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Wilmington, North Carolina once had a thriving Black middle class and an elected interracial government. In 1898 white supremacists used violence to overthrow that government, kill Black residents and drive many others from the city.
MORE →Reflects the personal views, recollections, and perspective of the author, Mike Davis.
This is a personal recollection on the Move fire on May 13, 1985
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| Clinical data | |
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| Trade names | Zonegran, Zonisade |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a603008 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | ~100%[5] |
| Protein binding | 40%[5] |
| Metabolism | Liver through CYP3A4[5] |
| Elimination half-life | 63 hours in plasma[5] |
| Excretion | Kidney (62%); Faeces (3%)[5] |
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| PDB ligand | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.118.526 |
| Chemical and physical data | |
| Formula | C8H8N2O3S |
| Molar mass | 212.22 g·mol−1 |
| 3D model (JSmol) | |
| Melting point | 162 °C (324 °F) |
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Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease.[6][7] Chemically it is a sulfonamide. It is most commonly used as an anti-seizure medication in patients with focal or generalized epilepsy.
In 2020, it was the 276th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[8][9]
Zonisamide is approved in the United States,[2][10] United Kingdom,[11] Europe, Australia, Japan, South Korea and other countries as a treatment of focal epilepsy.[12] In the United States it is approved as an adjunctive therapy for patients with focal epilepsy aged 16 and older. However, in Europe, Japan, Australia and South Korea it is also approved for use as monotherapy in focal epilepsy.[13] There is also evidence that zonisamide is effective for the treatment generalized epilepsy (including absence, generalized tonic-clonic, myoclonic and other seizures types) in pediatric and adult patients.[12] Zonisamide has also been found to be safe and effective for patients with Lennox-Gastaut syndrome.
It has been approved for the treatment of the motor symptoms of Parkinson's disease (PD), as an adjunct to levodopa, in a few countries such as Japan.[6][7] In Japan, zonisamide has been used as an adjunct to levodopa treatment since 2009.[14] In addition, there is clinical evidence that zonisamide in combination with levodopa control of motor symptoms of PD but evidence for the treatment of the non motor symptoms of PD lacking.[6][15]
Zonisamide is sometimes used off label as a treatment for migraine headaches. Several small studies have suggested that it is effective and may work similarly to topiramate.[16]
Adverse effects by incidence:[5][17][18]
Very common (>10% incidence) adverse effects include:
Common (1–10% incidence) adverse effects include:
Incidence unknown
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.[20] Zonisamide may also interact with other carbonic anhydrase inhibitors to increase the potential for metabolic acidosis.[5]
Additionally, the metabolism of zonisamide is inhibited by ketoconazole, ciclosporin, miconazole, fluconazole and carbamazepine (in descending order of inhibition) due to their effects on the CYP3A4 enzyme.[21]
Zonisamide is not known to inhibit cytochrome P450 enzymes when present at therapeutic concentrations.[22]
Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and T-type calcium channels, which leads to the suppression of neuronal hypersynchronization (that is, seizure-form activity).[13] It is also known to be a weak carbonic anhydrase inhibitor (similarly to the anticonvulsant topiramate). In addition, zonisamide modulates GABAergic and glutamatergic neurotransmission.[13][23][24][25][26] More recently, it has also been demonstrated to positively modulate cerebral glycine receptors.[27]
Zonisamide has a variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8–3.9 hours. Bioavailability is close to 100% and food has no effect on the bioavailability of zonisamide, but may affect the rate of absorption.[28][22]
Zonisamide is metabolized mostly by the CYP3A4 isoenzyme, but also CYP3A7 and CYP3A5,[29] to 2-(sulphamoylacetyl)-phenol via reductive cleavage of the 1,2-benzisoxazole ring.[30]
Zonisamide was discovered by Uno and colleagues in 1972[31] and launched by Dainippon Sumitomo Pharma (formerly Dainippon Pharmaceutical) in 1989 as Excegran[32] It was marketed by Élan in the United States starting in 2000 as Zonegran, before Élan transferred their interests in zonisamide to Eisai Co., Ltd. in 2004.[33] Eisai also markets Zonegran in Asia (China, Taiwan, and fourteen others)[34] and Europe (starting in Germany and the United Kingdom).[35] It is available in the United States in capsules and an oral liquid preparation. In Europe and Japan it is also available as an orally dispersible tablet.[12]
In an open-label trial zonisamide attenuated the symptoms of tardive dyskinesia.[36]
It has also been studied for obesity[37] with significant positive effects on body weight loss and there are three ongoing clinical trials for this indication.[38][39][40]
It was a component of the never-marketed obesity treatment Empatic.[41]
It has also been used off-label by psychiatrists as a mood stabilizer to treat bipolar depression.[42][43]
Source: Wikipedia. Article content is retrieved live through the MediaWiki API.
Zonisamide, sold under the brand name Zonegran among others, is a medication used to treat the symptoms of epilepsy and Parkinson's disease. Chemically it is a sulfonamide. It is most commonly used as an anti-seizure medication in patients with focal or generalized epilepsy. In 2020, it was the 276th most commonly prescribed medication in the United States, with more than 1 million prescriptions.
Bupropion/zonisamide (former tentative brand name Empatic, Excalia) is an experimental combination of bupropion which was under development for the treatment of obesity. Bupropion is a norepinephrine–dopamine reuptake inhibitor and nicotinic acetylcholine receptor antagonist, while zonisamide is an anticonvulsant acting as a sodium channel blocker, T-type calcium channel blocker, and weak carbonic anhydrase inhibitor. The combination was being developed by Orexigen Therapeutics and reached phase II clinical trials prior to discontinuation.
1,2-Benzisoxazole is an aromatic organic compound with a molecular formula C7H5NO containing a benzene-fused isoxazole ring structure. The compound itself has no common applications; however, functionalized benzisoxazoles and benzisoxazoyls have a variety of uses, including pharmaceutical drugs such as some antipsychotics (including risperidone, paliperidone, ocaperidone, and iloperidone) and the anticonvulsant zonisamide. Its aromaticity makes it relatively stable; however, it is only weakly basic.
Carbonic anhydrase inhibitors are a class of pharmaceuticals that suppress the activity of carbonic anhydrase. Their clinical use has been established as anti-glaucoma agents, diuretics, antiepileptics, in the management of mountain sickness, gastric and duodenal ulcers, idiopathic intracranial hypertension, neurological disorders, or osteoporosis. Members of carbonic anhydrase inhibitor group of medications include: acetazolamide, sulthiame, zonisamide, topiramate, dorzolamide, methazolamide, brinzolamide, dichlorphenamide.
Before the 1921 destruction of Tulsa’s Greenwood District, Black residents had created a remarkable center of business and community life. The district included stores, professional offices, entertainment venues and homes owned by Black citizens. Understanding Greenwood means learning what was built—not only what was burned.
MORE →Mae Jemison, aboard Space Shuttle Endeavour in 1992.
