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Primidone

  • Janet Mifsud
Reference work entry

Chemical Structure and When it was Licensed

Chemical name: 5-ethyldihydro-5-phenyl-4,6 (1H, 5H) pyrimidinedione.

The effectiveness of primidone in epilepsy was first demonstrated in 1949 (Whitty 1953). It was introduced a year later by the Imperial Chemical Industry (ICI) (now known as AstraZeneca) in the UK and Germany. In 1952, its effectiveness in the treatment of patients with idiopathic generalized epilepsy was demonstrated, and it was introduced in 1954 (as Mysoline®) by Wyeth in the USA (Williams 1956).

Mode of Action

Primidone has an anticonvulsant activity, as do its two main metabolites:  Phenobarbital and Other Barbiturates and phenylethylmalonamide (PEMA) (El-Masri and Portier 1998) ( Figs. 279-1 and 279-2). Primidone acts through interactions with voltage-gated sodium channels that inhibit high-frequency repetitive firing of action potentials (MacDonald and Kelly 1995).

Keywords

Megaloblastic Anemia Juvenile Myoclonic Epilepsy Idiopathic Generalize Epilepsy Oral Contraceptive Steroid Anticonvulsant Hypersensitivity Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Baciewicz AM (1986) Carbamazepine drug interactions. Ther Drug Monit 8:305–317CrossRefPubMedGoogle Scholar
  2. Bruno MK, Harden CL (2002) Epilepsy in pregnant women. Curr Treat Opt Neurol 4:3140Google Scholar
  3. El-Masri HA, Portier CJ (1998) Physiologically based pharmacokinetics model of primidone and its metabolites phenobarbital and phenylethylmalonamide in humans, rats, and mice. Drug Metab Dispos 26:585–594PubMedGoogle Scholar
  4. FDA (2009) Primidone official FDA information. http://www.fda.gov/cder/foi/label/2000/010401s013lbl.pdf (Accessed April 2009)
  5. Gatti G, Furlanut M, Perucca E (2001) Interindividual variability in the metabolism of anti-epileptic drugs and its clinical application. In: Pacifici GM, Pelkonen O (eds) Interindividual variability in human drug metabolism. CRC Press, Boca Raton, p 168Google Scholar
  6. Loiseau PJ (1999) Clinical experience with new antiepileptic drugs: antiepileptic drugs in Europe. Epilepsia 40(Suppl 6):S38CrossRefGoogle Scholar
  7. MacDonald RL, Kelly KM (1995) Antiepileptic drug mechanisms of action. Epilepsia 36(S2):S212CrossRefGoogle Scholar
  8. Madan A, Graham RA (2003) Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos 31:42131CrossRefGoogle Scholar
  9. Martinez C, Gatti G, Sasso E, Calzetti S, Perucca E (1990) The disposition of primidone in elderly patients. Br J Clin Pharmacol 30:60711Google Scholar
  10. Mattson RH, Cramer JA, Collins JF, Smith DB, Delgado-Escueta AV, Browne TR, Williamson PD, Treiman DM, McNamara JO, McCutchen CB et al. (1985) Comparison of carbamazepine, phenobarbital, phenytoin, and primidone in partial and secondarily generalized tonic-clonic seizures. NEJM 313:14551CrossRefGoogle Scholar
  11. Mehta KM (2008) British National Formulary. Pharmaceutical Press, London http://www.bnf.org
  12. Schlienger RG, Shear NH (1998) Antiepileptic drug hypersensitivity syndrome. Epilepsia 39(S7):S37Google Scholar
  13. Spina E, Perucca E (2002) Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. Epilepsia 43(S2):3744Google Scholar
  14. Thomas SV (2006) Management of epilepsy and pregnancy. Postgrad Med 52(1):57–64Google Scholar
  15. Whitty CW (1953) Value of primidone in epilepsy. BMJ 2(4835):5401CrossRefGoogle Scholar
  16. Williams D (1956) Treatment of epilepsy with mysoline. Proc R Soc Med 49:58991Google Scholar

Copyright information

© Springer-Verlag London Limited 2010

Authors and Affiliations

  • Janet Mifsud
    • 1
  1. 1.Department of Clinical Pharmacology and TherapeuticsUniversity of MaltaMsidaMalta

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