Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures.
Additional recommended knowledge
Zonisamide was discovered by Uno and colleagues in 1972 and launched by Dainippon Sumitomo Pharma (大日本住友製薬, Dainippon Sumitomo Seiyaku?) (formerly Dainippon Pharmaceutical (大日本製薬, Dainippon Seiyaku?)) in 1989 as Excegran in Japan. It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai (エーザイ, Eisai?) in 2004. Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others) and Europe (starting in Germany and the United Kingdom).
Zonisamide is approved in the United States, United Kingdom, for adjunctive treatment of partial seizures in adults and in Japan for both adjunctive and monotherapy for partial seizures (simple, complex, secondarily generalized), generalized (tonic, tonic-clonic (grand mal), and atypical absence) and combined seizures.
An open trial on zonisamide in seven Parkinson's disease patients had positive results, according to this 2001 report. Since then, it has been reported to treat the resting tremor that other therapies may leave behind. By early November of 2005, Dainippon Sumitomo had filed a NDA for the use of zonisamide in Parkinson's disease; it is to be marketed as Tremode.
It has also been studied for obesity with significant positive effects on body weight and there are three ongoing clinical trials for this indication.
Zonisamide has been studied for and used as a migraine preventative medication, and has also been shown to be effective in some cases of neuropathic pain. It has also been used by psychiatrists as a mood stabilizer.
Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5, to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.
Mechanism of action
The exact mechanism of action is not known for zonisamide. According to Leppik, while zonisamide may be a carbonic anhydrase inhibitor like acetazolamide, this is not one of the primary mechanisms of action, which might be blocking repetitive firing of voltage-gated sodium channels and reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors like the benzodiazepines and muscimol,, or increasing the levels of the glutamate transport protein in the brain while decreasing the amount of GABA transport protein, in other words, inhibiting the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.
The most common side effects include drowsiness, loss of appetite, dizziness, headache, nausea, and agitation/irritability.
Zonisamide and other carbonic anhydrase inhibitors such as topiramate, furosemide, and hydrochlorothiazide have been known to interfere with amobarbital, which has led to inadequate anesthetization during the Wada test.
Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine in descending order.
References and end notes
- ^ Shah, Jaymin; Kent Shellenberger, Daniel M. Canafax  (2002-06-15). "Zonisamide", in René H. Levy, Richard H. Mattson, Brian S. Meldrum, and Emilio Perrucca (ed.): Antiepileptic Drugs, Fifth, Philadelphia: Lippincott Williams
& Wilkins, 873. ISBN 0-7817-2321-3.
- ^ Dainippon Sumitomo Pharma Co., Ltd. (2005). Company History. Company Information. Dainippon Sumitomo Co., Ltd.. Retrieved on 12 November, 2005.
- ^ Dainippon Pharmaceutical Co., Ltd. (2004). Transfer of Rights Agreement for North America and Europe Reached on Zonegran. News Releases for Dainippon Pharmaceutical in 2004. Dainippon Sumitomo Pharma Co., Ltd. Retrieved on 12 November, 2005.
- ^ Dainippon Pharmaceutical Co., Ltd. (2005). Dainippon Pharmaceutical and Eisai Conclude Agreement for the Development, Manufacture and Marketing of the Anti-Epileptic Agent Zonisamide in Asia. Dainippon Pharmaceutical News Releases for 2005. Dainippon Sumitomo Pharma Co., Ltd.. Retrieved on 12 November, 2005.
- ^ Eisai Co., Ltd. (2005). Eisai Announces Launch of Zonegran (zonisamide), Treatment For Epilepsy In the UK and Germany. Eisai 2005 News Releases. Eisai Co., Ltd.. Retrieved on 12 November, 2005.
- ^ Élan Pharmaceuticals Inc (2003). NDA 20-789/S-001; Zonegran (zonisamide) Capsules 25, 50, 100 mg FDA Approvable Labeling Text - August 22 2003 (PDF). Zonisamide Approval History. Food and Drug Administration. Retrieved on 2005-11-13.
- ^ Eisai Ltd. (2005). Zonegran Summary of Product Characteristics. electronic Medicines Compendium. Medicines.org.uk. Retrieved on 2005-11-13.
- ^ Dainippon Pharmaceutical Co., Ltd. (2004). EXCEGRAN Tablets 100 mg & EXCEGRAN Powder 20% (English). Retrieved on 2006-03-13.
- ^ Murata, Miho; Horiuchi Emiko and Kanazawa Ichiro (December 2001). "Zonisamide has beneficial effects on Parkinson's disease patients". Neuroscience Research 41 (4): 397–9. PubMed.
- ^ Nakanishi, I; Kohmoto J, Miwa H, Kondo T (August 2003). "[Effect of zonisamide on resting tremor resistant to antiparkinsonian medication]". No To Shinkei 55 (8): 685–9. PubMed.
- ^ Dainippon Sumitomo Pharma Co., Ltd. (2005). New Drugs in the R&D Pipeline (under development by DSP) (PDF). List of Product Development Project. Retrieved on 2005-11-21.
- ^ Gadde, Kishore M.; Deborah M. Franciscy, H. Ryan Wagner, II; K. Ranga R. Krishnan (April 2003). "Zonisamide for Weight Loss in Obese Adults: A Randomized Controlled Trial". Journal of the American Medical Association 289 (14): 1820–1825. PubMed.
- ^ University of Cincinnati (2005). Zonegran in the Treatment of Binge Eating Disorder Associated With Obesity. ClinicalTrials.gov. Retrieved on 2006-05-04.
- ^ Tuscaloosa Research & Education Advancement Corporation (2005). Zonegran for the Treatment of Weight Gain Associated With Psychotropic Medication Use: A Placebo-Controlled Trial. ClinicalTrials.gov. Retrieved on 2006-05-04.
- ^ National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (2006). Zonisamide for Weight Reduction in Obese Adults. ClinicalTrials.gov. Retrieved on 2006-05-04.
- ^ Dr. Brian D. Loftus (2004). Zonegran. Retrieved on 2006-11-29.
- ^ Hasegawa, Hisanori (May 2004). "Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital". Curr Med Research Opinion 20 (5): 577–580. PubMed.
- ^ Ohmori, S.; Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, Kitada M (1998 May 8). "Differential catalytic properties in metabolism of endogenous and exogenous substrates among CYP3A enzymes expressed in COS-7 cells". Biochimica et Biophysica Acta 1380 (3): 297-304. PubMed.
- ^ Stiff, D. D.; Robicheau JT, Zemaitis MA. (January 1992). "Reductive metabolism of the anticonvulsant agent zonisamide, a 1,2-benzisoxazole derivative". Xenobiotica 22 (1): 1-11. PubMed.
- ^ Leppik, Ilo E. (December 2004). "Zonisamide: chemistry, mechanism of action, and pharmacokinetics". Seizure 13 (Suppl 1): S5-9; discussion S10. doi:10.1016/j.seizure.2004.04.016. PubMed.
- ^ Mimaki, T.; Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (March 1990). "Interaction of zonisamide with benzodiazepine and GABA receptors in rat brain". Medical Journal of Osaka University 39 (1-4): 13-7. PubMed.
- ^ Mimaki, T.; Suzuki Y, Tagawa T, Karasawa T, Yabuuchi H (1990 March). "[3H]zonisamide binding in rat brain". Medical Journal of Osaka University 39 (1-4): 19-22. PubMed.
- ^ Ueda, Yuto; Doi Taku, Tokumaru Jun, and L. James Willmore (2003 August 19). "Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures". Molecular Brain Research 116 (1-2): 1-6. doi:10.1016/S0169-328X(03)00183-9. PubMed.
- ^ Bookheimer, Susan; Schrader, Lara M.; Rausch, Rebecca; Sankar, Raman; Engel, Jerome Jr. (February 2005). "Reduced anesthetization during the intracarotid amobarbital (Wada) test in patients taking carbonic anhydrase-inhibiting medications". Epilepsia 46 (2): 236. doi:10.1111/j.0013-9580.2005.23904.x.
- ^ Nakasa, H.; Nakamura H, Ono S, Tsutsui M, Kiuchi M, Ohmori S, Kitada M. (April 1998). "Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data". European Journal of Clinical Pharmacology 54 (2): 177–83. PubMed.
|Barbiturates||Barbexaclone, Metharbital, Methylphenobarbital, Pentobarbital, Phenobarbital, Primidone|
|Hydantoins||Ethotoin, Fosphenytoin, Mephenytoin, Phenytoin|
|Oxazolidinediones||Ethadione, Paramethadione, Trimethadione|
|Succinimides||Ethosuximide, Mesuximide, Phensuximide|
|Benzodiazepines||Clobazam, Clonazepam, Clorazepate, Diazepam, Lorazepam, Midazolam, Nitrazepam, Temazepam|
|Carboxamides||Carbamazepine, Oxcarbazepine, Rufinamide|
|Fatty acid derivatives||Valpromide, Valnoctamide|
|Carboxylic acids||Valproic acid (Sodium valproate & Valproate semisodium), Tiagabine|
|Others||GABA analogs: Gabapentin, Pregabalin, Progabide, Vigabatrin -- Monosaccharides: Topiramate -- Aromatic allylic alcohols: Stiripentol -- Ureas: Phenacemide, Pheneturide -- Phenyltriazines: Lamotrigine
Carbamates: Emylcamate, Felbamate, Meprobamate -- Pyrrolidines: Brivaracetam, Levetiracetam, Nefiracetam, Seletracetam
Sulfa drugs: Acetazolamide, Ethoxzolamide, Sultiame, Zonisamide -- Propionates: Beclamide -- Aldehydes: Paraldehyde -- Bromides: Potassium bromide, Sodium bromide