Amprolium

Quaternary Salts. Herbicides paraquat (20) and diquat (59) are the quaternary salts of 4,4 -bipyridine (19) and 2,2 -bipyridine with methyl chloride and 1,2-dibromoethane, respectively. Higher alkylpyridinium salts are used in the textile industry as dye ancillaries and spin bath additives. The higher alkylpyridinium salt, hexadecylpytidinium chloride [123-03-5] (67) (cetylpyridinium chloride) is a topical antiseptic. Amprolium (62), a quaternary salt of a-picohne (2), is a coccidiostat. Bisaryl salts of butylpyridinium bromide (or its lower 1-alkyl homologues) with aluminum chloride have been used as battery electrolytes (84), in aluminum electroplating baths (85), as Friedel-Crafts catalysts (86), and for the formylation of toluene by carbon monoxide (87) (see QuaternaryAA ONiUM compounds). 

The worldwide usage of polyether antibiotics for controlling coccidiosis is approximately 190 million compared to a total market of 210—220 million. Monensin and salinomycin represent about 65—70% of this market lasalocid, narasin, and maduramicin make up the remainder. Other compounds for coccidiosis control include nicarbazine, halofiinginone, amprolium, and robenidine. Worldwide usage is in excess of 3 million kg of product. 

Ampicillin—see Penicillin, D-n-aminobenzyl-Amprolium coccidiostat mode of action, 1, 212 as veterinary product, 2, 515 Amquinsin, 2, 517 Amylobarbitone metabolism, 1, 237 Anabasine, 2, 511 synthesis, 2, 385 Anabasine, N-methyl-N -oxide... 

Aminopyrine, 234 Aminotetradine, 265 2-Aminothiazole, 247 2-Aminothiazole synthesis, 126 Amisotetradine, 266 Amobarbital, 268 Amopyroquine, 342 Amoxycillin, 414 Amphetamine, 37, 70 Ampicillin, 413 Amprolium, 264 Amytriptylene, 141, 404 Anabolic effects, 169 Androgens, discovery, 155 Androstanolone, 173 Androstenedione, 158, 176 Anesthesia, parenteral, 56 Angst, 363 Anileridine, 300 Aniline, metabolism. 111 Anisindandione, 147 Anovlar , 186 Antagonists, 20, 65 Antazoline, 242 Antibodies, 41... 

A compound that includes an aminopyrimidine ring as well as the quaternary salt present in thiamine shows preferential inhibition of absorption of that co-factor by coccidia parasites over uptake by vertebrates. The compound is thus used in poultry where coccidiosis is an economically important disease. Condensation of ethoxymethylenemalononitrile (42-1) with the amidine (42-2) leads to the aminopyrimidine (42-4), probably via the intermediate addition-elimination intermediate (42-3). The nitrile group is then reduced to the methylamino derivative (42-5) by means of hthium aluminum hydride. Exhaustive methylation, for example by reaction with formaldehyde and formic acid, followed by methyl iodide leads to the quaternary methiodide (42-6). The quaternary salt is then displaced by bromine, and the resulting benzyhc-like cylic halide (42-7) is displaced by 2-picoline (42-8). There is thus obtained amprolium (42-9) [43]. 

Thus, tissue levels of amprolium and zoalene that can induce their own metabolism were higher in chickens at 3 weeks of dosing than at 8 weeks. This may explain, in part, why drugs such as these do not accumulate in body tissues... 

They are still widely used as feed additives for treatment or prevention of coccidiosis. In ruminants, sulfaquinoxaline, sulfadimethoxine, and sulfame-thoxypyridazine are the most useful coccidiostats, although sulfachlorpyrazine, sulfathiazole, and sulfamonomethoxine are also highly effective. Additional coccidiostats or adjuvants such as amprolium, chlortetracycline, and ethopabate are often combined with sulfonamides for synergistic effects in poultry. 

Amprolium (Fig. 5.7) is a vitamin IT analogue. It is a competitive antagonist of the thiamine transport mechanism. Amprolium has been used as a coccidi-ostat mainly in chickens, laying hens, turkeys, and ruminants. It is available as a soluble powder for addition to drinking water (60-240 mg/L) or as a premix, usually in combination with ethopabate and/or sulfaquinoxaline, for mixing with the feed (125-500 mg/kg feed). A withdrawal period of 3 days is required for chickens. 

Pharmacokinetic studies in chickens orally dosed with 12 or 20 mg amprolium/kg bw showed that maximum blood concentrations of 9.5 and 26 ppm, respectively, were achieved at 4 h after dosing. At 8 h after dosing, residue concentrations in kidney and cecum were 18 and 46 ppm, respectively, for the low-dose group, and 36 and 74 ppm, respectively, for the high-dose group. 

Residue depletion studies in chicks given a diet containing 150 or 250 mg amprolium/kg feed from day 1 to day 32 of age showed that amprolium concentrations at 0 day and 2 day withdrawal from the high-dose diet were 90 and less than 10 ppb, respectively, in muscle, 410 and less than 20 ppb, respectively, in liver, 380 and less than 40 ppb, respectively, in kidney, and 420 and less than... 

When hens were fed diets containing 5 or 250 mg amprolium/kg feed for... 

Ethopabate (Fig. 5.7) is a substituted benzoic acid having anticoccidial activity against a number of Eimeria species. It is always used in combination with amprolium. 

The higher potency of nicarbazin (57) compared with earlier agents then set a standard for new compounds. Moreover, parasite resistance to the existing agents was becoming problematic. In 1960 amprolium (58) was introduced. This compound had an entirely different mode of action. That the drug reduces the uptake of thiamine (59) by (or... 

The use of amprolium (58) at 125 p.p.m. in feed soon failed to give complete control of some Eimeria species. The closely related quinoline compounds, buquinolate (60) and decoquinolate (61), and the pyridine, clopidol (62), were introduced as replacement for amprolium (58). However, all the compounds have been beset by resistance problems and today the prophylactic treatment of coccidiosis is heavily dependent upon the sodium ionophore monensin (63). 

Pesticides. The compound 2-picoline is a component of l-[(4 -amino-2/- f-propyl-5 -pyrimidinyl )methyl]-2-picolinium chloride hydrochloride, known as Amprolium, a broad-spectrum coccidiostat. A newer coccidiostat is 3,5-dichloro-4-hvdToxy-2,6-lnfidine and known... 

Carbohydrate metabolism provides the main energy source in coccidia. Diets deficient in thiamin, riboflavin, or nicotinic acid—all cofactors in carbohydrate metabolism—result in suppression of parasitic infestation of chickens by E tenella and E acervulina. A thiamin analog, amprolium—1-[(4-amino-2-propyl-5-pyrimidinyl)-methyl]-2-picolinium chloride—has long been used as an effective anticoccidial agent in chickens and cattle with relatively low host toxicity. The antiparasitic activity of amprolium is reversible by thiamin and is recognized to involve inhibition of thiamin transport in the parasite. Unfortunately, amprolium has a rather narrow spectrum of antiparasitic activity it has poor activity against toxoplasmosis, a closely related parasitic infection. 

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