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| Clinical data | |
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| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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| Pharmacokinetic data | |
| Protein binding | Not significant |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.003.726 |
| Chemical and physical data | |
| Formula | C7H11NO3 |
| Molar mass | 157.169 g·mol−1 |
| 3D model (JSmol) | |
| Chirality | Racemic mixture |
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Paramethadione (brand nameParadione) is ananticonvulsant drug of the chemical class calledoxazolidinediones developed by the Illinois-based pharmaceutical companyAbbott Laboratories (known asAbbVie since January 1, 2013[1]), and approved by theFood and Drug Administration in 1949 for the treatment ofabsence seizures, also calledpartial seizures.[2][3]
In 1960, the yearly cost for 900 mg/day paramethadione was approximately $66,[4] which would translate to $462 yearly in 2007 (with CPI inflation) if paramethadione was still sold.[5]
Paramethadione acts to reduce T-type calcium currents in thalamic neurons which has been proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) duringabsence seizures.[6][7]
Paramethadione is associated with various adverse effects including sedation, increased visual sensitivity to light, GI distress, edema, nephropathy, neutropenia, myasthenia gravis-like syndrome, fatal aplastic anemia, and severe birth defects known asfetal trimethadione syndrome (orparamethadione syndrome).[8][9]
Paramethadione (brand name Paradione) was originally approved by theU.S. Food and Drug Administration (FDA) in 1949, as a second-line treatment forpetit mal andabsence seizures.[10] Paramethadione was ultimately discontinued in 1994 due to safety and efficacy concerns,[11][12] such as being associated withfetal trimethadione syndrome, which is also known asparamethadione syndrome.[13]
Paramethadione was first patented in 1949 byAbbott Laboratories[14] Abbott Labbortories continued to hold the patent to paramethadione until the approval was withdrawn in 2004 due to the drug no longer being in use.[15]
In the 1940strimethadione (brand nameTridione) was the only available treatment for absence seizures. However, while effective, this drug presented with significant adverse effects, which led to the search for an equally effective analog. While limited information is available from the time, a pre-market clinical study found that paramethadione, an analog of trimethadione, was not quite as effective at alleviating seizures as trimethadione, however, it did have a significantly lower side effect profile in 85 patients over the course of 2 years.[16] Notably, 80% of patients still showed a good response to paramethadione.[17]
Paramethadione, 5-ethyl-3,5-dimethyloxazolidine-2,4-dione, differs fromtrimethadione only in the substitution of one methyl group with an ethyl group. It is synthesized in a completely analogous manner, except that it comes from 2-hydroxy-2-methylbutyric acid instead of 2-hydroxyisobutyric acid.[14]
