Zonisamide

[Description]:

Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug.Target: Calcium channel inhibitor; Sodium channel inhibitorZonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure. Zonisamide is a 1,2 benzisoxazole derivative and the first agent of this chemical class to be developed as an antiepileptic drug. It has shown activity in various animal models of epilepsy, and although a detailed mode of action awaits clarification it appears to block the propagation/spread of seizure discharges and to suppress the epileptogenic focus [1].Zonisamide 500 mg/day was significantly superior to placebo in reducing the frequency of complex partial seizures (-51% versus -16%), all partial seizures and all seizures, with dose-dependent benefit provided over a 100-500 mg/day dose range. Supporting trials have confirmed significant increases in reduction in median seizure frequency (up to 41%) and responder rates (35-42%) compared with placebo following zonisamide 400-600 mg/day, enabling 20-27% of patients to attain >or=75% reduction in seizure frequency [2].Clinical indications: Epilepsy; Lewy body dementia; Parkinsons diseaseToxicity: Anorexia; Somnolence; Dizziness; Irritability; Confusional state; Depression; Diplopia; Memory impairment

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Calcium Channel

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Neurological Disease

[References]

[1]. Peters DH, et al. Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. 1993 May;45(5):760-87.

[2]. Brodie MJ, et al. Zonisamide as adjunctive therapy for refractory partial seizures. Epilepsy Res. 2006 Feb;68 Suppl 2:S11-6. Epub 2005 Nov 28.

[Related Small Molecules]

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
457.2±47.0 °C at 760 mmHg

[ Melting Point ]:
275°C dec.

[ Molecular Formula ]:
C₈H₈N₂O₃S

[ Molecular Weight ]:
212.226

[ Flash Point ]:
230.3±29.3 °C

[ Exact Mass ]:
212.025558

[ PSA ]:
94.57000

[ LogP ]:
-0.10

[ Vapour Pressure ]:
0.0±1.1 mmHg at 25°C

[ Index of Refraction ]:
1.656

[ Water Solubility ]:
H2O: >5 mg/mL, soluble

Click to get detail MSDS

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DE4930000

CHEMICAL NAME :: 1,2-Benzisoxazole-3-methanesulfonamide

CAS REGISTRY NUMBER :: 68291-97-4

LAST UPDATED :: 199612

DATA ITEMS CITED :: 21

MOLECULAR FORMULA :: C8-H8-N2-O3-S

MOLECULAR WEIGHT :: 212.24

WISWESSER LINE NOTATION :: T56 BONJ D1SZW

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1992 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - ataxia

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 733 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,477,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 925 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - ataxia

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 672 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - ataxia

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1829 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4172896

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 699 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 30,477,1980

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1009 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - ataxia

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 816 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,600,1990

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Gastrointestinal - nausea or vomiting

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: >1 gm/kg

TOXIC EFFECTS :: Autonomic Nervous System - smooth muscle relaxant (mechanism undefined, spasmolytic) Behavioral - ataxia Gastrointestinal - nausea or vomiting

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4337,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 5200 mg/kg/30D-I

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4347,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 23400 mg/kg/39W-I

TOXIC EFFECTS :: Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4361,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 27375 mg/kg/52W-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 11,333,1988 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13 mg/kg

SEX/DURATION :: male 64 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Paternal Effects - testes, epididymis, sperm duct

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4387,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5160 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 15 day(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea) Reproductive - Fertility - other measures of fertility

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4387,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 220 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Effects on Newborn - behavioral Reproductive - Effects on Newborn - delayed effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4399,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 660 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - other postnatal measures or effects

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4399,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2500 mg/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4435,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 5 gm/kg

SEX/DURATION :: female 6-15 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4435,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1320 mg/kg

SEX/DURATION :: female 14-35 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4435,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1320 mg/kg

SEX/DURATION :: female 14-35 day(s) after conception

TOXIC EFFECTS :: Reproductive - Specific Developmental Abnormalities - cardiovascular (circulatory) system

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 15,4435,1987

[ Symbol ]:

GHS02, GHS06, GHS08

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H225-H301 + H311 + H331-H370

[ Precautionary Statements ]:
P210-P260-P280-P301 + P310-P311

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
R22

[ Safety Phrases ]:
7-16-36/37-45

[ RIDADR ]:
UN1230 - class 3 - PG 2 - Methanol, solution

[ WGK Germany ]:
3

[ HS Code ]:
2935009090

Click to get detail synthetic route

Precursor

DownStream

[ HS Code ]: 2935009090

[ Summary ]:
2935009090 other sulphonamides VAT:17.0% Tax rebate rate:9.0% Supervision conditions:none MFN tariff:6.5% General tariff:35.0%

Application of surfactant assisted dispersive liquid-liquid microextraction as an efficient sample treatment technique for preconcentration and trace detection of zonisamide and carbamazepine in urine and plasma samples.

J. Chromatogr. A. 1308 , 25-31, (2013)

A simple, rapid, and efficient method, based on surfactant assisted dispersive liquid-liquid microextraction (SA-DLLME), followed by high performance liquid chromatography (HPLC) has been developed fo...

Zonisamide in clinical practice.

Acta Neurol. Scand.,. Suppl.c. (194) , 29-35, (2012)

Zonisamide is currently licensed in Europe and the USA for the adjunctive treatment of partial seizures (with or without secondary generalization) in adults, based on the results of four pivotal, rand...

Zonisamide in the treatment of bulimia nervosa: an open-label, pilot, prospective study.

Int. J. Eat. Disord. 46(7) , 747-50, (2013)

To assess preliminarily the effectiveness of zonisamide in bulimia nervosa.This was an open-label, prospective, 12-week, flexible dose study of zonisamide in bulimia nervosa. The primary outcome was b...

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