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Paromomycin General Information Operating Range Paromomycin General Information Elemental formula: C23H45N5O14 Molecular weight: 615,23 g/mol Material class: Aminoglycoside CAS Registry Number: 7542-37-2 Operating range The active ingredient Paromomycin is a natural antibiotic that is extensively used in pharmaceutical industry. It acts as a prophylaxis and treatment agent of the hepatic encephalopathy, amoebic dysentery and is also used for präoperative reduction of ammonia forming intestine flora. According to the World Health Organization [1] it will also be applied to fight various parasitic diseases and is among to the most essential medicines at the present time. Studies from institute of OneWorld Health suggest that particularly in tropical areas ectoparasitically transmitted protozoan pathogens of leishmaniasis can be effectively medicated by this agent via intramuscular injection. This treatment, as a clinical study in India shows, is not less effective than the reference preparation Amphotericin B. Parallel to the recently completed approval process in India as well as the status of an orphan drug in the United States and Europe, there are additional clinical test phases for visceral leishmaniasis (black fever) in Africa [2]. The first time effectiveness from Paromomycin against cutaneous leishmaniasis were found in 1960s in the USSR [3]. History / Evolutionary origin Paromomycin was isolated first from Streptomyces krestomuceticus in the 1950s and introduced as Humatin by the pharmaceutical company Parke-Davis (now Pfizer) since the 1960s [4]. At hepatic encephalopathy this preparation is used. The disease causes brain damage as a result of liver dysfunction, by in the urea cycle insufficient metabolized ammonia. Paromomycin as Humatin capsules reduces the ammonia- producing bacteria in the intestine and thus ensures improved symptoms. Even today this antibiotic agent is still obtained from species of the genus Streptomyces. These are characterized by a specific secondary metabolism where substances are formed which are not essential for the survival of the organism and therefore unrestricted available for the extraction. This attribute is probably due to the antagonistic effect on soil fungi in their immediate habitat [5] and a evidence still existing binding properties of molecules that have been replaced by more complex processes in the course of evolution from the metabolism. These retained inhibitory interactions in certain process steps. The affinity of the antibiotic substances isolated from the different species can be recognized from the nitrogen-containing ringstructures. These make today about two- thirds of the clinically useful natural antibiotics [6]. However they are subject to a loss of antibiotic effectiveness with increasing age of their first use because of development of resistance, so in addition to older versions, such as Streptomycin, Paromomycin also suffered a decline as universal antibiotic treatment option [7]. Therefore, in contrast to the conventional treatments in the encephalopathy and amoebic dysentery, in which more effective drugs like Neomycin are present, today's medical importance of Paromomycin is reflected in new insights, such as leishmaniasis. Effects The effect of aminoglycoside antibiotics caused by binding to the 30S-Subunit of the bacterial ribosomes, while the 40S-Subunit of the human cells will be spared. The result is an impaired translation of mRNA, whereby defective proteins are formed. Built in the cell membrane they achieve the lysis of the cell. Fig. Paromomycin at the ribosomal RNA [8] The therapeutic index is fairly large and includes both gram-positive and gram-negative bacteria, and certain protozoan pathogens. However by the fact that paromomycin is hardly absorbed from the intestine, a systemic treatment only be possible via intramuscular injection. Side effects are loss of appetit, nausea, andstomach ache and diarrhoea. The latter can be a sign of a life-threatning infection of the intestine mucosa. In addition, it can be particularly at pre-damaged patients or in an incorrect dosage cause nephrotoxic effects and hearing impairment. _______________________________________________________________________ _ [1] World Health Organization's List of Essential Medicines. World Health Organization. Adults October 2013. [2] Davidson RN, den Boer M, Ritmeijer K . Paromomycin. Oxford Journal, Transactions of the Royal Society of Tropical Medicine & Hygiene. Volume 103, Issue 7, 653-660, 2009. [3] Neal RA, Murphy AG, Olliaro P, Croft SL. Aminosidine ointments for the treatment of experimental cutaneous leishmaniasis. Oxford Journal, Transactions of the Royal Society of Tropical Medicines & Hygiene. Volume 88, Issue 2, 223-225, 1994. [4] Humatin Kapsels. New Preparations and Appliances: Nuw Preparate en Toestelle. South African Journal of Laboratory and Clinical Medicine. 698, 13. August 1960. [5] http://www.spektrum.de/lexikon/biologie/streptomycetaceae/64244; 02.07.2014 [6] http://www.spektrum.de/lexikon/biologie/antibiotika/4027; 02.07.2014 [7] vgl. Dr. Schuh F. Enzyklopädie Naturwissenschaft und Technik. Band 1, A-D, 151. Verlag Moderne Industrie, München 1981. [8] http://www.organische-chemie.ch/chemie/2012/jun/nebenwirkungen.shtm; 13.07.2014.
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