Ethotoin

One of the earliest preparations of this ring system starts with displacement of the hydroxyl of benzaldehyde cyanohydrin (125) by urea. Treatment of the product (126) with hydrochloric acid leads to addition of the remaining urea nitrogen to the nitrile. There is thus obtained, after hydrolysis of the imine (127), the hydantoin (128). Alkylation by means of ethyl iodide affords ethotoin (129)... 

Benzaldehyde cyanohydrin is reacted with urea to displace the hydroxyl group of the cyanohydrin. That intermediate is treated with HCI to convert the urea nitrogen to a nitrile. The resultant imine is hydrolyzed to the phenylhydantoin. Alkylation with ethyl iodide gives ethotoin, as described by A. Pinner in Chem. Ber. 21, 2325 (1888). 

Warfarin sodium Benzal acetophenone Alkofanone Benzaldehyde Butalamlne HCI Chloramphenicol Fenipentol Isocarboxazid Oxacillin sodium Penicillin G benzathine Phenylpropanolamine HCI Tripelennamine Benzaldehyde cyanohydrin Ethotoin... 

C2H5I 75-03-6) see Butibufen Cinoxacin Diethylstilbestrol Enoxacin Ethotoin Gallamine triethiodide Imiquimod Lomefloxacin Mosapride citrate Nalidixic acid Oxolinic acid Pefloxacin Pipemidic acid Tridihexethyl chloride Zaleplon... 

CNNa 143-33-9) see Alclofenac Alpidem Amphetaminil Atorvastatin calcium Azatadine Calcium pantothenate Carnitine Clopidogrel hydrogensulfate Clortermine Dexrazoxane Diclofenac Diloxanide Edetic acid Epinastine hydrochloride Ethosuximide Ethotoin Fenoprofen Ibuprofen Irbesartan Ketoprofen Lonazolac Mephenytoin Mepindolol Montelukast sodium Nabilone Oxymetazoline Paramethadione Pentorex Saquinavir Suprofen Thiamphenicol Tolmetin Trimazosin Zolpidem sodium cyanoborohydride... 

CH4N2O 57-13-6) see Alfuzosin Allantoin Amobarbital Barbital Bromisoval Butalbital Carbasalate calcium Carbromal Cyclopentobarbital Dimethadione Dipyridamole Enoximone Ethotoin Heptabarb Metaxalone Methyclothiazide Orotic acid Paramethadione Pentobarbital Phenacemide Phenetuiide Phenobarbital Phenytoin Proquazone Secbutabarbital Secobarbital Sulfadimethoxine Thalidomide Trimethadione... 

V-Subslilulion and 5,5-disubstitution prevent ring opening as demonstrated by various examples. Ethotoin (3-ethyl-5-phenylhydantoin, 4.230), in contrast to its /V-dcclhylalcd metabolite, was not detectably hydrolyzed by DHPase. No ring-opened metabolite was found for phenytoin (5,5-diphenyl-hydantoin, 4.231) or nirvanol (5-ethyl-5-phenylhydantoin, 4.232), which is the AT-demethylated metabolite of mephenytoin (4.233) [144],... 

Ethacrinic acid, 120 Ethambutol, 222 Ether cleavage, 314, 368 Ethionamide, 255 Ethisterone, 163, 172 Ethithiazide, 358 Ethoheptazine, 303 Ethopropazine, 373 Ethosuximide, 228 Ethotoin, 245 Ethoxysolamide, 327 Ethylestrenol, 170 Ethylmorphine, 287 Ethynodiol diacetate, 165, 186 Ethynodrel, 164 Ethynylestradiol, 162 Etonitazine, 325... 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Ethotoin Ethotoin, 3-ethyl-5-phenylimidazolidine-2,4-dione (9.1.5), is synthesized in basically the same manner as described above, which in this case involves the reaction of benzaldehyde oxynitrile (9.1.2), with urea or ammonium hydrocarbonate, which forms the intermediate urea derivative (9.1.3) which on acidic conditions (9.1.3) cycUzes to 5-phenylhydantoin (9.1.4). Alkylation of this product using ethyliodide leads to the formation of ethotoin (9.1.5) [3,4]. 

Ethotoin is less active and less toxic than phenytoin. It is used for the same indications as is phenytoin, i.e. for control of major and complex epileptic attacks. 

Ethotoin Tonic-clonic Psychomotor nd Liver renal excretion of metabolites... 

ETHOTOIN Administer in 4 to 6 divided doses/day. Take after food space doses as evenly as practical. 

Ethotoin has appeared to be of some value in the treatment of partial as well as generalized tonic-clonic seizures and to be relatively free of the typical adverse effects of phenytoin. Because of its low efficacy, it is rarely used and then only in combination with other agents. 

Ethotoin and mephenytoin are congeners of phenytoin that are marketed as AEDs in the United States. They are not widely used. 

Many congeners of phenytoin have been synthesized, but only three have been marketed in the USA, and one of these (phenacemide) has been withdrawn. The other two congeners, mephenytoin and ethotoin, like phenytoin, appear to be most effective against generalized tonic-clonic seizures and partial seizures. No well-controlled clinical trials have documented their effectiveness. The incidence of severe reactions such as dermatitis, agranulocytosis, or hepatitis is higher for mephenytoin than for phenytoin. 

Ethotoin may be recommended for patients who are hypersensitive to phenytoin, but larger doses are required. The adverse effects and toxicity are generally less severe than those associated with phenytoin, but the drug appears to be less effective. 

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