Is inhibition of dopamine uptake relevant to the hypnotic action of i.v. anaesthetics?
We have examined the effects of ketamine, etomidate, propofol and thiopentone on the uptake of [3H]-dopamine into rat striatal synaptosomes. [3H]-dopamine uptake (5 min, 37 degrees C) was potently inhibited by nomifensine, a classical inhibitor of the dopamine carrier. All anaesthetics induced concentration-related inhibition of the uptake process, values for IC50 being 4.6 x 10(-6), 5.5 x 10(-5), 1.5 x 10(-4) and 2.7 x 10(-4) mol litre-1 for ketamine, etomidate, propofol and thiopentone, respectively. For all anaesthetics, inhibition of [3H]-dopamine uptake was reversible with a non-competitive profile. These data suggest that inhibition of striatal dopamine uptake may represent a relevant target site for some, but not all, i.v. anaesthetics.
Keita
H
H
Department of Anaesthesia and Inserm, Hospital Bichat, Paris, France.
Lecharny
J B
JB
Henzel
D
D
Desmonts
J M
JM
Mantz
J
J
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D007649:Ketamine; D013874:Thiopental; D004298:Dopamine; D015742:Propofol; D005045:Etomidate