PARAMETHADIONE (500 MG)

Absorption

Rapid via the digestive tract.

Toxicity

Symptoms of overdose include clumsiness or unsteadiness, coma, severe dizziness, severe drowsiness, severe nausea, and problems with vision.

Originator

Paradione,Abbott, US ,1949

The Uses of PARAMETHADIONE (500 MG)

Paramethadione is also used in minor forms of epilepsy.

The Uses of PARAMETHADIONE (500 MG)

Paramethadione acts as an antiepileptic and anticonvulsant agent.

Background

Paramethadione is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome.

Indications

Used for the control of absence (petit mal) seizures that are refractory to treatment with other medications.

Definition

ChEBI: Paramethadione is an oxazolidinone.

Manufacturing Process

About 143.1 grams (one mol) of 5-methyl-5-ethyloxazolidine-2,4-dione is dissolved in 300 cc of methanol containing 23 grams of sodium. To the above mixture is added 126 grams of dimethyl sulfate in 10 cc portions while the temperature is maintained at about 50°C by external cooling. The mixture is then heated briefly to boiling, cooled, diluted with about 500 cc of water and extracted with two 250 cc portions of benzene. The benzene extract is separated, washed once with sodium bicarbonate solution and once with water. The benzene is removed by evaporation on a steam bath and the residue is fractionally distilled. The material boiling at 112° to 116°C at 25 mm pressure is taken; nD25=1.4495. Upon further fractionation, a very pure specimen boils at 101°-102°C at 11 mm.
The 5-methyl-5-ethyloxazolidine-2,4-dionemay be prepared by reacting methyl ethyl ketone with sodium cyanide and with ammonium thiocyanate followed by desulfurization. This intermediate may also be prepared by condensing α-hydroxy-α-methylbutyramide with ethyl chlorocarbonate or by condensing ethyl α-hydroxy-α-methylbutyrate with urea. Another method described (Traube and Aschar, Ber., 46, 2077-1913) consists in the condensation of ethyl α-hydroxy-α-methylbutyrate with guanidine followed by hydrolysis.

brand name

Paradione (Abbott).

Therapeutic Function

Anticonvulsant

Pharmacokinetics

Paramethadione is an oxazolidinedione anticonvulsant similar to trimethadione that acts on the central nervous system (CNS) to reduce the number of absence seizures (often seen in epileptics). Absence seizures involve an interruption to consciousness where the person experiencing the seizure seems to become vacant and unresponsive for a short period of time (usually up to 30 seconds). Paramethadione acts on thalamic neurons in the thalamic reticular nucleus (which studies have shown to be associated with absence seizures, von Krosigk et al., 1993).

Safety Profile

Moderately toxic by ingestion and intraperitoneal routes. Experimental teratogenic effects. Other experimental reproductive effects. Whenheated to decomposition it emits toxic fumes of NOx.

Synthesis

Paramethadione, 5-ethyl-3,5-dimethyloxazolidine-2,4-dione (9.8.3), differs from trimethadione only in the substitution of one methyl group with an ethyl group. It is synthesized in a completely analogous manner, except that it comes from 2-hydroxy-2-methylbutyric acid instead of 2-hydroxyisobutyric acid [29].

Metabolism

Primarily hepatic (mainly via cytochrome P450 isozyme 2C9), paramethadione is completely demethylated to 5-ethyl-5-methyl-2,4-oxazolidinedione, the active metabolite.