Metabolic Demethylation of 3,5,5-Trimethyl-2,4-Oxazolidinedione (Trimethadione, Tridione).

Butler, Thomas; Mahaffee, D D; Mahaffee, Collins

doi:10.3181/00379727-81-19907

Cited by 23 publications

(5 citation statements)

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Section: Oxazolidinedionesmentioning

confidence: 96%

“…The same metabolic product was formed from ethadione , and an analogous product was formed by dealkylation of paramethadione (Butler, 1955). These metabolites had a long plasma half-life (about 10 days or more in man), compared with the relatively short half-life of the parent compound (Butler, 1955). Thus, with the administration of daily doses of trimethadione to human subjects, the plasma levels of dimethadione continue to build up over a period of several weeks before equilibrium conditions are attained (Chamberlin et al, 1965).…”

Section: Oxazolidinedionesmentioning

confidence: 98%

See 1 more Smart Citation

Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

Glazko¹

1975

Epilepsia

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Section: Oxazolidinedionesmentioning

confidence: 96%

Section: Oxazolidinedionesmentioning

confidence: 98%

Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

Glazko¹

1975

Epilepsia

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“…Trimethadione is the most specific antagonist that is known towards seizures induced by pentylenetetrazole (leptazol; metrazole), and it is thought that this antagonism may provide a fundamental clue to the reason for the efficacy of trimethadione in petit mal epilepsy (101). In rats, dogs, and man trimethadione is completely demethylated to 5.5dimethyl-2,4-oxazolidinedione, which is devoid of anticonvulsant activity and is slowly excreted in the urine (67,68,166). The d-and Worms of 5-ethyl-3.5dimethyl-2,4-oxazolidinedione were excreted by mice at about the same rate, and no significant difference was found in the physiological activity of the enantiomorphs (69).…”

Section: Oh-mnoi P-(ch3)2nc6h4cocooh F Substitution In the Methylene ...mentioning

confidence: 99%

2,4-Oxazolidinediones

Clark-Lewis¹

1958

Chem. Rev.

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“…Phenobarbital, like diphenylhydantoin, is converted in dogs and man to an almost inactive derivative by hydroxylation in the para position of the phenyl group (7). On the other hand, trimethadione is N-demethylated in dogs and man to 5,5-dimethyl-oxazolidine-2, 4-dione (dimethadione, DMO) (4,13). However, in contrast to the hydroxylated derivatives of phenobarbital and diphenylhydantoin, demethylated trimethadione retains anticonvulsant activity and contributes to the total anticonvulsant effect of the parent drug (4), as will be discussed later.…”

Section: Role Of Absorption Distribution Biotransformation and Excrmentioning

confidence: 99%

Role of Pharmacological Factors in the Evaluation of Anticonvulsant Drugs

Woodbury

1969

Epilepsia

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SUMMARY The results presented in this paper clearly delineate the role of various pharmacological factors in the evaluation of anticonvulsant drugs. The absorption, distribution, biotransformation, and excretion of drugs determine the concentration that reaches the receptor and the duration of effect. Thus changes in any one of these parameters can modify greatly the quantitative evaluation of drugs. However, determination of these parameters can also increase our understanding of the mechanisms by which anticonvulsant drugs act. Complete delineation of their mechanisms of action is the goal of pharmacologists interested in this field and can lead to the discovery of new methods for evaluation of anticonvulsants and new drugs for the treatment of epilepsy. Various factors increase or decrease susceptibility of animals to seizures and must be rigidly controlled in experimental situations involving assay of anticonvulsant agents. RÉUMÉ Les résultats présentés dans cette communication définissent clairement le rôle de différents facteurs pharmacologiques dans ľévaluation de médicaments anticonvulsifs. La résorption, la distribution, la bio‐transformation et ľexcrétion ďun médicament déterminent la concentration qui atteint le récepteur et la durée des effets de ce médicament. Par conséquent, tout changement apportéàľun quelconque de ces paramètres peut modifier profondement ľévaluation quantitative ďun médicament. Toutefois, la détermination de ces parametres peut également nous faire mieux comprendre les mécanismes par lesquels les médicaments anticonvulsifs exercent leur action. Une définition complète de leurs mécanismes ďaction est ľobjectif que pour‐suivent les pharmacologues intéressés à ce domaine et elle peut aboutir à la découverte de nouvelles méthodes ďévaluation des anticonvulsifs et de médicaments nouveaux pour le traitement de ľépilepsie. Différents facteurs augmentent ou diminuent la sensibilite des animaux àľégard des convulsions et ces facteurs doivent être stricte‐ment contrôlés dans des situations expérimentales en rapport avec ľessai de médicaments anticonvulsifs.

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Metabolic Demethylation of 3,5,5-Trimethyl-2,4-Oxazolidinedione (Trimethadione, Tridione).

Cited by 23 publications

References 0 publications

Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

Antiepileptic Drugs: Biotransformation, Metabolism, and Serum Half‐Life

2,4-Oxazolidinediones

Role of Pharmacological Factors in the Evaluation of Anticonvulsant Drugs

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