Inhibition of neuronal 5-HT uptake by ketamine, but not halothane, involves disruption of substrate recognition by the transporter.
The effects of halothane and ketamine on (1) serotonin (5-hydroxytryptamine; 5-HT) uptake and (2) paroxetine binding to the 5-HT transporter in neuronal membranes were determined in rat brain. Both anesthetics inhibited the uptake of [3H]5-HT by synaptosomes, but only ketamine affected binding of [3H]paroxetine to the 5-HT transporter. Saturation analysis indicated that ketamine inhibition of [3H]paroxetine binding was competitive (Ki = 18.8 microM). These results indicate that halothane and ketamine inhibit 5-HT transport by different mechanisms.
Martin
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Department of Anesthesiology, Medical College of Georgia, Augusta 30912.
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Aronstam
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D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006221:Halothane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000378:metabolism; D017374:Paroxetine; D010880:Piperidines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000493:pharmacokinetics*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D000777:Anesthetics; D014179:Neurotransmitter Uptake Inhibitors; D010880:Piperidines; D011985:Receptors, Serotonin; D012701:Serotonin; D017374:Paroxetine; D007649:Ketamine; D006221:Halothane