamidines and nucleic acids possible implications for chemotherapy. Journal of the National Cancer Institute. 1975 Feb 54(2) 305-9. 

Capillary Electrophoresis and HPLC for Analysis of Aromatic Diamidines,... 

The aim of the work reported here was to study how changes in the principal parameters for each technique affect the separation processes when analyzing a series of aromatic diamidines, and, based on the results obtained, to establish comparisons between the two analytical techniques. 

The aromatic diamidines are compounds of considerable pharmaceutical interest. This is, among others, for the following reasons they have a strong antiprotozoan action and participate in the metabohsm and transport of polyamines, inhibiting, for instance, S -adenosyl-L-methi-onine decarboxylase (SAMDC). Therefore, because this route is closely linked to cell proliferation processes, aromatic diamidines can slow down or prevent the growth of tumors.The substances used in this work are as follows ... 

Table 2 Performance of HPLC and CE in separation of aromatic diamidines...

CE for nine aromatic diamidines. The results obtained are noted and discussed in the tables, comparative features of the two techniques that emerge from the data collected are recorded. 

Rabanal, B. Negro, A. Study of nine aromatic diamidines designed to optimize their analysis by HPLC. J. Liq. Chromatogr. 2003, 26 (20), 3499-3512. 

The complex urea compoimds are related to the aromatic diamidines. Their mechanism of action is unknown. 

Pentamidine is an aromatic diamidine that was initially synthesized in the 1930s in a search for hypoglycemic agents. Because of its antiprotozoal activity, pentamidine has been used extensively for treatment and chemoprophylaxis of African trypanosomiasis. The exact mechanism of action of pentamidine is not known in vitro, it has been found to interfere with folate metabolism, anaerobic glycolysis, oxidative phosphorylation, and nucleic acid replication [1], Pentamidine usually is given parenterally in a dose of 4mg/kg/day as the isethionate salt, the only preparation available in the United States [1], Administration must be parenteral because gastrointestinal absorption is poor. Adverse reactions to pentamidine appear to be dose dependent, in that a 3-g total dose, which usually is reached in the second week of parenteral therapy, frequently causes toxicity [2]. 

Several new compounds have been reported that affect the formation of a fibrin clot. Aromatic diamidines, such as, 21, were reported to inhibit several proteolytic enzymes including thrombin.74 Concanavalin A (a globulin protein from the jack bean) inhibits fibrin formation by inhibiting the lipoprotein cofactor in the production of thrombin and thus decreasing the rate of thrombin production.75 Several antibiotics (penicillins and cephalosporins) have been reported to affect fibrin clot formation as well as platelet function. Cephalothin (22) has been shown to delay fibrin polymerization and thus prolong the activated partial thromboplastin time (APTT) and thrombin time tests.78... 

Propamidine and dibromopropamidine isetionates are aromatic diamidine antiseptics. They have been used for the treatment of bacterial conjunctivitis for more than 60 years and have always been available without prescription, but chloramphenicol is considered the drug of choice and the British National Formulary regards propamidine and dibromopropamidine as of little value. 

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