Antiabsence activity

Likewise, animal models characteristically discern three types of activity activity against electrically induced convulsions correlates with activity again.st generalized tonic-clonic and partial seizures, and activity against penty-Icnetetrazole (PTZ)-induced. seizures correlates with antiabsence activity. Of late, a fourth model, activity against pilocarpine and kainic acid seizures, is said to predict protection against temporal lobe epilep.sy (a complex partial seizure). 

The compounds have a trophism toward antigencralized loDic-donic rather than antiabsence activity. This is not an inuinsic activity of the hydantoin ring. system. All of the cGnically useful antigeneralized tonic-clonic compounds liable 14-4) possess an aryl suKstituent on the S position, conesponding to the branched atom of the general pharma-to )hore. Hydantoins with lower alkyl sub.stituents report- ily have antiabsence activity. 

Phensuximide, USP. Some trophism toward antiabsence activity is attributed to the succinimide system. The -CHi- could be viewed as an a-alkyl branch condensed into the ring. Phensuximide. A(-melhyl-2-phenylsuccinimidc (Milontin), is used primarily against absence seizures, hut it has low potency and is relegated to secondary status. The... 

Ethosuximide, USE. Ethosuximide. 2-ethyl-2-methyl succinimide (Zarontin), conforms very well to the general structural pattern for antiabsence activity. The drug is more active and less toxic than trimelhadione. It is a calcium T channel-blocking drug. Toxicity primarily involves the. skin and blood. 

A certain portion of the drug is excreted intact through the kidney. However, the major metabolite is aetually produeed by oxidation of the ethyl group. It conforms quite closely to the general structural pattern for the antiabsence activity . It is observed to be much more active and comparatively less toxic than trimethadione. Therefore, it has gained cognizance as a drug of choice for acute absence seizures. 

Phensuximide and methsuximide are phenylsuccinimides that were developed and marketed before ethosuximide. They are used primarily as antiabsence drugs. Methsuximide is generally considered more toxic, and phensuximide less effective, than ethosuximide. Unlike ethosuximide, these two compounds have some activity against maximal electroshock seizures, and methsuximide has been used for partial seizures by some investigators. 

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