Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Medicinska och farmaceutiska grundvetenskaper) hsv:(Farmaceutiska vetenskaper) >
Rate and extent of ...
Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution : the missing link in pharmacodynamic studies
-
- Yusof, Siti R (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Mohd Uzid, Mahathir (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Teh, Eng-Huat (författare)
- Sains USM, Ctr Herbal Standardizat, Minden, Penang, Malaysia
-
visa fler...
-
- Hanapi, Nur Aziah (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Mohideen, Mazlin (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Mohamad Arshad, Ahmad Saifuddin (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Mordi, Mohd Nizam (författare)
- Univ Sains Malaysia, HICoE Ctr Drug Res, Minden 11800, Penang, Malaysia
-
- Loryan, Irena, 1977- (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap,Translational PKPD
-
- Hammarlund-Udenaes, Margareta (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Institutionen för farmaceutisk biovetenskap,Translational PKPD
-
visa färre...
-
(creator_code:org_t)
- 2018-08-08
- 2019
- Engelska.
-
Ingår i: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 24:5, s. 935-945
- Relaterad länk:
-
https://doi.org/10.1...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Mitragyna speciosa is reported to be beneficial for the management of chronic pain and opioid withdrawal in the evolving opioid epidemic. Data on the blood-brain barrier (BBB) transport of mitragynine and 7-hydroxymitragynine, the active compounds of the plant, are still lacking and inconclusive. Here, we present for the first time the rate and the extent of mitragynine and 7-hydroxymitragynine transport across the BBB, with an investigation of their post-BBB intra-brain distribution. We utilized an in vitro BBB model to study the rate of BBB permeation of the compounds and their interaction with efflux transporter P-glycoprotein (P-gp). Mitragynine showed higher apical-to-basolateral (A-B, i.e. blood-to-brain side) permeability than 7-hydroxymitragynine. 7-Hydroxymitragynine showed a tendency to efflux, with efflux ratio (B-A/A-B) of 1.39. Both were found to inhibit the P-gp and are also subject to efflux by the P-gp. Assessment of the extent of BBB transport in vivo in rats from unbound brain to plasma concentration ratios (Kp,uu,brain ) revealed extensive efflux of both compounds, with less than 10 percent of unbound mitragynine and 7-hydroxymitragynine in plasma crossing the BBB. By contrast, the extent of intra-brain distribution was significantly different, with mitragynine having 18-fold higher brain tissue uptake in brain slice assay compared with 7-hydroxymitragynine. Mitragynine showed a moderate capacity to accumulate inside brain parenchymal cells, while 7-hydroxymitragynine showed restricted cellular barrier transport. The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Nyckelord
- 7-hydroxymitragynine
- blood-brain barrier
- extent
- mitragynine
- permeability
- pharmacokinetics
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas