Dizocilpin

Dizocilpin
(IUPAC) ime
	(+)-5-metil-10,11- dihidro-5H-dibenzo[a,d]ciklohepten-5,10-imin maleat
Klinički podaci
Identifikatori
CAS broj	77086-21-6
ATC kod	nije dodeljen
PubChem	180081
ChemSpider	156718
UNII	7PY8KH681I
ChEMBL	CHEMBL284237
Hemijski podaci
Formula	C16H15N
Mol. masa	221,297 g/mol
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C16H15N/c1-16-13-8-4-2-6-11(13)10-15(17-16)12-7-3-5-9-14(12)16/h2-9,15,17H,10H2,1H3/t15-,16+/m1/s1 ; Key: LBOJYSIDWZQNJS-CVEARBPZSA-N
Fizički podaci
Tačka topljenja	68.75 °C (156 °F)
Farmakokinetički podaci
Bioraspoloživost	?
Metabolizam	?
Poluvreme eliminacije	?
Izlučivanje	?
Farmakoinformacioni podaci
Trudnoća	?(AU) ?(US)
Pravni status
Način primene	Oralno, IM

Dizocilpin (INN) (MK-801) je nekompetitivni antagonist N-metil-d-aspartat (NMDA) receptora, glutamatnog receptor. Glutamat je primarni pobuđivački neurotransmiter mozga. Kanal je normalno blokiran jonom magnezijuma i neophodna je depolarizacija neurona da se ukloni magnezijum i omogući glutamatu da otvori kanal, nakon čega dolazi do unosa kalcijuma, što dovodi do naknadne depolarizacije.^[5] MK-801 se vezuje unutar jonskog kanala receptora na nekoliko mesta vezivanja PCP-a čime se sprečava unos jona, uključujući kalcijuma (Ca²⁺), kroz kanal. Dizocilpin blokira NMDA receptore u upotrebnom i od napona zavisnom maniru, pošto kanal mora da bude otvoren da bi se lek vezao. Lek deluje kao potentan antikonvulsant i verovatno ima disocijativna anestetička svojstva, ali nema kliničku primenu za te svrhe jer može da uzrokuje povrede mozga. MK-801 je takođe asociran sa brojnim nuspojavama, među kojima su kognitivni poremećaj i niz psihotičkih reakcija. On isto tako inhibira indukciju dugotrajne potencijacije.^[6]

Za dizocilpin je nađeno da deluje kao antagonist nikotinskog acetilholinskog receptora.^[7]^[8]^[9] Isto tako je pokazano da se vezuje i inhibira serotoninske i dopaminske trasportere.^[10]^[11]

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
↑ Foster AC, Fagg GE (1987). „Neurobiology. Taking apart NMDA receptors”. Nature 329 (6138): 395–6. DOI:10.1038/329395a0. PMID 2443852.
↑ Coan EJ, Saywood W, Collingridge GL (September 1987). „MK-801 blocks NMDA receptor-mediated synaptic transmission and long term potentiation in rat hippocampal slices”. Neurosci. Lett. 80 (1): 111–4. DOI:10.1016/0304-3940(87)90505-2. PMID 2821457.
↑ Ramoa AS, Alkondon M, Aracava Y, et al. (July 1990). „The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels”. The Journal of Pharmacology and Experimental Therapeutics 254 (1): 71–82. PMID 1694895.
↑ Amador M, Dani JA (March 1991). „MK-801 inhibition of nicotinic acetylcholine receptor channels”. Synapse 7 (3): 207–15. DOI:10.1002/syn.890070305. PMID 1715611.
↑ Briggs CA, McKenna DG (April 1996). „Effect of MK-801 at the human alpha 7 nicotinic acetylcholine receptor”. Neuropharmacology 35 (4): 407–14. DOI:10.1016/0028-3908(96)00006-8. PMID 8793902.
↑ Iravani MM, Muscat R, Kruk ZL (June 1999). „MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry”. Synapse 32 (3): 212–24. DOI:10.1002/(SICI)1098-2396(19990601)32:3<212::AID-SYN7>3.0.CO;2-M. PMID 10340631.
↑ Clarke PB, Reuben M (January 1995). „Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter”. British Journal of Pharmacology 114 (2): 315–22. PMC 1510234. PMID 7881731.

Literatura

Wong EH, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL (September 1986). „The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist”. Proc Natl Acad Sci USA 83 (18): 7104–8. DOI:10.1073/pnas.83.18.7104. PMC 386661. PMID 3529096.

Povezano

[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

[5] Foster AC, Fagg GE (1987). „Neurobiology. Taking apart NMDA receptors”. Nature 329 (6138): 395–6. DOI:10.1038/329395a0. PMID 2443852.

[6] Coan EJ, Saywood W, Collingridge GL (September 1987). „MK-801 blocks NMDA receptor-mediated synaptic transmission and long term potentiation in rat hippocampal slices”. Neurosci. Lett. 80 (1): 111–4. DOI:10.1016/0304-3940(87)90505-2. PMID 2821457.

[pmid1694895-7] Ramoa AS, Alkondon M, Aracava Y, et al. (July 1990). „The anticonvulsant MK-801 interacts with peripheral and central nicotinic acetylcholine receptor ion channels”. The Journal of Pharmacology and Experimental Therapeutics 254 (1): 71–82. PMID 1694895.

[pmid1715611-8] Amador M, Dani JA (March 1991). „MK-801 inhibition of nicotinic acetylcholine receptor channels”. Synapse 7 (3): 207–15. DOI:10.1002/syn.890070305. PMID 1715611.

[pmid8793902-9] Briggs CA, McKenna DG (April 1996). „Effect of MK-801 at the human alpha 7 nicotinic acetylcholine receptor”. Neuropharmacology 35 (4): 407–14. DOI:10.1016/0028-3908(96)00006-8. PMID 8793902.

[pmid10340631-10] Iravani MM, Muscat R, Kruk ZL (June 1999). „MK-801 interaction with the 5-HT transporter: a real-time study in brain slices using fast cyclic voltammetry”. Synapse 32 (3): 212–24. DOI:10.1002/(SICI)1098-2396(19990601)32:3<212::AID-SYN7>3.0.CO;2-M. PMID 10340631.

[pmid-11] Clarke PB, Reuben M (January 1995). „Inhibition by dizocilpine (MK-801) of striatal dopamine release induced by MPTP and MPP+: possible action at the dopamine transporter”. British Journal of Pharmacology 114 (2): 315–22. PMC 1510234. PMID 7881731.

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