Two drugs were tested using electrochemical biosensor with immobilized acetylcholinesterase (AChE). The first was commercialized drug tacrine (known also as Cognex) used for treatment of cognitive manifestation of Alzheimer\'s disease (AD). The second one was its 7-methoxy derivate (7-MEOTA) that has not been marketed. We determined the IC50 (6.67+/-0.92)x10-7 M for tacrine and (1.66+/-1.43)x10-9 M for 7-MEOTA. In this in vitro study, 7-MEOTA acts as stronger inhibitor of AChE and in this way could be more favorable for treatment of cognitive manifestation of AD. Our study shows that biosensor technology could be used as a quick and cheap tool for testing of promising AChE inhibitors (AD drug candidates).
- MeSH
- acetylcholinesterasa chemie MeSH
- algoritmy MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- biosenzitivní techniky * MeSH
- cholinesterasové inhibitory analýza MeSH
- elektrochemie MeSH
- enzymy imobilizované chemie MeSH
- kinetika MeSH
- lidé MeSH
- nootropní látky analýza MeSH
- takrin analogy a deriváty analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 7-methoxytacrine MeSH Prohlížeč
- acetylcholinesterasa MeSH
- cholinesterasové inhibitory MeSH
- enzymy imobilizované MeSH
- nootropní látky MeSH
- takrin MeSH
- MeSH
- acetonitrily MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- chemická precipitace MeSH
- cholinesterasové inhibitory analýza krev moč MeSH
- elektroforéza kapilární metody MeSH
- koncentrace vodíkových iontů MeSH
- krevní proteiny MeSH
- lidé MeSH
- takrin analogy a deriváty analýza krev moč MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 7-methoxytacrine MeSH Prohlížeč
- acetonitrile MeSH Prohlížeč
- acetonitrily MeSH
- cholinesterasové inhibitory MeSH
- krevní proteiny MeSH
- takrin MeSH
A new capillary zone electrophoresis (CZE) method for the determination of tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7-MTHAm) in pharmaceutical and biological samples (urine and serum) was developed. Separation of all compounds by CZE was carried out using a 46.6 cm untreated fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm) and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions; 50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted 1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The methods are suitable for therapeutic drug monitoring of the drugs.
- MeSH
- Alzheimerova nemoc krev farmakoterapie moč MeSH
- cholinesterasové inhibitory analýza chemie metabolismus MeSH
- elektroforéza kapilární metody MeSH
- kalibrace MeSH
- koncentrace vodíkových iontů MeSH
- nootropní látky analýza chemie metabolismus MeSH
- senzitivita a specificita MeSH
- takrin analýza chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- cholinesterasové inhibitory MeSH
- nootropní látky MeSH
- takrin MeSH
