Niclosamide

Niclosamide [50-65-7] (2/5-dichloro-4 -nitrosahcylanihde) has been commonly used against tapeworms in small animals (5). Although tapeworms (cestodes) are frequently refractory to anthelmintics highly active against other intestinal parasites, they are sensitive to niclosamide as well as pra2iquantel [55268-74-1] and epsirantel. Pyrantel pamoate [22204-24-6] is probably the most common animal wormer used in the 1990s. 

Niclosamide. This dmg (6) is a halogenated sahcylanilide derivative, C23HgQ2N204. 

The modes of action for niclosamide are interference with respiration and blockade of glucose uptake. It uncouples oxidative phosphorylation in both mammalian and taenioid mitochondria (22,23), inhibiting the anaerobic incorporation of inorganic phosphate into adenosine triphosphate (ATP). Tapeworms are very sensitive to niclosamide because they depend on the anaerobic metaboHsm of carbohydrates as their major source of energy. Niclosamide has selective toxicity for the parasites as compared with the host because Httle niclosamide is absorbed from the gastrointestinal tract. Adverse effects are uncommon, except for occasional gastrointestinal upset. 

Niclosamide causes the tapeworm head to disengage from the intestinal wall of the host and the body wall of the parasite to disintegrate. The first... 

This dmg was used prior to the availabiUty of niclosamide and is considered less satisfactory for the treatment of tapeworms than niclosamide (24). It causes more side effects and produces severe nausea. Quinacrine, however, is preferred by some clinicians for the treatment of Taenia solium infection because, unlike niclosamide, it expels the worms intact, thus reducing the theoretical risk of cysticercosis (25). 

Drug 6-1574 has been demonstrated to ensure a 100% recovery of spontaneously Hymenolepis nana-infected albino mice given doses 2.5-5 times lower than the ED of phenasal (niclosamide) (94MI1). 

Nicarpi dine 2 150 Nicergoline 2, 478 Niclosamide , 94 Nicotinic acid 1, 253 Nicordanil 3, lT8 Nicotinyl aTcohol 253 Nidroxyzone 1, 228 Nifedipine 283 Nifenazone 1, 234 Nifluminic acid 1, 256 Nifuratrone 2, 2T8 Nifurdazil 2, 239 Nifurmide 239... 

Yamacillin Taiempiciiiin Yamafur Carmofur Yatrociclina Methacycline Yatrocin Nitrofurazone Yesdol Diphenidol YIestrol Ethinylestradiol Yobir Alprenolol HCI Yocio Clofibrate Yomesan Niclosamide Yonomol Inositol niacinate Yophadoi Diphenidol Yosimilon Trimetazidine Youfural Tegafur Ytrocin Erythromycin Yubekinon - Ubidecarenone Yurinex Bumetanide Yutopar Ritodrine Yxin Tetrahydrozoline HCI... 

Albendazole Bromoxanide Bunamidine Cambedazole Clioxanide Cyclobendazole Flubendazole Lobendazole Antihistaminics Mebendazole Niclosamide Nitramisole Nitrodan Oxantel Oxfendazole Oxibendazole Thenium Closylate... 

Synonyms Bay-2353 Bayer 2353, Niclosamida Anidra Niclosamidum Anhydri-cum Phenasal Bayluscide [1-4], Niclosamidum Niclosamid Niclosamida ... 

Niclosamide anhydrous Niclosmide, anhydre Niclosamid, Wassefereies. HL 2447, NSC 178296, WR 46234 [5]. 

Niclosamide was synthesized industrially by first chlorinating salicylic acid in chlorobenzene to yield 5-chlorosalicylic acid (I). Control of the amount of chlorine introduced is essential at this step, because an excess halogen leads to the formation of 3,5-dichlorosalicylic acid in addition to (I). When (I) is heated with 2-chloro-4-nitroaniline (II) in chlorobenzene (102— 104°C) in the presence of phosphorus oxychloride, niclosamide (III) is obtained [7]. 

Another alternate synthetic method for the manufacturing of niclosamide is reported [1], Phosphorus trichloride (PC13) is slowly introduced into a boiling xylene solution containing 5-chlorosalicylic acid and 2-chloro-4-nitroaniline in equimolar ratio and the heating continued for 3 h. Crystals of niclosamide separate on cooling and are recrystallized from ethanol [7,8], van Tonder et al. [9] prepared and characterized three crystal forms of niclosamide namely the anhydrate and the two monohydrates. 

Niclosamide is practically insoluble in water soluble 1 in 150 of ethanol, 1 in 400 of chloroform, and 1 in 350 of ether sparingly soluble in acetone [4]. 

Monkiedje et al. [10] investigated the fate of niclosamide in aquatic system both under laboratory and field conditions. The octanol/watcr partition coefficient (Kaw) of niclosamide was 5.880 x 10 4. Adsorption isotherm studies indicated that the Freundlich parameters (K, n) for niclosamide were 0.02 and 4.93, respectively, for powder activated carbon (PAC), and 9.85 x 10 5 and 2.81, respectively, for silt loam soil. The adsorption coefficient (Aoc) for the drug was 0.02 for PAC, and 4.34 x 10-3 for the same soil. Hydrolysis of niclosamide occurred in distilled water buffer at pH above 7. No photolysis of the drug was observed in water after exposure to long-wave UV light for 4 h. Similarly, neither chemically volatilized from water following 5 h of sample aeration. Under field conditions, niclosamide persisted in ponds for over 14 days. The half-life of niclosamide was 3.40 days. 

The X-ray powder diffraction pattern of niclosamide has been measured using a Philips PW-1050 diffractometer, equipped with a single-channel analyzer and using a copper Ka radiation. The pattern obtained is shown in Fig. 1, and the data of scattering angle (degrees 20) and the relative intensities (///max) are found in Table 1. 

Table 1. Scattering angles and relative intensities in the X-ray powder diffraction pattern of niclosamide...

The liquid composition of niclosamide and a nonaqueous liquid carrier in an encapsulating agent was investigated [13]. 

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