paramethadione

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 absence seizures.{{cite web | url = https://www.drugbank.ca/drugs/DB00617 | work = Drug Bank | title = Paramethadione }}{{cite journal | vauthors = von Krosigk M, Bal T, McCormick DA | title = Cellular mechanisms of a synchronized oscillation in the thalamus | journal = Science | volume = 261 | issue = 5119 | pages = 361–4 | date = July 1993 | pmid = 8392750 | doi = 10.1126/science.8392750 | jstor = 2881575 }}

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).{{cite book | vauthors = Miller RR, Greenblatt DJ |title=Handbook of Drug Therapy|year=1979|publisher=Elsevier North Holland|location=New York| isbn=978-0-444-00329-4}}[https://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?term=paramethadione+syndrome&field=name Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes] - Retrieved January 2007.

Paramethadione (brand name Paradione) was originally approved by the U.S. Food and Drug Administration (FDA) in 1949, as a second-line treatment for petit mal and absence seizures.{{cite book | vauthors = Miller RR, Greenblatt DJ |title=Handbook of Drug Therapy|date=1979|publisher=Elsevier North Holland|location=New York|page=597}} Paramethadione was ultimately discontinued in 1994 due to safety and efficacy concerns,[http://www.reference.md/files/PA/PARADIONE.html Drug information for PARADIONE]{{cite journal | vauthors = Shorvon SD | title = Drug treatment of epilepsy in the century of the ILAE: the second 50 years, 1959-2009 | journal = Epilepsia | volume = 50 Suppl 3 | issue = s3 | pages = 93–130 | date = March 2009 | pmid = 19298435 | doi = 10.1111/j.1528-1167.2009.02042.x | doi-access = free }} such as being associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.[https://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?term=paramethadione+syndrome&field=name Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes] - Retrieved January 2007.

Paramethadione was first patented in 1949 by Abbott Laboratories{{cite patent | inventor = Spielman MA | country = US | number = 2575693 | pubdate = 1951 }} 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.{{cite report|author=Schering Corp.|display-authors=etal|date=2004|title=Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications|url=https://www.federalregister.gov/documents/2004/05/05/04-10194/schering-corp-et-al-withdrawal-of-approval-of-92-new-drug-applications-and-49-abbreviated-new-drug|publisher=DEPARTMENT OF HEALTH AND HUMAN SERVICES: Food and Drug Administration|page=25125 |docket=Docket No. 2004N-0159}}

In the 1940s trimethadione (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.{{cite journal | vauthors = Davis JP, Lennox WG |date= 1949|title=A comparison of paradione and tridione in the treatment of epilepsy |journal=The Journal of Pediatrics|volume=34|issue=3 |pages=273–278|doi=10.1016/S0022-3476(49)80080-1}} Notably, 80% of patients still showed a good response to paramethadione.{{cite journal | vauthors = Drake FR | title = The current drug therapy of epilepsy: a review | journal = The American Journal of the Medical Sciences | volume = 230 | issue = 1 | pages = 98–107 | date = July 1955 | pmid = 14388023 | doi = 10.1097/00000441-195507000-00014 }}

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

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• {{DiseasesDB|33106}}
• {{cite journal | vauthors = Hoffman DJ, Chun AH | title = Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose | journal = Journal of Pharmaceutical Sciences | volume = 64 | issue = 10 | pages = 1702–3 | date = October 1975 | pmid = 1185541 | doi = 10.1002/jps.2600641027 }}

{{Anticonvulsants}}

Category:Oxazolidinediones

Category:Drugs developed by AbbVie