Ketamine Blocks Currents Through Mammalian Nicotinic Acetylcholine Receptor Channels by Interaction with Both the Open and the Closed State

Ketamine and its preservative, benzethonium chloride, both inhibit human recombinant α7 and α4β2 neuronal nicotinic acetylcholine receptors in Xenopus oocytes

“…In the a7 nAChR, inhibition by ketamine of the ACh response was neither voltage-nor use-dependent ( Figure 4D,F). Previous studies have demonstrated that ketamine acts via the open and closed states of the channel in the muscle type nAChRs (Scheller et al, 1996). On the NMDA receptor, ketamine acts both as an open channel blocker (Honey et al, 1985;MacDonald et al, 1991) and as an allosteric inhibitor (Orser et al, 1997).…”

“…Ketamine is also an antagonist of NMDA receptors in rat cortex (Harrison & Simmonds, 1985) and blocks these receptors at sub-clinical concentrations, by acting both as a use-dependent open channel blocker (Honey et al, 1985) and through allosteric inhibition (Orser et al, 1997). Ketamine inhibits the response to acetylcholine or nicotine in both muscle and neuronal type nAChRs (Sumikawa et al, 1983;Wachtel & Wegrzynowicz, 1992;Scheller et al, 1996;Durieux, 1995;Furuya et al, 1999;Flood & Krasowski, 2000;Friederich et al, 2000;Sasaki et al, 2000;Yamakura et al, 2000). In the case of nAChRs containing the a4 subunit, inhibition occurs at concentrations similar to those e ective in inhibiting NMDA responses (Flood & Krasowski, 2000;Friederich et al, 2000;Sasaki et al, 2000).…”

Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes

“…Ketamine acts on a variety of receptors, including nicotinic (Scheller et al, 1996) and muscarinic (Hustveit et al, 1995) receptors. Ketamine blocks peripheral and human central nervous system sodium channels (Scheller et a1., 1996), it interacts with mu (p), delta (6), and kappa (rc) opioid receptors (Smith et al, 1980;Finck and Ngai, 1982;Hustveit et al, 1995) and interacts with monoaminergic and voltage sensitive Ca--channels (Hirota and Lambert, 1996).…”

Ketamine, But Not Phencyclidine, Selectively Modulates Cerebellar GABAAReceptors Containing α6 and δ Subunits

“…These drugs also modulate the activity of nicotinic acetylcholine, muscarinic, and opioid receptors, and voltage-gated ion channels, but at significantly higher concentrations than needed to block NMDA receptors (Finck and Ngai, 1982;Ramoa et al, 1990;Hustveit et al, 1995;Hirota and Lambert, 1996;Scheller et al, 1996;Brau et al, 1997;Furuya et al, 1999;Flood and Krasowski, 2000;Yamakura et al, 2000;Schnoebel et al, 2005). Studies conducted at low doses of ketamine suggest that the inhibition of NMDA receptors results in its psychomimetic and analgesic properties (Tricklebank et al, 1987;Klepstad et al, 1990;Oye et al, 1992).…”