Description
Phensuximide is an anticonvulsant. It inhibits seizures induced by maximal electroshock (MES) and pentylenetetrazole in mice (ED50s = 112 and 50 mg/kg, respectively). Phensuximide (1.25 mmol/kg, i.p.) induces proteinuria and hematuria in rats. Formulations containing phensuximide have been used in the treatment of petit mal seizures.
Originator
Milontin, Parke Davis, US ,1953
Uses
Phensuximide, like ethosuximide, is an anticonvulsant drug used in minor forms of
epilepsy.
Definition
ChEBI: Phensuximide is a member of pyrrolidines.
Manufacturing Process
10 grams of phenylsuccinic anhydride is dissolved in 250 ml of absolute ether and the solution is treated with dry methylamine until a precipitate ceases to form. After standing for ? hour the ether is decanted off and the residue iswashed with 40 ml of water by decantation. The mixture is filtered and the precipitate washed with 10 ml of water. By acidification of the filtrate, a white precipitate is obtained. After drying it weighs 8 grams and melts at 136°140°C. The two precipitates are combined and recrystallized from aqueous alcohol to give β-N-methylphenylsuccinamic acid which melts at 158°-160°C.
9 grams of β-N-methylphenylsuccinamic acid and 200 ml of acetyl chloride are heated together on a steam bath for ? hour. The excess acetyl chloride is removed by distillation and 50 ml of water are added to the thick residue. After allowing for hydrolysis of the excess acetyl chloride the water is decanted and the yellow residue dissolved in 75 ml of ether. The resulting solution is treated with charcoal twice and dried over anhydrous magnesium sulfate. On partial evaporation of the ether a white solid precipitates. There is obtained 4 grams of N-methyl-α-phenylsuccinimide which melts at 71°-73°C.
Brand name
Milontin (Parke-Davis).
Therapeutic Function
Anticonvulsant
Clinical Use
Phensuximide occasionally is used for the treatment of absence seizures refractory to other drugs, although it is considered to
be less effective than ethosuximide. It is excreted in both urine and bile, and it may cause harmless pink to red discoloration of
the urine. It should be used with caution in patients with acute intermittent porphyria.
Synthesis
Phensuximide, 1-methyl-3-phenylpyrrolidine-2,5-dione (9.3.5) is synthesized by the reaction of phenylsuccinic acid or its anhydride with methylamine [10,11].
Purification Methods
Crystallise phensuximide from hot 95% EtOH (m 72-73o). At 25o 1g of the imide dissolves in 1g of *C6H6, 18g of Et2O, 9.5g of EtOH, 5.1g of MeOH and 235g of H2O. [Beilstein 21 II 300, 21 III/IV 5465.]
