Ketamine inhibits serotonin uptake in vivo.

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Martin LL, Bouchal RL, Smith DJ

Ketamine inhibits serotonin uptake in vivo.

Neuropharmacology. 1982 Feb;21(2):113-8.

PubMed ID

6460944 [ View in PubMed

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Abstract

Anesthetic (120 and 160 mg/kg. i.p.) and subanesthetic (80 mg/kg) doses of ketamine HCl were found to prevent completely the depletion of whole brain serotonin (5-HT) by p-chloramphetamine (PCA). Furthermore, ketamine HCl (160 mg/kg) completely blocked the depletion of 5-HT by PCA in every individual brain region studied (Midbrain-thalamus, hypothalamus, striatum, hippocampus and cortex). Administration of ketamine alone had no effect on brain 5-HT levels. Nialamide (a monoamine oxidase (MAO) inhibitor) and fluoxetine (a selective 5-HT uptake inhibitor) also prevented the depletion of 5-HT by PCA. However, of these three agents, only nialamide prevented the depletion of 5-HT by reserpine. These results suggest that ketamine blocks PCA-induced 5-HT depletion by inhibiting 5-HT uptake and not by inhibiting MAO. Ketamine only weakly affected either [3H]5-HT or [3H]spiroperidol binding to 5-HT1 and 5-HT2 receptors respectively even at concentrations as high as 1 mM. These data support the contention that the primary direct effect of ketamine on serotonergic systems is the blockade of 5-HT uptake and that blockade of 5-HT uptake may mediate some of the behavioral effects of ketamine, such as analgesia.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ketamine	5-hydroxytryptamine receptor 1 (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details
Ketamine	5-hydroxytryptamine receptor 2 (Protein Group)	Protein group	Humans	Unknown	Antagonist	Details