Anticonvulsant hydantoins

Significant drug-drug interactions are those that potentiate the effects of other agents and require dosage modification. These include certain anticoagulants, hypoglycemic sulfonylureas, and hydantoin anticonvulsants. 

It is a hydantoin anticonvulsant with actions and uses resembling to those of phenytoin but it is foimd to be relatively more toxic. On account of its high degree of toxicity it is exclusively given to such patients who do not response to other treatments. 

Ethoxycarbonyl-3,5-diphenyl-hydantoin, anticonvulsant Rat loss of ethoxycarbonyl... 

Many hydantoins are endowed with significant pharmacological activities as highlighted by 5,5-diphenylhydantoin (Dilantin ), an anticonvulsant and antiepileptic discovered by Parke-Davis in 1940 s. Despite the lapse of more than half a century, Dilantin still plays an important rote in modem medicine. Meanwhile, another anticonvulsant 15 was synthesized from 9,10-dimethoxy-l,3,4,6,7,llb-hexahydro-pyrido[2,l-a]isoquinolin-2-one (14) under the standard Bucherer-Lieb variation in a 2 1 water-ethanol solution (15a 15b = 8 l). ... 

As we have seen previously, succinimides containing a quaternary carbon form the basis for a series of anticonvulsant drugs. In the course of research in this series, it was found that the inclusion of additional hetero atoms in the ring was quite compatible with anticonvulsive activity. We consider here the oxa-zolidinediones a discussion of the hydantoins is found later in this section. 

HYDANTOINS Fhenytoin is the most commonly prescribed anticonvulsant because of its effectiveness and relatively low toxicity. However, a genetically linked inability to metabolize phenytoin has been identified. For this reason, it is important to monitor serum concentrations of the drug on a regular basis to detect signs of toxicity Fhenytoin is administered orally and parenterally. If the drug is administered parenterally, the IV route is preferred over the intramuscular route because erratic absorption of phenytoin causes pain and muscle damage at the injection site... 

Hydantoins are well-known anticonvulsant agents and as such have found extensive use in the treatment of epilepsy. Replacement of one of the carbonyl groups by thiocarbonyl is consistent with anticonvulsant activity. Thus, condensation of the ethyl ester... 

The Working Group on Status Epilepticus recommends that phenobar-bital be given after a BZ plus phenytoin has failed. Most practitioners agree that phenobarbital is the long-acting anticonvulsant of choice in patients with hypersensitivity to the hydantoins or in those with cardiac conduction abnormalities. 

Hydantoin analogs in this series 72) were prepared. Most of these compounds, however, were found less active as anticonvulsants than the corresponding phenyl derivatives. Only a few were found to have the same order of activity as 5,5-diphenylhydantoin. 

Drugs that may be affected by aspirin include ACE inhibitors, acetazolamide, anticoagulants, anticonvulsants (hydantoins, valproic acid), beta blockers, diuretics, methotrexate, NSAIDs, oral hypoglycemics, and uricosuric agents (probenecid, sulfinpyrazone). 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

Merritt and Putnam use screening to identify hydantoins as anticonvulsants Chain and Florey introduce manufactured penicillin... 

Alkylation of the hydantoin (89-2) from benzaldehyde with ethyl iodide takes place at the imide nitrogen to afford ethitoin (89-3) [93]. In much the same vein, treatment of the hydantoin (89-5) from propiophenone with methyl iodide (89-5) in the presence of a base affords mephenytoin (89-6) [94]. Replacement of the quite acidic imide proton by an aUcyl group is not required for activity the well-known anticonvulsant phenytoin (89-8) consists of simply the hydantoin obtained from benzophenone (89-7) [95] this is often formulated as its sodium salt. 

A somewhat different scheme is used for the preparation of an all-aliphatic thio-hydantoin. Thus, reaction of racemic leucine (91-1) with allylisothiocyanate (91-2) leads to the thiourea (91-3). Attack of the anion from treatment of that intermediate with a strong base leads to ring closure and the formation of the imidazoline ring. There is thus obtained the anticonvulsant agent albutoin (91-4) [97]. 

Derivatives of hydantoin, which has anticonvulsant activity, have been prepared by Mikolajczyk and co-workers,52 using PTC. The yield is almost quantitative. The selectivity is reversed, compared to the same reaction carried out in DME (dimethoxyethane). 

The action of 44 appears to be similar to that of the anticonvulsant diphenyl-hydantoin (45). Attempts have been made66) to correlate the stereochemical and biological features of 44 with those of chemically different anticonvulsants such as diphenylhydantoin, diazepam, procyclidine, trihexyphenidyl, and ethylphen-acemide. 

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