Paramethadione (brand name Paradione) is an

anticonvulsant Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of b ...

in the oxazolidinedione class developed by the Illinois-based pharmaceutical company

Abbott Laboratories Abbott Laboratories is an American multinational medical devices and health care company with headquarters in Abbott Park, Illinois, United States. The company was founded by Chicago physician Wallace Calvin Abbott in 1888 to formulate known dr ...

(known as

AbbVie AbbVie is an American publicly traded biopharmaceutical company founded in 2013. It originated as a spin-off of Abbott Laboratories. History On October 19, 2011, Abbott Laboratories announced its plan to separate into two publicly traded compan ...

since January 1, 2013 ), and approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

in 1949 for the treatment of

absence seizures Absence seizures are one of several kinds of generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizures are characterized by ...

, also called

partial seizures Focal seizures (also called partial seizures and localized seizures) are seizures which affect initially only one hemisphere of the brain. The brain is divided into two hemispheres, each consisting of four lobes – the frontal, temporal, parie ...

. In 1960, the yearly cost for 900 mg/day paramethadione was approximately $66, which would translate to $462 yearly in 2007 (with CPI inflation) if paramethadione was still sold.

Mechanism of Action

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) during

Adverse Effects

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 as fetal trimethadione syndrome (or paramethadione syndrome).

History, society, and culture

FDA approval

Paramethadione (brand name Paradione) was originally approved by the

U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

(FDA) in 1949, as a second-line treatment for

petit mal Absence seizures are one of several kinds of Generalized epilepsy, generalized seizures. These seizures are sometimes referred to as petit mal seizures (from the French for "little illness", a term dated in the late 18th century). Absence seizure ...

and

. Paramethadione was ultimately discontinued in 1994 due to safety and efficacy concerns, such as being associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.

Patents

Paramethadione was first patented in 1949 by

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.

Clinical Trials

In the 1940s

trimethadione Trimethadione (Tridione) is an oxazolidinedione anticonvulsant. It is most commonly used to treat epileptic conditions that are resistant to other treatments. It is primarily effective in treating absence seizures, but can also be used in ref ...

(brand name Tridione) 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. Notably, 80% of patients still showed a good response to paramethadione.

Chemistry

Paramethadione, 5-ethyl-3,5-dimethyloxazolidine-2,4-dione, differs from

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.

References

External links

* * {{Anticonvulsants Oxazolidinediones AbbVie brands