PMID- 18638470
OWN - NLM
STAT- MEDLINE
DCOM- 20081024
LR  - 20181201
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 592
IP  - 1-3
DP  - 2008 Sep 11
TI  - pH dependent efflux of methamphetamine derivatives and their reversal through 
      human Caco-2 cell monolayers.
PG  - 7-12
LID - 10.1016/j.ejphar.2008.06.090 [doi]
AB  - The purpose of this study was to investigate possible efflux mechanisms involved 
      in amphetamine derivative transport such as for 3,4-methylenedioxymethamphetamine 
      (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), para-methoxyamphetamine 
      (p-MA), dexamphetamine and pseudoephedrine, especially across pH gradients that 
      exist in intestinal or kidney transport. This was determined using our Caco-2 
      subclone, CLEFF9. Transport of the amphetamine derivatives was evaluated at pH 
      7.4 and pH 6/7.4+/-efflux inhibitors. Na+-H+ transporter inhibition via carbonyl 
      cyanide-4-trifluoromethoxy phenylhydrazone (FCCP), and metabolic inhibition using 
      Na-azide and Na-orthovanadate were also conducted, as well as using noradrenalin, 
      adrenalin and other inhibitors of a range of carrier mediated transport systems 
      such as histamine, organic cation transporters and dopamine carrier systems. At 
      pH 7.4, the rate of transport for dexamphetamine, pseudoephedrine and MDMA in 
      both apical to basolateral and reverse directions was all very rapid, confirming 
      extensive passive diffusion at systemic pH. However, creating a pH 6.0/7.4 
      gradient showed marked increase in basolateral to apical transport of all 
      amphetamines tested, with dexamphetamine, MDEA, MDMA and p-MA having a net efflux 
      ratio of around 16, 14, 13 and 11 respectively and this was not reversed with 
      P-glycoprotein inhibitors. Azide, FCCP, adrenalin, noradrenalin and reserpine 
      were able to reduce the efflux by 2 to 3 fold, although tetraethylammonium could 
      not. This suggested that extraneuronal monoamine transporters (hEMT) could be 
      involved. This data suggests that elevated endogenous adrenalin levels may reduce 
      amphetamine removal from the body based on these in vitro studies. Also, the use 
      of stomach acid lowering drugs could result in more rapid systemic uptake of 
      these amphetamine derivatives.
FAU - Crowe, Andrew
AU  - Crowe A
AD  - School of Pharmacy, Curtin University of Technology, Perth, Western Australia, 
      Australia. A.P.Crowe@curtin.edu.au
FAU - Diep, Susanna
AU  - Diep S
LA  - eng
PT  - Journal Article
DEP - 20080702
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Cyclosporins)
RN  - 0 (Diuretics)
RN  - 0 (Fluorescent Dyes)
RN  - 44RAL3456C (Methamphetamine)
RN  - 7DZO8EB0Z3 (Amiloride)
RN  - Q7ZP55KF3X (valspodar)
RN  - X4W3ENH1CV (Norepinephrine)
RN  - YKH834O4BH (Epinephrine)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & 
      inhibitors/metabolism
MH  - Amiloride/pharmacology
MH  - Biological Transport, Active/drug effects
MH  - Caco-2 Cells
MH  - Chromatography, High Pressure Liquid
MH  - Cyclosporins/pharmacology
MH  - Diuretics/pharmacology
MH  - Epinephrine/pharmacology
MH  - Fluorescent Dyes
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Methamphetamine/*analogs & derivatives/*metabolism
MH  - Norepinephrine/pharmacology
EDAT- 2008/07/22 09:00
MHDA- 2008/10/25 09:00
CRDT- 2008/07/22 09:00
PHST- 2008/03/14 00:00 [received]
PHST- 2008/06/18 00:00 [revised]
PHST- 2008/06/27 00:00 [accepted]
PHST- 2008/07/22 09:00 [pubmed]
PHST- 2008/10/25 09:00 [medline]
PHST- 2008/07/22 09:00 [entrez]
AID - S0014-2999(08)00704-8 [pii]
AID - 10.1016/j.ejphar.2008.06.090 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2008 Sep 11;592(1-3):7-12. doi: 10.1016/j.ejphar.2008.06.090. 
      Epub 2008 Jul 2.