Zonisamide
CAS: 68291-97-4
Appearance: white crystal powder
Description:
Broad spectrum antibiotic. GABA receptor agonist. Anticonvulsant, pharmacological profile similar to carbamazepine.Zonisamide active in hypomania in early stage. Slowly but almost completely absorbed. The plasma proteins binding is approximately 40-60%. In adults, the elimination T 1/2 is 50-62 hrs and the steady-state is only achieved after 2 weeks. The dos-serum level correlation is linear up to doses of 10-15mg/day. A suppository form is studied. Although not definitely proved, zonisamide may induce psychotic episodes with an higher risk in young patients. It is recommended in such cases to terminate the zonisamide treatment as soon as possible and never restart it.
References:
1¡¢Fisher R, Blum D: Clobazam, oxcarbazepine, tiagabine, topiramate, and other new antiepileptic drugs. Epilepsia 36 (suppl 2): S105-S114, 1995
2¡¢Shinoda M, Akita M, Hasegawa M & al: The necessity of adjusting the dosage of zonisamide when coadministered with other anti-epileptic drugs. Bio Pharm Bull 19/8: 1090 - 1092, 1996
3¡¢Perucca E, Bialer M: The clinical pharmacokinetics of the newer antiepileptic drugs. Focus on topiramate, zonisamide and tiagabine. Clin Pharmacokin 31/1: 29-46, 1996 - Shimoyama R, Ohkubo T, Sugawara K: Monitoring of zonisamide in human breast milk and maternal plasma by solid-phase extraction HPLC method. Biomed Chromatogr 13/5: 370-372, 1999
4¡¢Miyamoto T, Kohsaka M, Koyama T: Psychotic episodes during zonisamide treatment. Seizure 9/1: 65-70, 2000.
Zonegran or Zonisamide is one of the newer anti-epiletic drugs (AEDs). It comes as a single sized tablet of 100 mg. The medication has a very long half-life (measured in days, not hours) and therefore appropriate for one time daily dosing. It is the only new AED that is indicated for once daily dosing.
The medication has multiple mechanisms of action, the relative importance of each to its anti-epileptic effect is not known. Mechanisms include blocking sodium (Na+) channels, reducing voltage-dependent, transient inward T-type calcium (Ca++) channels, increasing GABA release, blocking potassium (K+) evoked glutamate-mediated synaptic excitation, and weakly inhibiting carbonic annhydrase. It is considered effective in partial onset seizures. It does not appear to cause any bone marrow problems. Its incidence of liver toxicity is much lower than the older AEDs. It can cause renal stones. It is in the sulfa family of drugs and therefore should not be used by patients allergic to sulfa drugs. The medication should be discontinued in patients who develop a rash. The medication does not interfere with birth control pills. Its safety in pregnancy is not known. There are drug interactions with other AEDs.
In open label trials, Zonegran? has been shown effective in reducing the number of migraines. It is currently being studies in a placebo controlled fashion.
In open label add on trials, Zonegran? has been shown to be effective in some forms of neuropathic pain.
A very exciting recent placebo-controlled trial published in JAMA April 9, 2003 issue by Kishore Gadde, M.D. et. al., demonstrated a significant weight loss in obese patients taking zonegran at a dose of at least 400 mg per day. At 32 weeks, the average patient demonstrated a 9.4% weight loss. They lost on average 4 inches in the waist. Patients lost weight in week 16 to 32 (although at a slower rate than week 0- 16 ) so the final weight loss is not known. This data adds to other data seen in epilepsy patients which found weight loss as well. At least one study suggested that females were more likely to lose weight than males.
Zonisamide has been used by psychiatrists as a mood stabilizing medication. This topic is beyond the scope of this web site.
