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Baclofen: Therapeutic and Toxic Mechanisms of Action (Review)

https://doi.org/10.15360/1813-9779-2020-4-60-71

Abstract

Baclofen is a muscle relaxant, which is a beta-p-chlorophenyl derivative of an inhibitory neurotransmitter GABA. This drug may have serious side effects and cause life-threatening conditions which may recellular receptors to clarify the pathogenesis of life-threatening conditions caused by poisoning with this drug.
The search was done using the PubMed and Scopus databases, and the final selection of 82 sources was made based on the relevance to the topic of this review and the type of article. The review included both the results of randomized studies and individual reports.
The review briefly discusses the history of baclofen synthesis and its application in clinical practice, indications for prescription, mechanism of action and the specific features of its metabolism, its effect on the CNS, signs and symptoms of withdrawal syndrome, overdose and acute poisoning, as well as the interaction of baclofen with other drugs.
C
onclusion. Multiple studies failed to make definite conclusions about mechanisms of baclofen toxicity. To completely reveal the pathogenesis of life-threatening conditions occurring due to baclofen use, further studies of molecular and cellular effects of this drug, as well as genetic factors controlling its metabolism, are warranted.

About the Authors

О. L. Romanova
V. A. Negovsky Scientific Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology; Peoples’ Friendship University of Russia
Russian Federation

Оlga L. Romanova

25 Petrovka Str., Build. 2, 107031 Moscow; 

6 Miklukho-Maсlaya Str., 117198 Moscow



M. L. Blagonravov
Peoples’ Friendship University of Russia
Russian Federation
6 Miklukho-Maсlaya Str., 117198 Moscow


M. A. Kislov
I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russia
Russian Federation
8 Trubetskaya Str., Bldg. 2, 119991 Moscow


References

1. Romanova O.L., Sudukov D.V., Golubev M.A., Blagonravov M.L., Goshkoev V.V., Churilov A.A. Pathologic Changes in the Liver During Acute Exposure to Clozapine and Its Combination with Ethanol (Experimental Study). General Reanimatology=Obshchaya Reanimatologiya. 2019; 15 (2): 27–35. [In Russ.] DOI: 10.15360/1813-9779-2019-2-27-35

2. Livanov G.A., Lodyagin A.N., Razina A.А., Glushkov S.I., Ivanova A.A., Volchkova E.V., Batotsyrenov B.V. Favorable Outcome of Severe Acute Methadone Poisoning (Clinical Case). General Reanimatology=Obshchaya Reanimatologiya. 2018; 14 (5): 25–31. [In Russ.]. DOI: 10.15360/1813-9779-2018-5-25-31

3. Kuznetsov B. V., Lodyagin A. N., Batotsyrenov B. V., Nezhentseva I. V., Baranov D. V. Features of clinical manifestation of acute methadone poisoning complicated by development of positional compression syndrome and systemic rhabdomyolysis. Toksikolog. vestnik. 2015; 4: 38–43. [In Russ.]

4. Livanov G.A., Loladze A.T., Batotsyrenov B.V., Lodyagin A.N., Glushkov S.I., Kharitonova T.V., Ivanova A.A., Baranov D.V., Antonova A.M. Acute Poisoning with Methadone (Dolphin) (Review). General Reanimatology=Obshchaya Reanimatologiya. 2017; 13 (3): 48–63. [In Russ.]. DOI: 10.15360/1813-9779-2017-3-48-63

5. Romanova O.L., Sundukov D.V., Golubev A.M., Blagonravov M.L. Morphological Changes Depending on the Contentof Clozapine and its Metabolites in the Lungs and Serum (Experimental Study). General Reanimatology=Obshchaya Reanimatologiya. 2018; 14 (4): 44–51. [In Russ.]. DOI: 10.15360/1813-9779-2018-4-44-51

6. Hendry-Hofer T., Ng P., Witeof A., Mahon S., M.Brenner, Boss G., V. Bebarta A Review on Ingested Cyanide: Risks, Clinical Presentation, Di agnostics, and Treatment Challenges. J Med Toxicol, 15 (2): 128–133 PMID: 30539383. PMCID: PMC6441064 (available on 2020-04-01) DOI: 10.1007/s13181-018-0688-y

7. Anseeuw K., Delvau N., Burillo-Putze G., De Iaco F., Geldner G., Holmström P., Lambert Y; Sabbe M. Cyanide poisoning by fire smoke inhalation: a European expert consensus. European Journal of Emergency Medicine. 2013; 20 (1): 2–9. DOI: 10.1097/mej.0b013e328357170b. PMID 22828651.

8. Baclofen Monograph for Professionals. Drugs.com. American Society of Health-System Pharmacists. Retrieved 3 March 2019.

9. Product Information Clofen. TGA eBusiness Services. Millers Point, Australia: Alphapharm Pty Limited. 7 June 2017. Retrieved 15 August 2017

10. Mashkovsky M. D. Medicinal products. 17th ed. M.: Novaya volna; 2019: 73–74. [In Russ.].

11. Issa S.Y., Hafez E.M., El-Banna A.S.,Abdel Rahman S.M., AlMazroua M.K., El-Hamd M.A. Baclofen Systemic Toxicity: Experimental Histopathological and Biochemical Study. Hum Exp Toxicol. 2018; 37 (4): 431-441 PMID: 28565970. DOI: 10.1177/0960327117712369

12. Reynolds K., Kaufman R., Korenoski A., Fennimore L., Shulman J., Lynch M. Trends in gabapentin and baclofen exposures reported to U.S. poison centers. Clinical Toxicology. 2019; 1–10. DOI: 10.1080/15563650.2019.1687902. ISSN 1556-3650. PMID 31786961.

13. Charifou Y., Martinet O., Jabot J., Gauzere B.A., Allyn J., Vandroux D. Baclofen Intoxication Cases in an Intensive Care Unit. Anaesth Crit Care Pain Med, 2016; 35 (2): 169–170. PMID: 26667597. DOI: 10.1016/j.accpm.2015.10.003

14. Dukova O.A., Pokrovskij A.A., Melent'ev A. B., Krasnov E.A., Suvorova E.V., Efremov A. A. Lethal intoxication with baclofen. Sudebno-med-itsinskaya ekspertiza. 2015; 58 (1): 35–39. [In Russ.]. DOI: 10.17116/sudmed201558135-39

15. Moffat A.C., Osselton M.D.,Widdop B. (eds.) Clarke’s analysis of drugs and poisons. London: Pharmac Press 2011.

16. Kapil V., Green J.L., Le Lait M., Dargan P.I. Misuse of the c-aminobutyric acid analogues baclofen, gabapentin and pregabalin in the UK.Br J Clin Pharmacol. 2014; 78 (1): 190–191. PMID: 25083536. PMCID: PMC4168395. DOI: 10.1111/bcp.12277

17. Slavova S., Miller A., Bunn T.L.,White J.R., Kirschke D., Light T., Christy D., Thompson G. Winecker R. Prevalence of gabapentin in drug overdose postmortem toxicology testing results. Drug Alcohol Depend. 2018 May 1; 186: 80–85. PMID: 29554591. DOI: 10.1016/j.drugalcdep.2018.01.018

18. Beraha, E., Bodewits,P., van den Brink,W., Wiers, R. Speaking fluently with baclofen? BMJ Case Reports. 2017. bcr-2016. DOI: 10.1136/bcr2016-218714.

19. Smith R.V., Lofwall M.R., Havens J.R. Abuse and diversion of gabapentin among nonmedical prescription opioid users in Appalachian Kentucky. Am J Psychiatry. 2015; 172 (5): 487–488. DOI: 10.1176/appi.ajp.2014.14101272.

20. Brayfield A, ed. (9 January 2017). Baclofen: Martindale: The Complete Drug Reference. MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 15 August 2017

21. Smith R., Havens J., Walsh S. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016; 111 (7): 1160–1174. DOI: 10.1111/add.13324

22. de Marcellus C.., le Bot S., Decleves X., Baud F., Renolleau S., Oualha M. Report of severe accidental baclofen intoxication in a healthy 4year-old boy and review of the literature. Arch Pediatr. 2019; 26 (8): 475–478. DOI: 10.1016/j.arcped.2019.10.003.

23. Weißhaar G.F., Hoemberg M., Bender K., Bangen U., Herkenrath P., Eifinger F., Rothschild M., Roth B., Oberthuer A. Baclofen intoxication: a «fun drug» causing deep coma and nonconvulsive status epilepticus--a case report and review of the literature. Eur J Pediatr. 2012; 171 (10): 1541–1547. PMID: 22729246. DOI: 10.1007/s00431-012-1780-y

24. Tagirov A.A., Larionov S.S. Acute intentional poisoning with the drug «Baclofen» in adolescents. Uspekhi sovremennogo estestvoz-naniya.2014; 6: 94–94. [In Russ.].

25. Agabio R., Preti A., Gessa G.L. Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review. European Addiction Research. 2013; 19 (6): 325–345. DOI: 10.1159/000347055. ISSN 14219891. PMID 23775042.

26. Thill C., Di Constanzo L., Pessey F., Aries P., Montelescaut É., Sapin J., Vaillant C., Drouillard I. Usefulness of Plasma Drug Monitoring in Severe Baclofen Poisoning. Clin Toxicol (Phila). 2015; 53 (9): 923–924. PMID: 26415080. DOI: 10.3109/15563650.2015.1088158

27. Gablofen (Baclofen) FDA Full Prescribing Information. US Food and Drug Administration. Retrieved 2016-01-2

28. Rolland B., Paille F., Gillet C., Rigaud A., Moirand R., Dano C., Dematteis M., Mann K., Aubin H.J. Pharmacotherapy for alcohol dependence: the 2015 recommendations of the French Alcohol Society, issued in partnership with the European Federation of Addiction Societies. CNS Neurosci Ther. 2016; 22: 25–37. PMID: 26768685. PMCID: PMC6492872. DOI: 10.1111/cns.12489

29. Reynaud M., Aubin H-J., Trinquet F., Zakine B., Dano C., Dematteis M., Trojak B., Paille F., Detilleux M.. A randomized, placebo-controlled study of high-dose baclofen in alcohol-dependent patients—the ALPADIR study. Alcohol Alcohol. 2017; 52: 439–446. PMID: 28525555. DOI: 10.1093/alcalc/agx030

30. Müller C.A., Geisel O., Pelz P., Higl V., Krüger J., Stickel A., Beck A., Wernecke K.D., Hellweg R., Heinz A. High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial. Eur Neuropsychopharmacol. 2015; 25: 1167–1177. PMID: 26048580. DOI: 10.1016/j.euroneuro.2015.04.002

31. Rigal L., Legay Hoang L., Alexandre-Dubroeucq C., Pinot J., Le Jeunne C., Jaury P. Tolerability of high-dose baclofen in the treatment of patients with alcohol disorders: a retrospective study. Alcohol Alcohol. 2015; 50: 551–557. DOI: 10.1093/alcalc/agv052

32. Léger M., Brunet M., Le Roux G., Lerolle N., Boels D. Baclofen self-poisoning in the era of changing indication: multicentric reports to a French poison control centre. Alcohol Alcohol. 2017; 52: 665–670. DOI: 10.1093/alcalc/agx072

33. Franchitto N., De Haro L., Pélissier F. Focusing solely on the effect of the medication without taking a holistic view of the patient does not seem very constructive. Clin Toxicol. 2018; 56: 309. DOI: 10.1080/15563650.2017.1373781

34. Beck A., Pelz P., Lorenz R.C., Charlet K., Geisel O., Heinz A.,Wüstenberg T., Müller C.A. Effects of High-Dose Baclofen on Cue Reactivity in Alcohol Dependence: A Randomized, Placebo-Controlled pharmacofMRI Study. Eur Neuropsychopharmacol. 2018; 28 (11): 1206–1216 PMID: 30217552. DOI: 10.1016/j.euroneuro.2018.08.507

35. Vourc'h M., Feuillet F., Mahe P.-J., Sebille V., Asehnoune K., BACLOREA trial group. Baclofen to Prevent Agitation in Alcohol-Addicted Patients in the ICU: Study Protocol for a Randomised Controlled Trial. Trials. 2016; 17 (1): 415. PMID: 27542731. PMCID: PMC4992221. DOI: 10.1186/s13063-016-1539-2

36. Dixit D., Endicott J., Burry L., Ramos L., Yeung S.Y.A., Devabhakthuni S., Chan C.,Tobia A., Bulloch M.N. Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients. Pharmacotherapy. 2016; 36 (7): 797–822. PMID: 27196747. DOI: 10.1002/phar.1770

37. Beraha E.M., Salemink E., Goudriaan A.E., Bakker A., de Jong D., Smits N., Zwart J.W., Geest D.V., Bodewits P., Schiphof T., Defourny H., van Tricht M., van den Brink W., Wiers R.W. Efficacy and safety of highdose baclofen for the treatment of alcohol dependence: A multicentre, randomised, double-blind controlled trial. European Neuropsychopharmacology.2016; 26 (12): 1950–1959. DOI: 10.1016/j.euroneuro.2016.10.006. PMID 27842939.

38. Minozzi S., Saulle R., Rösner S. Baclofen for alcohol use disorder. Cochrane Database Syst Rev. 2018; 26 (11): CD012557. PMID: 30484285. PMCID: PMC6517285. DOI: 10.1002/14651858.CD012557.pub2

39. Girish K., Vikram Reddy K., Pandit L.V., Pundarikaksha H.P., Vijendra R., Vasundara K., Manjunatha R., Nagraj M., Shruthi R. A randomized, open-label, standard controlled, parallel group study of efficacy and safety of baclofen, and chlordiazepoxide in uncomplicated alcohol withdrawal syndrome. Biomed J. 2016; 39 (1): 72–80. DOI: 10.1016/j.bj.2015.09.002. PMID: 27105601. PMCID: PMC6138810

40. Simon N., Franchitto N., Rolland B. Pharmacokinetic Studies of Baclofen Are Not Sufficient to Establish an Optimized Dosage for Management of Alcohol Disorder. Front Psychiatry. 2018; 9: 485. PMID: 30349489. PMCID: PMC6186984. DOI: 10.3389/fpsyt.2018.00485

41. Schiess M.C., Eldabe S., Konrad P., Molus L., Spencer R., Stromberg K., Weaver T., Punkett R. Intrathecal Baclofen for Severe Spasticity: Longitudinal Data From the Product Surveillance Registry. Neuromodulation. 2020. DOI: 10.1111/ner.13097. [Epub ahead of print] PMID: 31989725

42. van den Brink W. Baclofen: A Game Changer in the Treatment of Alcohol Dependence. Alcohol Alcohol. 2020; 55 (1): 46–47. DOI: 10.1093/alcalc/agz085. PMID: 32031207

43. Krupickij E.M., Rybakova K.V., Kiselev A.S., Alekseeva Yu.V., Berncev V.A., Chekhlatyj E.I., Zubova E.Yu., Popov Yu.V., Neznanov N.G. Efficacy and safety of baclofen in the treatment of alcohol dependence (double-blind randomized placebo-controlled pilot study). Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2015; 115 (6): 53–62. [In Russ.]. DOI: 10.17116/jnevro20151156153-62

44. McLaughlin M.J., He Y., Brunstrom-Hernandez J., Thio L.L., Carleton B.C., Ross C.J.D., Gaedigk A., Lewandowski A., Dai H., Jusko W.J., Leeder J.S. Response in Children With Cerebral Palsy. PM R. 2018; 10 (3): 235–243. DOI: 10.1016/j.pmrj.2017.08.441.

45. Navarrete-Opazo A.A., Gonzalez W., Nahuelhual P. Effectiveness of Oral Baclofen in the Treatment of Spasticity in Children and Adolescents With Cerebral Palsy. Arch Phys Med Rehabil 2016; 97 (4): 604–618. DOI: 10.1016/j.apmr.2015.08.417. PMID: 26321489

46. Furr-Stimming E., Boyle A.M., Schiess M.C. Spasticity and Intrathecal Baclofen. Semin Neurol 2014; 34: 591–596. PMID: 5520030. DOI: 10.1055/s-0034-1396012

47. Haney M., Hart C.L., Vosburg S.K., Comer S.D., Reed S.C., Cooper Z.D., Foltin R.W. Effects of baclofen and mirtazapine on a laboratory model of marijuana withdrawal and relapse. Psychopharmacology (Berl). 2010; 211 (2): 233–244. DOI: 10.1007/s00213-010-1888-6.

48. Kampman, K.M.. New medications for the treatment of cocaine dependence. Psychiatry (Edgmont), 2005; 2 (12): 44–48. PMC 2994240. PMID 21120115.

49. Froestl W. GABA Receptor Pharmacology — A Tribute to Norman Bowery. Advances in Pharmacology. 2010: 58: 19–62. ISBN 978-0-12378647-0. DOI: 10.1016/S1054-3589(10)58002-5.

50. Yogeeswari P., Ragavendran J.V., Sriram D. An update on GABA analogs for CNS drug discovery. Recent patents on CNS drug discovery. 2006; 1 (1): 113–118. PMID 18221197. DOI: 10.2174/157488906775245291.

51. Mezler M., Müller T., Raming K. Cloning and functional expression of GABA (B) receptors from Drosophila. Eur. J. Neurosci. 2001; 13 (3): 477–486. PMID 11168554. DOI: 10.1046/j.1460-9568.2001.01410.x.

52. Carter L.P., Koek W., France C.P. Behavioral analyses of GHB: Receptor mechanisms. Pharmacol. Ther., 2008; 121 (1): 100–114. DOI: 10.1016/j.pharmthera.2008.10.003.

53. Reis G.M., Duarte I.D. Baclofen, an agonist at peripheral GABAB receptors, induces antinociception via activation of TEA-sensitive potassium channels. Br J Pharmacol. 2006; 149 (6): 733–739. DOI: 10.1038/sj.bjp.0706898

54. Zvejniece L.,Vavers E., Svalbe B.,Veinberg G., Rizhanova K., Liepins V., Kalvinsh I., Dambrova M. R-phenibut binds to the α2-δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects. Pharmacol. Biochem. Behav. 2015; 137: 23–29. DOI: 10.1016/j.pbb.2015.07.014. PMID 26234470.

55. Potes C.S., Neto F.L., Castro-Lopes J.M. Administration of baclofen, a gamma-aminobutyric acid type B agonist in the thalamic ventrobasal complex, attenuates allodynia in monoarthritic rats subjected to the ankle-bend test. J Neurosci Res. 2006; 83 (3): 515–523. PMID: 16400658. DOI: 10.1002/jnr.20737

56. van Nieuwenhuijzen, P.S.; McGregor, I.S.; Hunt, G.E. The distribution of γ-hydroxybutyrate-induced Fos expression in rat brain: Comparison with baclofen. Neuroscience.2009; 158 (2): 441–455. DOI: 10.1016/j.neuroscience.2008.10.011. ISSN 0306-4522. PMID 18996447.

57. Kumru H., Albu S., Kofler M., Vidal J. The long-term analgesic effect of intrathecal baclofen on neuropathic pain in patients with spinal cord injury. Neurologia. 2020 Jan 14. pii: S0213–4853 (19)30135-5 PMID: 31952888. DOI: 10.1016/j.nrl.2019.09.009

58. Heetla H.W., Proost J.H., Molmans B.H., Staal M.J., van Laar T. A pharmacokinetic–pharmacodynamic model for intrathecal baclofen in patients with severe spasticity. British Journal of Clinical Pharmacology. 2016; 81 (1): 101–112. PMID: 27099877. PMCID: PMC4693571. DOI: 10.1111/bcp.12781

59. Dias L.S., Vivek G., Manthappa M., Acharya R.V. Role of hemodialysis in baclofen overdose with normal renal function. Indian J Pharmacol. 2011; 43: 722–723. PMID: 22144783. PMCID: PMC3229794. DOI: 10.4103/0253-7613.89835.

60. Bowman A., Ayyangar R., Gonzales I., Hornyak J. Intrathecal baclofen toxicity in a patient with acute kidney injury. J Pediatr Rehabil Med. 2019; 12 (3): 313–315. PMID: 31476182. DOI: 10.3233/PRM-180598

61. Sanchez-Ponce R., Wang L.Q., Lu W., von Hehn J., Cherubini M., Rush R. Metabolic and Pharmacokinetic Differentiation of STX209 and Racemic Baclofen in Humans. Metabolites. 2012; 2 (3): 596–613. PMID: 24957649. PMCID: PMC3901214. DOI: 10.3390/metabo2030596.

62. Muanda F.T.,Weir M.A., Bathini L., Blake P.G., Chauvin K., Dixon S.N., McArthur E., Sontrop J.M., Moist.L., Garg A.X. Association of Baclofen With Encephalopathy in Patients With Chronic Kidney Disease. JAMA. 2019 Nov 9. PMID: 31705755. PMCID: PMC6865230. DOI: 10.1001/jama.2019.17725

63. Chartier M., Tannous S., Benturquia N., Labat L., Reis R., Risède P., Chevillard L., Mégarbane B. Baclofen-Induced Neuro-Respiratory Toxicity in the Rat: Contribution of Tolerance and Characterization of Withdrawal Syndrome Toxicological Sciences. 2018; 164 (1): 153–165. PMID: 29945230. DOI: 10.1093/toxsci/kfy073

64. Chartier M., Malissin I., Tannous S., Labat L., Risède P., Mégarbane B., Chevillard L. Baclofen-induced encephalopathy in overdose — Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018; 86 (30): 131–139. PMID: 29782961. DOI: 10.1016/j.pnpbp.2018.05.016

65. Mikhaylov A.Y., Berezina I.Y., Potskhveriya M.M., Sumsky L.I. Electroencephalography showing dying brain in a patient with acute baclofen poisoning. Russian Sklifosovsky Journal «Emergency Medical Care»=Neotlozhnaya medicinskaya pomoshch'. Zhurnal im. N.V. Sklifosovskogo. 2017; 6 (4): 371–375. [In Russ.]. DOI: 10.23934/2223-9022-2017-6-4-371-375

66. Ostermann M.E.,Young B., Sibbald W.J., Nicole M.W. Coma mimicking brain death following baclofen overdose. Intensive Care Med. 2000; 26: 1144–1146. PMID: 11030173. DOI: 10.1007/s001340051330

67. Salazar M.L., Eiland L.S. Intrathecal baclofen withdrawal resembling serotonin syndrome in an adolescent boy with cerebral palsy. Pediatr Emerg Care. 2008; 24 (10): 691–693. PMID: 19240673. DOI: 10.1097/PEC.0b013e318188a952

68. Mohammed I., Hussain A. Intrathecal baclofen withdrawal syndromea life-threatening complication of baclofen pump: a case report. BMC Clin Pharmacol. 2004; 4: 6. PMID: 15301690. PMCID: PMC514562. DOI: 10.1186/1472-6904-4-6

69. Hansen C.R., Gooch J.L., Such-Neibar T. Prolonged, severe intrathecal baclofen withdrawal syndrome: a case report. Arch Phys Med Rehabil. 2007; 88 (11): 1468–1471. PMID: 17964889. DOI: 10.1016/j.apmr.2007.07.021

70. Motta F., Antonello C.E. Analysis of complications in 430 consecutive pediatric patients treated with intrathecal baclofen therapy: 14-year experience. J Neurosurg Pediatr. 2014 Mar; 13 (3): 301–306. DOI: 10.3171/2013.11.PEDS13253.

71. Defayette A., Perrello A., Brewer T., Picano J., Ahmed S. Enteral baclofen withdrawal managed with intravenous dexmedetomidine: A case report. Am J Health Syst Pharm. 2020 Jan 13. pii: zxz332. PMID: 31930325. DOI: 10.1093/ajhp/zxz332

72. Richter E.K., Baldovini A., Gandía Blasco V.M., Leone M., Albanèse J. About baclofen withdrawal syndrome. Presse Med. 2016; 45 (5): 547–548. PMID: 27016853. DOI: 10.1016/j.lpm.2016.02.012

73. Alden T.D., Lytle R.A., Park T.S., Noetzel M.J., Ojemann J.G. Intrathecal baclofen withdrawal: a case report and review of the literature. Childs Nerv Syst. 2002; 18 (9–10): 522–525. Epub 2002 Jul 23. PMID: 12382179. DOI: 10.1007/s00381-002-0634-8

74. Shirley K.W., Kothare S., Piatt J.H Jr, Adirim T.A. Intrathecal baclofen overdose and withdrawal. Pediatr Emerg Care. 2006; 22 (4): 258–261. PMID: 16651918. DOI: 10.1097/01.pec.0000210175.40763.c5

75. Roberge R.J., Martin T.G., Hodgman M., Benitez J.G., Brunswick J.E. Supraventricular tachyarrhythmia associated with baclofen overdose. ClinToxil 1994; 32: 291–297. PMID: 8007036. DOI: 10.3109/15563659409017961

76. Katyal R., Samkutty D., Muzammil S.M., Saucedo S. Baclofen toxicity presenting as myoclonic status epilepticus. Neurol Clin Pract. 2019 Dec; 9 (6): 516–518. DOI: 10.1212/CPJ.0000000000000686. PMID: 32042496

77. Rolland B., Deheul S., Danel T., Bordet R., Cottencin O. A case of de novo seizures following a probable interaction of high-dose baclofen with alcohol. Alcohol Alcohol. 2012; 47 (5): 577–580. PMID: 22753796. DOI: 10.1093/alcalc/ags076

78. de Witte L.D., Dekker D., Veraart J., Kromkamp M., Kaasjager K. Aggression and Restlessness Following Baclofen Overdose: The Narrow Line Between Intoxication and Withdrawal Symptoms. Ned Tijdschr Geneeskd. 2016; 160: A9604 [Article in Dutch] PMID: 27484417

79. Wolf M.E, Mosnaim A.D. Baclofen-induced manic symptoms: case report and systematic review. Psychosomatics. 2017; 58: 94. DOI: 10.1016/j.psym.2016.08.004

80. Hsieh M.J., Chen S.C., Weng T.I., Fang C.C., Tsai T.J. Treating baclofen overdose by hemodialysis. Am J Emerg Med 2012; 30: 1654. PMID: 22030181. DOI: 10.1016/j.ajem.2011.07.013

81. Czuczwar M., Kiś J., Swiader M., Turski W.A., Przesmycki K. Evaluation of interaction between valproate and baclofen in the formalin test in mice. Pol J Pharmacol. 2001; 53 (1): 51–54. PMID: 11785912

82. Chern T.L., Kwan A. Flumazenil-induced seizure accompanying benzodiazepine and baclofen intoxication. Am J Emerg Med 1996; 14: 231–232. PMID: 8924153. DOI: 10.1016/S0735-6757(9Alk6)90140-0


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Romanova О.L., Blagonravov M.L., Kislov M.A. Baclofen: Therapeutic and Toxic Mechanisms of Action (Review). General Reanimatology. 2020;16(4):60-71. https://doi.org/10.15360/1813-9779-2020-4-60-71

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