Rotigotin

Rotigotin transdermalni flaster
(IUPAC) ime
	(S)-6-[propil(2-tiofen-2-iletil)amino]-5,6,7,8- tetrahidronaftalen-1-ol
Klinički podaci
AHFS/Drugs.com	Mikromedeks, detaljne potrošačke informacije
MedlinePlus	a607059
Identifikatori
CAS broj	92206-54-7
ATC kod	N04BC09
PubChem	57537
DrugBank	DB05271
ChemSpider	51867
UNII	87T4T8BO2E
ChEMBL	CHEMBL1303
Hemijski podaci
Formula	C19H25NOS
Mol. masa	315,474 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3 ; Key: KFQYTPMOWPVWEJ-UHFFFAOYSA-N
Farmakokinetički podaci
Bioraspoloživost	37% (transdermalno)
Vezivanje za proteine plazme	92%
Metabolizam	Hepatički (CYP-posredovano)
Poluvreme eliminacije	5–7 sati
Izlučivanje	Urin (71%), Fekalije (23%)
Farmakoinformacioni podaci
Trudnoća	?
Pravni status	℞ Prescription only
Način primene	Transdermalni flaster

Rotigotin (Neupro) je neergolinski dopaminski agonist koji se koristi za lečenje Parkinsonove bolesti i sindroma nemirnih nogu (RLS) u Evropi i SAD-u.^[5]^[6] On se formuliše kao jednodnevni transdermalni flaster koji omogućava spor i konstantan unos leka tokom 24 časovnog perioda.^[5]^[5]

Poput drugih dopaminskih agonista, za rotigotin je pokazano da poseduje antidepresivne efekte i da može da bude koristan u lečenju depresije.^[7]

Hemija

Rotigotin je analogan sa 7-OH-DPAT i UH-232. Sva tri jedinjenja su derivati aminotetralina. Ova jedinjenja imaju sličnu strukturu sa dopaminom, što uslovljava njihovu farmakologiju.

Jedan od mogućih sintetičkih puteva je:^[8]

Farmakologija

Rotigotin poseduje slediće in vitro profile vezivanja za receptore:^[9]

D₁ receptor (K_i = 83 nM)
D₂ receptor (K_i = 13.5 nM)
D₃ receptor (K_i = 0.71 nM)
D_4.2 receptor (K_i = 3.9 nM)
D_4.4 receptor (K_i = 15 nM)
D_4.7 receptor (K_i = 5.9 nM)
D₅ receptor (K_i = 5.4 nM)
α_1A-adrenergički receptor (K_i = 176 nM)
α_1B-adrenergički receptor (K_i = 273 nM)
α_2A-adrenergički receptor (K_i = 338 nM)
α_2B-adrenergički receptor (K_i = 27 nM)
α_2C-adrenergički receptor (K_i = 135 nM)
5-HT_1A receptor (K_i = 30 nM)
5-HT₇ receptor (K_i = 86 nM)
H₁ receptor (K_i = 330 nM)

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
↑ 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
↑ ^5,0 ^5,1 ^5,2 Chen JJ, Swope DM, Dashtipour K, Lyons KE (December 2009). „Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease”. Pharmacotherapy 29 (12): 1452–67. DOI:10.1592/phco.29.12.1452. PMID 19947805.
↑ Davies S (September 2009). „Rotigotine for restless legs syndrome”. Drugs of Today (Barcelona, Spain : 1998) 45 (9): 663–8. DOI:10.1358/dot.2009.45.9.1399952. PMID 19956807.
↑ Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). „Antidepressant properties of rotigotine in experimental models of depression”. European Journal of Pharmacology 548 (1-3): 106–14. DOI:10.1016/j.ejphar.2006.07.022. PMID 16959244.
↑ Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.
↑ Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H (January 2009). „The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease”. Naunyn-Schmiedeberg's Archives of Pharmacology 379 (1): 73–86. DOI:10.1007/s00210-008-0341-4. PMID 18704368.

Povezano

Spoljašnje veze

	Portal Medicina
	Portal Hemija

Rotigotin (SPM-962) Arhivirano 2011-09-03 na Wayback Machine-u

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[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] 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

[pmid19947805-5] 5,0 ^5,1 ^5,2 Chen JJ, Swope DM, Dashtipour K, Lyons KE (December 2009). „Transdermal rotigotine: a clinically innovative dopamine-receptor agonist for the management of Parkinson's disease”. Pharmacotherapy 29 (12): 1452–67. DOI:10.1592/phco.29.12.1452. PMID 19947805.

[pmid19956807-6] Davies S (September 2009). „Rotigotine for restless legs syndrome”. Drugs of Today (Barcelona, Spain : 1998) 45 (9): 663–8. DOI:10.1358/dot.2009.45.9.1399952. PMID 19956807.

[pmid16959244-7] Bertaina-Anglade V, La Rochelle CD, Scheller DK (October 2006). „Antidepressant properties of rotigotine in experimental models of depression”. European Journal of Pharmacology 548 (1-3): 106–14. DOI:10.1016/j.ejphar.2006.07.022. PMID 16959244.

[8] Cusack, N. J.; Peck, J. V.; Drugs Future 1993, 18, 1005.

[pmid18704368-9] Scheller D, Ullmer C, Berkels R, Gwarek M, Lübbert H (January 2009). „The in vitro receptor profile of rotigotine: a new agent for the treatment of Parkinson's disease”. Naunyn-Schmiedeberg's Archives of Pharmacology 379 (1): 73–86. DOI:10.1007/s00210-008-0341-4. PMID 18704368.

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