BACKGROUND The role of the mechanistic target of rapamycin (mTOR) signaling in the antidepressant effects of ketamine is controversial. In addition to mTOR, extracellular signal-regulated kinase (ERK) is a key signaling molecule in prominent pathways that regulate protein synthesis. (R)-Ketamine has a greater potency and longer-lasting antidepressant effects than (S)-ketamine. Here we investiga...

AS part of the effort to develop mechanisms-based approaches to pain therapy, renewed interest has focused on the use of ketamine for treatment of acute and chronic pain. In particular, the role of N-methyl-D-aspartate (NMDA) excitatory glutamate receptors in nociceptive transmission has been established in humans. NMDA receptors participate in the development and maintenance of what can be cal...

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measur...

Ketamine, a derivative of phencyclidine that was developed in the 1960s, is an anesthetic and analgesic with hallucinogenic effects. In this paper, the pharmacological and toxicological effects of ketamine are briefly reviewed. Ketamine possesses a wide safety margin but such a therapeutic benefit is somewhat offset by its emergence phenomenon (mind-body dissociation and delirium) and hallucino...

BACKGROUND In healthy individuals, ketamine hydrochloride and amphetamine sulfate produce cognitive, behavioral, and subjective effects resembling endogenous psychoses. Studying the comparative and interactive effects of these agents may provide insights into the roles of the glutamate and monoamine systems in psychosis and cognition. OBJECTIVES To directly compare the effects of ketamine and...

BACKGROUND The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. One approach to assess the ketamine and norketamine contributions is by measuring the ketamine effect at varying ketamine and norketamine plasma...

Previously it has been shown in rats that both ketamine and morphine induced analgesia and, at larger doses, catalepsy and loss of the righting reflex, all of which were reversed by naloxone at widely different doses. Tolerance developed rapidly to either ketamine or morphine and there was cross-tolerance from ketamine to morphine. However, morphine potentiated the cataleptic effect of ketamine...

BACKGROUND Ketamine is a commonly used anesthetic, but the mechanistic basis for its clinically relevant actions remains to be determined. The authors previously showed that HCN1 channels are inhibited by ketamine and demonstrated that global HCN1 knockout mice are twofold less sensitive to hypnotic actions of ketamine. Although that work identified HCN1 channels as a viable molecular target fo...

Because ketamine and magnesium block NMDA receptor activation by distinct mechanisms of action, we hypothesized that in a model of inflammatory pain in rats the combination of ketamine and magnesium might be more effective than ketamine alone. Antinociceptive activity was assessed by the formalin test in male Wistar rats (200-250 g). Animals were injected with 100 μL of 2.5% formalin to the pla...