Sökning: onr:"swepub:oai:DiVA.org:uu-518759" >
Pharmacokinetics of...
Pharmacokinetics of Novel Dopamine Transporter Inhibitor CE-123 and Modafinil with a Focus on Central Nervous System Distribution
-
- Spreitzer, Iva (författare)
- Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria.;Univ Vienna, Vienna Doctoral Sch Pharmaceut Nutr & Sport Sci, A-1090 Vienna, Austria.
-
- Keife, Josefin (författare)
- Uppsala universitet,Institutionen för farmaci
-
- Strasser, Tobias (författare)
- Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria.
-
visa fler...
-
- Kalaba, Predrag (författare)
- Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria.
-
- Lubec, Jana (författare)
- Paracelsus Med Univ, Programme Prote, A-5020 Salzburg, Austria.
-
- Neuhaus, Winfried (författare)
- AIT Austrian Inst Technol GmbH, Ctr Hlth & Bioresources, Competence Unit Mol Diagnost, A-1210 Vienna, Austria.;Danube Private Univ, Fac Med & Dent, Dept Med, A-3500 Krems, Austria.
-
- Lubec, Gert (författare)
- Paracelsus Med Univ, Programme Prote, A-5020 Salzburg, Austria.
-
- Langer, Thierry (författare)
- Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria.
-
- Wackerlig, Judith (författare)
- Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria.
-
- Loryan, Irena, Associate Professor (Docent), 1977- (författare)
- Uppsala universitet,Institutionen för farmaci
-
visa färre...
-
Univ Vienna, Dept Pharmaceut Sci, A-1090 Vienna, Austria;Univ Vienna, Vienna Doctoral Sch Pharmaceut Nutr & Sport Sci, A-1090 Vienna, Austria. Institutionen för farmaci (creator_code:org_t)
- MDPI, 2023
- 2023
- Engelska.
-
Ingår i: International Journal of Molecular Sciences. - : MDPI. - 1661-6596 .- 1422-0067. ; 24:23
- Relaterad länk:
-
https://doi.org/10.3...
-
visa fler...
-
https://uu.diva-port... (primary) (Raw object)
-
https://urn.kb.se/re...
-
https://doi.org/10.3...
-
visa färre...
Abstract
Ämnesord
Stäng
- S-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of S-CE-123 and R-modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, S-CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (K-p,K-uu,K-brain) of 0.5, compared to R-modafinil's K-p,K-uu,K-brain of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that S-CE-123 primarily localizes in the brain interstitial space, whereas R-modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (K-p,K-uu,K-cell). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with S-CE-123 having a 9.3-fold faster metabolism compared to R-modafinil. In summary, the combination of improved BBB transport and higher affinity of S-CE-123 to dopamine transporters in comparison to R-modafinil makes S-CE-123 a promising candidate for further testing for the treatment of cognitive decline.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- dopamine transporter inhibitor
- S-CE-123
- R-modafinil
- neuropharmacokinetic
- tissue distribution
- metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Spreitzer, Iva
-
Keife, Josefin
-
Strasser, Tobias
-
Kalaba, Predrag
-
Lubec, Jana
-
Neuhaus, Winfrie ...
-
visa fler...
-
Lubec, Gert
-
Langer, Thierry
-
Wackerlig, Judit ...
-
Loryan, Irena, A ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Medicinska och f ...
-
och Farmaceutiska ve ...
- Artiklar i publikationen
-
International Jo ...
- Av lärosätet
-
Uppsala universitet