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Pathway Description
Paramethadione Action Pathway
Homo sapiens
Drug Action Pathway
Paramethadione is an anticonvulsant in the oxazolidinedione class. It is associated with fetal trimethadione syndrome, which is also known as paramethadione syndrome. It is used for the control of absence (petit mal) seizures that are refractory to treatment with other medications. 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). Dione anticonvulsants such as paramethadione reduce T-type calcium currents in thalamic neurons (including thalamic relay neurons). This inhibits corticothalamic transmission and raises the threshold for repetitive activity in the thalamus. This results in a dampening of the abnormal thalamocortical rhythmicity proposed to underlie the 3-Hz spike-and-wave discharge seen on electroencephalogram (EEG) during absence seizures. Paramethadione is associated with various adverse effects including sedation, increased visual sensitivity to light, GI distress, edema, nephropathy, neutropenia, myasthenia gravis-like syndrome, fatal aplastic anemia, and severe birth defects known as fetal trimethadione syndrome. Paramethadione is administered as an oral tablet.
References
Paramethadione Pathway References
Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037.
Pubmed: 29126136
Di Pietro F, Macey PM, Rae CD, Alshelh Z, Macefield VG, Vickers ER, Henderson LA: The relationship between thalamic GABA content and resting cortical rhythm in neuropathic pain. Hum Brain Mapp. 2018 May;39(5):1945-1956. doi: 10.1002/hbm.23973. Epub 2018 Jan 17.
Pubmed: 29341331
Smith KA, Bierkamper GG: Paradoxical role of GABA in a chronic model of petit mal (absence)-like epilepsy in the rat. Eur J Pharmacol. 1990 Jan 25;176(1):45-55. doi: 10.1016/0014-2999(90)90130-x.
Pubmed: 1690139
Schulman J: Epileptic seizures controlled with paramethadione/primidone. Vet Med Small Anim Clin. 1981 Jun;76(6):827.
Pubmed: 6911910
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