Zonisamide blocks voltage-dependent sodium and calcium channels and may reduce presynaptic glutamate release (Mac Donald 2002). Furthermore an increase in dopamine and serotonin levels in striatal and hippocampal structures are reported (Kaneko and others 1993, Okada and others 1995). It has a half-life of about 15 hours in dogs (Matsumoto and others 1983, Thomas 2003). Most is excreted unchanged in urine although some hepatic metabolism occurs.

Indications
Adjunct therapy for canine seizures refractory to standard medication.

Dose
An initial dose rate of 5 to 10 mg/kg BID is recommended - aiming for a serum concentration of 10-40 ug/ml.

Side effects
Zonisamide appears to be safe - few side-effects are reported in dogs, although mild ataxia and sedation may occur when treatment is started and vomiting and loss of appetite have been reported in some dogs (Dewey and others, 2004).

Has caused kidney stones in some people.

At a dose of 75 mg/kg bodyweight (four times the recommended dose) slight changes in blood count and an increase of liver weight were observed in one study (Walker and others 1988).

References

von Klopmann T, Rambeck B, Tipold A (2007) A study of zonisamide therapy for refractory idiopathic epilepsy in dogs. JSAP 48

Boothe D M, Perkins J, Dewey C. (2005) Clinical pharmacokinetics and safety of the anticonvulsant zonisamide in healthy dogs following single and multiple dosing. In: Proceedings of the 23rd ACVIM forum, Baltimore, USA. pp 858

Dewey C W, Guiliano R, Boothe D M, Berg J M, Kortz G D, Joseph R J, Budsberg S C (2004) Zonisamide therapy for refractory idiopathic epilepsy in dogs. Journal of the AmericanAnimalHospital Association 40, 285-291 PubMed.

Hamada K, Song H K, Ishida S, Yagi K, Seino M (2001) Contrasting effects of zonisamide and acetazolamide on amygdaloid kindling rats. Epilepsia 42, 1379-1386 PubMed.

Kaneko S, Okada M, Hirano T (1993) Carbamazepine and zonisamide increase extracellular dopamine and serotonin levels in vivo, and carbamazepine does not antagonize adenosine effect in vitro: mechanisms of blockade of seizure spread. Japanese Journal of Psychiatry and Neurology 47, 371-373 PubMed.

Mac Donald R L (2002) Zonisamide. In: Antiepileptic drugs. 5th edn. Eds: R H Levy, R H Mattson, B S Meldrum, E Perucca. Lippincott Williams and Wilkens, Philadelphia. pp 867-898

Matsumoto K, Miyazaki H, Fujii T, Kagemoto A, Maeda T, Hashimoto M (1983) Absorption, distribution and excretion of 3-(sulfamoyl[14C]methyl)-1,2-benziosoxazole (AD-810) in rats, dogs and monkeys and of AD-810 in men. Drug Research 33, 961-968 PubMed.

Okada M, Kaneko S, Hirano T (1995) Effects of zonisamide on dopaminergic system. Epilepsy Research 22, 193-205 PubMed.

Saito M, Orito K, Takikawa S, Kageyama T, Muto M (2005) Pharmacokinetics of zonisamide administered alone and in combination with phenobarbital in dogs. In: Proceedings of the 23rd ACVIM forum, Baltimore, USA. pp 858-859

Walker R M, DiFonzo C J, Barsoum N J, Smith G S, Macallum G E (1988) Chronic toxicity of the anticonvulsant zonisamide in beagle dogs. Fundamental and applied Toxicology 11, 333-342 PubMed.