Baklofen

Baclofen
(IUPAC) ime
	(RS)-4-amino-3-(4-hlorofenil)butanoinska kiselina
Klinički podaci
Robne marke	Liorezal, Liofen
AHFS/Drugs.com	Monografija
Identifikatori
CAS broj	1134-47-0
ATC kod	M03BX01
PubChem	2284
DrugBank	DB00181
ChemSpider	2197
UNII	H789N3FKE8
KEGG	D00241
ChEBI	CHEBI:2972
ChEMBL	CHEMBL701
Hemijski podaci
Formula	C10H12ClNO2
Mol. masa	213,661 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C10H12ClNO2/c11-9-3-1-7(2-4-9)8(6-12)5-10(13)14/h1-4,8H,5-6,12H2,(H,13,14) ; Key: KPYSYYIEGFHWSV-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	dobro se apsorbuje
Vezivanje za proteine plazme	30%
Metabolizam	85% se izlučuje nepromenjeno urinom/fekalijama. 15% se metabolizuje deaminacijom
Poluvreme eliminacije	1.5 do 4 sata
Izlučivanje	renalno (70-80%)
Farmakoinformacioni podaci
Licenca	US FDA:link
Trudnoća	C(US)
Pravni status	℞-only (SAD)
Način primene	Oralno, intratekalno

Baklofen (Kemstro, Lioresal, Liofen, Gablofen, i Beklo) je derivat gama-aminobuterne kiseline (GABA). On se prvenstveno koristi za tretiranje spasticiteta. On je u ranom stadijumu istraživanja za moguću upotrebu u tretmanu alkoholizma.

Baklofen je agonist GABA_B receptora.^[6]^[7] Njegovo korisno dejstvo na spasticitet je rezult uticaja na kičmene i supraspinalne lokacije. Baklofen se takođe može koristiti za tretiranje štucanja. Pokazano je da prečava porast telesne temperature indukovane lekom MDMA kod pacova.^[8]

Istraživanja su pokazala da je baklofen efektivan u tretmanu alkoholne zavisnosti i povlačenja, putem inhibicije simptoma povlačenja i žudnje.^[9]

Korisno svojstvo bajlofena je da se tolerancija ne javlja u znatnoj meri — baklofen zadržava svoje terapeutske antispazmodičke efekte čak i nakon nekoliko godina stalne upotrebe.^[10] Međutim, tolerancija se može razviti kod nekih pacijenata koji primaju lek intratekalo.^[11]^[12]^[13]

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Mezler M., Müller T., Raming K. (February 2001). „Cloning and functional expression of GABA(B) receptors from Drosophila”. Eur. J. Neurosci. 13 (3): 477–486. DOI:10.1046/j.1460-9568.2001.01410.x. PMID 11168554.
↑ Dzitoyeva S., Dimitrijevic N., Manev H. (April 2003). „Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence”. Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5485–5490. Bibcode 2003PNAS..100.5485D. DOI:10.1073/pnas.0830111100. PMC 154371. PMID 12692303.
↑ Bexis S., Phillis B. D., Ong J., White J. M., Irvine R. J. (2004-04-09). „Baclofen prevents MDMA-induced rise in core body temperature in rats”. Drug and Alcohol Dependence 74 (1): 89–96. DOI:10.1016/j.drugalcdep.2003.12.004. PMID 15072812.
↑ Addolorato, G.; Leggio, L.; Ferrulli, A.; Cardone, S.; Vonghia, L.; Mirijello, A.; Abenavoli, L.; D'Angelo, C. i dr.. (Dec 2007). „Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study”. Lancet 370 (9603): 1915–1922. DOI:10.1016/S0140-6736(07)61814-5. PMID 18068515.
↑ Gaillard J. M. (May 1977). „Comparison of two muscle relaxant drugs on human sleep: diazepam and parachlorophenylgaba”. Acta Psychiatr Belg 77 (3): 410–425. PMID 200069.
↑ Heetla, H. W.; Staal, M. J.; Kliphuis, C.; Van Laar, T. (2009). „The incidence and management of tolerance in intrathecal baclofen therapy”. Spinal Cord 47 (10): 751–756. DOI:10.1038/sc.2009.34. PMID 19333246.
↑ Nielsen, J. F.; Hansen, H. J.; Sunde, N.; Christensen, J. J. (2002). „Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen”. Clinical neurology and neurosurgery 104 (2): 142–145. PMID 11932045.
↑ Heetla, H. W.; Staal, M. J.; Van Laar, T. (2009). „Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion”. Spinal Cord 48 (6): 483–486. DOI:10.1038/sc.2009.156. PMID 19918253.

Spoljašnje veze

	Portal Medicina
	Portal Hemija

Intrathecal Baclofen Therapy Arhivirano 2012-02-04 na Wayback Machine-u Cleveland Clinic Information Center. 15 June 2001.
FYI: Baclofen (Lioresal) Arhivirano 2012-12-28 na Wayback Machine-u, from the New York State Office of Alcoholism and Substance Abuse Services
Intrathecal Baclofen Arhivirano 2013-05-21 na Wayback Machine-u, from Nottingham University Hospitals NHS Trust, Queen's Medical Centre
U.S. National Library of Medicine: Drug Information Portal - Baclofen

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Joanne Wixon, Douglas Kell (2000). „Website Review: The Kyoto Encyclopedia of Genes and Genomes — KEGG”. Yeast 17 (1): 48–55. DOI:10.1002/(SICI)1097-0061(200004)17:1<48::AID-YEA2>3.0.CO;2-H.

[5] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[pmid11168554-6] Mezler M., Müller T., Raming K. (February 2001). „Cloning and functional expression of GABA(B) receptors from Drosophila”. Eur. J. Neurosci. 13 (3): 477–486. DOI:10.1046/j.1460-9568.2001.01410.x. PMID 11168554.

[pmid12692303-7] Dzitoyeva S., Dimitrijevic N., Manev H. (April 2003). „Gamma-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence”. Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5485–5490. Bibcode 2003PNAS..100.5485D. DOI:10.1073/pnas.0830111100. PMC 154371. PMID 12692303.

[8] Bexis S., Phillis B. D., Ong J., White J. M., Irvine R. J. (2004-04-09). „Baclofen prevents MDMA-induced rise in core body temperature in rats”. Drug and Alcohol Dependence 74 (1): 89–96. DOI:10.1016/j.drugalcdep.2003.12.004. PMID 15072812.

[pmid18068515-9] Addolorato, G.; Leggio, L.; Ferrulli, A.; Cardone, S.; Vonghia, L.; Mirijello, A.; Abenavoli, L.; D'Angelo, C. i dr.. (Dec 2007). „Effectiveness and safety of baclofen for maintenance of alcohol abstinence in alcohol-dependent patients with liver cirrhosis: randomised, double-blind controlled study”. Lancet 370 (9603): 1915–1922. DOI:10.1016/S0140-6736(07)61814-5. PMID 18068515.

[10] Gaillard J. M. (May 1977). „Comparison of two muscle relaxant drugs on human sleep: diazepam and parachlorophenylgaba”. Acta Psychiatr Belg 77 (3): 410–425. PMID 200069.

[11] Heetla, H. W.; Staal, M. J.; Kliphuis, C.; Van Laar, T. (2009). „The incidence and management of tolerance in intrathecal baclofen therapy”. Spinal Cord 47 (10): 751–756. DOI:10.1038/sc.2009.34. PMID 19333246.

[12] Nielsen, J. F.; Hansen, H. J.; Sunde, N.; Christensen, J. J. (2002). „Evidence of tolerance to baclofen in treatment of severe spasticity with intrathecal baclofen”. Clinical neurology and neurosurgery 104 (2): 142–145. PMID 11932045.

[13] Heetla, H. W.; Staal, M. J.; Van Laar, T. (2009). „Tolerance to continuous intrathecal baclofen infusion can be reversed by pulsatile bolus infusion”. Spinal Cord 48 (6): 483–486. DOI:10.1038/sc.2009.156. PMID 19918253.

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