Distribution of enantiomers of trans-tramadol and trans-O-demethyltramadol in central nervous system of rats.
OBJECTIVE
To investigate the distribution of the enantiomers of trans-tramadol (trans-T) and its active metabolite, trans-O-demethyltramadol (M1), in the central nervous system (CNS).


METHODS
After a single ip dose of trans-T hydrochloride or M1, the rats were killed by decapitation. A high performance capillary electrophoresis (HPCE) method was used to determine the concentrations of enantiomers of trans-T and M1 in the serum and different brain tissues, including cerebrospinal fluid (CF), cerebral cortex (CC), corpus striatum (CS), hypothalamus (HY), cerebellum (CE), and medulla oblongata (MO).


RESULTS
After ip trans-T hydrochloride, the concentrations of (+)-trans-T were higher than those of (-)-trans-T in the serum and all tested brain tissues; The concentrations of (+)-M1 were lower than those of (-)-M1 in the all tested brain tissues; The concentrations of the enantiomers of trans-T and M1 were the highest in the CC, the lowest in the CF. After ip M1, the concentrations of (+)-M1 were higher than those of (-)-M1 in the serum and all tested brain tissues; The concentrations of the enantiomers of M1 were the highest in the CC, the lowest in the CF.


CONCLUSIONS
The concentrations of the enantiomers of trans-T and M1 varied in the serum and different brain tissues. The distribution of trans-T and M1 in the CNS of rats was stereoselective. The stereoselectivity in the distribution of M1 after M1 injection was different with that after trans-T injection.
Liu
H C
HC
Department of Clinical Pharmacology, Bethune International Peace Hospital, Shijiazhuang 050082, China. lhcl@heinfo.net
Wang
N
N
Liu
C S
CS
Hu
Y Q
YQ
Liu
J F
JF
Hou
Y N
YN
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D002490:Central Nervous System / Q000378:metabolism; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014018:Tissue Distribution; D014147:Tramadol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*
C080580:O-demethyltramadol; D014147:Tramadol