Ingemuva

U-Ticagrelor ungumphikisi wenoveli we-P2Y12 receptor [1].

I-Ticagrelor kubikwe ukuthi ivimbela imiphumela ye-prothrombotic ye-ADP ku-platelet ngokumelene ne-P2Y12 receptor.I-Ticagrelor ibonise ukuvinjelwa okuphelele kwe-platelet aggregation ex vivo.Ngaphezu kwalokho i-Ticagrelor iphakamise ukuvinjelwa okuncike kumthamo we-platelet aggregation kumuntu.Ngaphandle kwalokhu, u-Ticagrelor uphinde wabonisa umphikisi obopha ngomlomo, ngenkuthalo, obuyela emuva.Ngokungafani namanye ama-inhibitors, i-Ticagrelor nayo ibike ukuthi ivimbela i-P2Y12 receptor ngaphandle kokuguqulwa kwe-metabolic.Ngaphandle kwalokho, i-Ticagrelor iyi-agent yokuqala ye-thienopyridine anti-platelet futhi ikakhulukazi i-metabolized yi-CYP3A4 ne-CYP2C19 [1][2].

Izithenjwa:
[1] Zhou D1, Andersson TB, Grimm SW.Ukuhlolwa kwe-in vitro yokusebenzisana okungenzeka kwezidakamizwa nezidakamizwa nge-ticagrelor: i-cytochrome P450 yokusabela kwe-phenotyping, inhibition, induction, kanye ne-different kinetics.Izidakamizwa Metab Dispos.2011 Apr;39(4):703-10.
[2] Li Y1, Landqvist C, Grimm SW.I-Disposition kanye ne-metabolism ye-ticagrelor, i-novel P2Y12 receptor antagonist, kumagundane, amagundane, nama-marmosets.Izidakamizwa Metab Dispos.2011 Sep;39(9):1555-67.doi: 10.1124/dmd.111.039669.Epub 2011 Jun 13.

Incazelo

I-Ticagrelor (AZD6140) i-reversible oral P2Y12 receptor antagonist yokwelashwa kwe-platelet aggregation.

Ku-Vitro

I-Ticagrelor ikhuthaza ukuvinjelwa okukhulu kwe-adenosine 5'I-diphosphate (ADP)-ukukhululwa kwe-Ca2+ kuma-ished platelet ngokumelene nabanye abaphikisi be-P2Y12R.Lo mphumela owengeziwe we-ticagrelor ngaphesheya kwe-P2Y12R antagonism uyingxenye njengomphumela we-ticagrelor evimbela i-nucleoside transporter elinganayo i-1 (ENT1) kuma-platelet, okuholela ekuqoqweni kwe-adenosine ye-extracellular kanye nokusebenza kwe-Gs-coupled adenosine A2A receptors [1].Amaseli e-B16-F10 abonisa ukusebenzisana okunciphile nama-platelet avela kumagundane aphethwe yi-ticagrelor uma kuqhathaniswa namagundane aphethwe usawoti [2].

Kumamodeli we-melanoma we-B16-F10 we-intravenous and intrasplenic metastasis, amagundane aphathwa ngesilinganiso somtholampilo we-ticagrelor (10 mg / kg) abonisa ukunciphisa okuphawulwe emaphashini (84%) kanye nesibindi (86%) metastases.Ngaphezu kwalokho, ukwelashwa kwe-ticagrelor kuthuthukisa ukusinda uma kuqhathaniswa nezilwane eziphathwa nge-saline.Umphumela ofanayo ubonakala kumodeli yomdlavuza webele we-4T1, ngokunciphisa kwamaphaphu (55%) kanye nomnkantsha wamathambo (87%) ama-metastases alandela ukwelashwa kwe-ticagrelor[2].Ukuphathwa komlomo okukodwa kwe-ticagrelor (1-10 mg / kg) kubangela umphumela wokuvimbela ohlobene nomthamo ekuhlanganisweni kweplatelet.I-Ticagrelor, nge-dose ephakeme kakhulu (i-10 mg / kg) ivimbela ngokuphawulekayo ukuhlanganiswa kweplatelet ku-1 h ngemuva kwe-dosing futhi ukuvinjelwa okuphezulu kubonakala ku-4 h ngemuva kokuthatha umthamo.

Isitoreji

4°C, vikela ekukhanyeni, ogcinwe ngaphansi kwe-nitrogen

*Ku-solvent : -80°C, izinyanga ezingu-6;-20°C, inyanga engu-1 (vikela ekukhanyeni, egcinwe ngaphansi kwe-nitrogen)

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