Anticonvulsant

Anticonvulsant
Drug class
Class identifiers
SynonymsAntiepileptic drugs, antiseizure drugs
UseEpilepsy
ATC codeN03
Biological targetBrain
Legal status
In Wikidata

Anticonvulsants (also known as antiepileptic drugs, antiseizure drugs, or anti-seizure medications (ASM)) are a diverse group of pharmacological agents used in the treatment of epileptic seizures.[1] Anticonvulsants are also increasingly being used in the treatment of bipolar disorder[2][3] and borderline personality disorder,[4] since many seem to act as mood stabilizers, and for the treatment of neuropathic pain.[5] Anticonvulsants suppress the excessive rapid firing of neurons during seizures.[6] Anticonvulsants also prevent the spread of the seizure within the brain.[7]

Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid (GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action.[8] Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptors, the GABA transporter type 1, and GABA transaminase.[9] Additional targets include voltage-gated calcium channels, SV2A, and α2δ.[10][11] By blocking sodium or calcium channels, antiepileptic drugs reduce the release of excitatory glutamate, whose release is considered to be elevated in epilepsy, but also that of GABA.[12] This is probably a side effect or even the actual mechanism of action for some antiepileptic drugs, since GABA can itself, directly or indirectly, act proconvulsively.[12] Another potential target of antiepileptic drugs is the peroxisome proliferator-activated receptor alpha.[13][14][15][16][17][18][19]

Some anticonvulsants have shown antiepileptogenic effects in animal models of epilepsy.[20] That is, they either prevent the development of epilepsy or can halt or reverse the progression of epilepsy. However, no drug has been shown in human trials to prevent epileptogenesis (the development of epilepsy in an individual at risk, such as after a head injury).[21]

  1. ^ Al-Otaibi F (1 September 2019). "An overview of structurally diversified anticonvulsant agents". Acta Pharmaceutica (Zagreb, Croatia). 69 (3). Walter de Gruyter GmbH: 321–344. doi:10.2478/acph-2019-0023. ISSN 1846-9558. PMID 31259739.
  2. ^ Joshi A, Bow A, Agius M (2019). "Pharmacological Therapies in Bipolar Disorder: a Review of Current Treatment Options". Psychiatria Danubina. 31 (Suppl 3): 595–603. ISSN 0353-5053. PMID 31488797.
  3. ^ Keck PE Jr, McElroy SL, Strakowski SM (1998). "Anticonvulsants and antipsychotics in the treatment of bipolar disorder". The Journal of Clinical Psychiatry. 59 (Suppl 6): 74–82. PMID 9674940.
  4. ^ American Psychiatric Association, and American Psychiatric Association. Work Group on Borderline Personality Disorder. Practice guideline for the treatment of patients with borderline personality disorder. American Psychiatric Pub, 2001.
  5. ^ Rogawski MA, Löscher W (2004). "The neurobiology of antiepileptic drugs". Nature Reviews Neuroscience. 5 (7): 553–564. doi:10.1038/nrn1430. PMID 15208697. S2CID 2201038. Archived from the original on 16 December 2020. Retrieved 20 September 2020.
  6. ^ McLean MJ, Macdonald RL (June 1986). "Sodium valproate, but not ethosuximide, produces use- and voltage-dependent limitation of high frequency repetitive firing of action potentials of mouse central neurons in cell culture". Journal of Pharmacology and Experimental Therapeutics. 237 (3): 1001–1011. PMID 3086538.
  7. ^ Harden CL (1 May 1994). "New antiepileptic drugs". Neurology. 44 (5): 787–95. doi:10.1212/WNL.44.5.787. PMID 8190276. S2CID 75925846.
  8. ^ "Archived copy" (PDF). Archived from the original (PDF) on 3 November 2013. Retrieved 28 January 2013.{{cite web}}: CS1 maint: archived copy as title (link)
  9. ^ Rogawski MA, Löscher W (July 2004). "The neurobiology of antiepileptic drugs". Nature Reviews Neuroscience. 5 (7): 553–64. doi:10.1038/nrn1430. PMID 15208697. S2CID 2201038. Archived from the original on 16 December 2020. Retrieved 20 September 2020.
  10. ^ Rogawski MA, Bazil CW (July 2008). "New molecular targets for antiepileptic drugs: alpha(2)delta, SV2A, and K(v)7/KCNQ/M potassium channels". Curr Neurol Neurosci Rep. 8 (4): 345–52. doi:10.1007/s11910-008-0053-7. PMC 2587091. PMID 18590620.
  11. ^ Meldrum BS, Rogawski MA (January 2007). "Molecular targets for antiepileptic drug development". Neurotherapeutics. 4 (1): 18–61. doi:10.1016/j.nurt.2006.11.010. PMC 1852436. PMID 17199015.
  12. ^ a b Kammerer M, Rassner, M. P., Freiman, T. M., Feuerstein, T. J. (2 May 2011). "Effects of antiepileptic drugs on GABA release from rat and human neocortical synaptosomes". Naunyn-Schmiedeberg's Archives of Pharmacology. 384 (1): 47–57. doi:10.1007/s00210-011-0636-8. PMID 21533993. S2CID 1388805.
  13. ^ Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, et al. (2013). Charpier S (ed.). "PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings". PLOS ONE. 8 (5): e64541. Bibcode:2013PLoSO...864541P. doi:10.1371/journal.pone.0064541. PMC 3664607. PMID 23724059.
  14. ^ Citraro R, et al. (2013). "Antiepileptic action of N-palmitoylethanolamine through CB1 and PPAR-α receptor activation in a genetic model of absence epilepsy". Neuropharmacology. 69: 115–26. doi:10.1016/j.neuropharm.2012.11.017. PMID 23206503. S2CID 27701532.
  15. ^ Porta, N., Vallée, L., Lecointe, C., Bouchaert, E., Staels, B., Bordet, R., Auvin, S. (2009). "Fenofibrate, a peroxisome proliferator-activated receptor-alpha agonist, exerts anticonvulsive properties". Epilepsia. 50 (4): 943–8. doi:10.1111/j.1528-1167.2008.01901.x. PMID 19054409. S2CID 6796135.
  16. ^ Lampen A, Carlberg C, Nau H (2001). "Peroxisome proliferator-activated receptor delta is a specific sensor for teratogenic valproic acid derivatives". Eur J Pharmacol. 431 (1): 25–33. doi:10.1016/S0014-2999(01)01423-6. PMID 11716839.
  17. ^ Maguire JH, Murthy AR, Hall IH (1985). "Hypolipidemic activity of antiepileptic 5-phenylhydantoins in mice". Eur J Pharmacol. 117 (1): 135–8. doi:10.1016/0014-2999(85)90483-2. PMID 4085542.
  18. ^ Hall IH, Patrick MA, Maguire JH (1990). "Hypolipidemic activity in rodents of phenobarbital and related derivatives". Archiv der Pharmazie. 323 (9): 579–86. doi:10.1002/ardp.19903230905. PMID 2288480. S2CID 46002731.
  19. ^ Frigerio F, Chaffard G, Berwaer M, Maechler P (2006). "The antiepileptic drug topiramate preserves metabolism-secretion coupling in insulin secreting cells chronically exposed to the fatty acid oleate". Biochem Pharmacol. 72 (8): 965–73. doi:10.1016/j.bcp.2006.07.013. PMID 16934763.
  20. ^ Kaminski RM, Rogawski MA, Klitgaard H (2014). "The potential of antiseizure drugs and agents that act on novel molecular targets as antiepileptogenic treatments". Neurotherapeutics. 11 (2): 385–400. doi:10.1007/s13311-014-0266-1. PMC 3996125. PMID 24671870.
  21. ^ Abou-Khalil BW (2007). "Comparative Monotherapy Trials and the Clinical Treatment of Epilepsy". Epilepsy Currents. 7 (5): 127–9. doi:10.1111/j.1535-7511.2007.00198.x. PMC 2043140. PMID 17998971.