Paramethadione

Source: Wikipedia, the free encyclopedia.
Paramethadione
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
ATC code
Pharmacokinetic data
Protein bindingNot significant
Identifiers
  • (RS)-5-Ethyl-3,5-dimethyl-oxazolidine-2,4-dione
JSmol)
ChiralityRacemic mixture
  • O=C1N(C(=O)OC1(C)CC)C
  • InChI=1S/C7H11NO3/c1-4-7(2)5(9)8(3)6(10)11-7/h4H2,1-3H3 checkY
  • Key:VQASKUSHBVDKGU-UHFFFAOYSA-N checkY
  (verify)

Paramethadione (brand name Paradione) is an

partial 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]

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

absence seizures.[6][7]

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

History, society, and culture

FDA approval

Paramethadione (brand name Paradione) was originally approved by the

Patents

Paramethadione was first patented in 1949 by Abbott Laboratories[14] Abbott Labbortories continued to hold the patent to paramethadione until the approval was withdrawn in 2004 due to the drug no longer being in use.[15]

Clinical Trials

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.[16] Notably, 80% of patients still showed a good response to paramethadione.[17]

Chemistry

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.[14]

References

  1. ^ More than splitting pills: Health care giant Abbott Laboratories ready to spin off AbbVie - Retrieved November 7, 2016
  2. ^ "Oxazolidinedione Anticonvulsants". drugs.com.
  3. ^ Sittig M (2015). Pharmaceutical manufacturing encyclopedia. New York: William Andrew Pub.
  4. ^ Lennox WG (1960). Epilepsy and related disorders. Boston: Little Brown.
  5. PMID 19298435
    .
  6. ^ "Paramethadione". Drug Bank.
  7. PMID 8392750
    .
  8. .
  9. ^ Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes - Retrieved January 2007.
  10. ^ Miller RR, Greenblatt DJ (1979). Handbook of Drug Therapy. New York: Elsevier North Holland. p. 597.
  11. ^ Drug information for PARADIONE
  12. PMID 19298435
    .
  13. ^ Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes - Retrieved January 2007.
  14. ^ a b US 2575693, Spielman MA, published 1951 
  15. ^ Schering Corp.; et al. (2004). Withdrawal of Approval of 92 New Drug Applications and 49 Abbreviated New Drug Applications (Report). DEPARTMENT OF HEALTH AND HUMAN SERVICES: Food and Drug Administration. p. 25125. Docket No. 2004N-0159.
  16. .
  17. .

External links

  • Diseases Database (DDB): 33106
  • Hoffman DJ, Chun AH (October 1975). "Paramethadione and metabolite serum levels in humans after a single oral paramethadione dose". Journal of Pharmaceutical Sciences. 64 (10): 1702–3.
    PMID 1185541
    .