Sernyl (C1-395) in Clinical Anaesthesia

Johnstone, Michael; Evans, Viviana; Baigel, S.

doi:10.1093/bja/31.10.433

Cited by 121 publications

(32 citation statements)

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“…Binding and electrophysiological studies have demonstrated that PCP and MK-801 are superior noncompetitive inhibitors of, and have markedly higher affinity for, NMDA receptors than ketamine (Chen et al, 1959;Johnstone et al, 1959;Chen, 1965;McCarthy et al, 1965;Wong et al, 1986;MacDonald et al, 1991;Rogawski and Wenk, 2003). In addition, MK-801 block can occur across different membrane potentials, whereas PCP and ketamine inhibit NMDA receptors predominately at depolarized potentials (Halliwell et al, 1989;Dravid et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…However, a number of studies have shown that PCP and MK-801 are not effective anesthetics in rats, mice or pigeons, even at near lethal doses (Chen et al, 1959;Koek et al, 1987aKoek et al, ,b, 1988Kelland et al, 1993;Irifune et al, 2007). Therefore, contrary to the order of their impact on NMDA receptors, ketamine is a more effective anesthetic across different animal species and appears to possess a higher CNS depressant activity than PCP and MK-801 (Chen et al, 1959;Johnstone et al, 1959;Chen, 1965;Domino et al, 1965;McCarthy et al, 1965).…”

Section: Discussionmentioning

confidence: 99%

“…Error bars indicate SEM. tonic state using PCP are arousable (Johnstone et al, 1959), indicating suboptimal CNS depression, whereas patients under ketamine anesthesia do not respond to verbal commands. Furthermore, with increasing doses, PCP can induce surgically unrelated excitation (Greifenstein et al, 1958), an adverse effect absent with ketamine administration.…”

Section: Discussionmentioning

confidence: 99%

“…These drugs produce similar clinical actions, although the impact of ketamine on CNS functioning differs from that of PCP and its analogues (Greifenstein et al, 1958;Johnstone et al, 1959;Collins et al, 1960;Chen, 1965;Domino et al, 1965;Corssen and Domino, 1966). Ketamine has a lower potency, a shorter duration of action, a faster rate of induction, results in a lower incidence of adverse emergence reactions, and is an effective anesthetic across different animal species (PCP shows species selectivity).…”

Section: Introductionmentioning

confidence: 99%

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

Hevers¹,

Hadley²,

Lüddens³

et al. 2008

J. Neurosci.

121

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Phencyclidine (PCP) and ketamine are dissociative anesthetics capable of inducing analgesia, psychomimetic behavior, and a catatonic state of unconsciousness. Despite broad similarities, there are notable differences between the clinical actions of ketamine and PCP. Ketamine has a lower incidence of adverse effects and generally produces greater CNS depression than PCP. Both noncompetitively inhibit NMDA receptors, yet there is little evidence that these drugs affect GABA A receptors, the primary target of most anesthetics. ␣6␤2/3␦ receptors are subtypes of the GABA A receptor family and are abundantly expressed in granular neurons within the adult cerebellum. Here, using an oocyte expression system, we show that at anesthetically relevant concentrations, ketamine, but not PCP, modulates ␣6␤2␦ and ␣6␤3␦ receptors. Additionally, at higher concentrations, ketamine directly activates these GABA A receptors. Comparatively, dizocilpine (MK-801 [(ϩ)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate]), a potent noncompetitive antagonist of NMDA receptors that is structurally unrelated to PCP, did not produce any effect on ␣6␤2␦ receptors. Of the recombinant GABA A receptor subtypes examined (␣1␤2, ␣1␤2␥2, ␣1␤2␦, ␣4␤2␥2, ␣4␤2␦, ␣6␤2␥2, ␣6␤2␦, and ␣6␤3␦), the actions of ketamine were unique to ␣6␤2␦ and ␣6␤3␦ receptors. In dissociated granule neurons and cerebellar slice recordings, ketamine potentiated the GABAergic conductance arising from ␣6-containing GABA A receptors, whereas PCP showed no effect. Furthermore, ketamine potentiation was absent in cerebellar granule neurons from transgenic functionally null ␣6 ؊/؊ and ␦ ؊/؊ mice. These findings suggest that the higher CNS depressant level achieved by ketamine may be the result of its selective actions on ␣6␤2/3␦ receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

Hevers¹,

Hadley²,

Lüddens³

et al. 2008

J. Neurosci.

121

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“…Early investigators characterized a PCP-induced clinical syndrome of schizophrenia-like symptoms, including hallucinations, delusions, idiosyncratic and illogical thinking, poverty of speech and thought, agitation, disturbances of emotion, affect, withdrawal, decreased motivation, and dissociation (Johnstone et al 1959;Luby et al 1959;Rosenbaum et al 1959;Luby et al 1962;Corssen and Domino 1966;Bakker and Amini 1961;Davies and Beech 1960;Domino and Luby 1981). This PCP-induced syndrome can be indistinguishable from acute presentations of schizophrenia (Yesavage and Freeman 1978;Erard et al 1980).…”

mentioning

confidence: 99%

Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis

Newcomer

Farber

Jevtović-Todorović

et al. 1999

Neuropsychopharmacology

546

350

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Considerable research interest has recently been focused on the role of glutamate and related neural circuitry in the neurobiology of schizophrenia. The results of these investigations have emphasized hypofunction of glutamatergic neurons and/or the N-methyl-D-aspartate (NMDA) glutamate receptor (Tsai et al. 1995;Kim et al. 1980aKim et al. , 1980bSherman et al. 1991;Deutsch et al. 1989;Javitt and Zukin 1991;Olney 1988a;Olney 1988b;Olney and Farber 1995). An important element of several of these theoretical positions is that NMDA receptor hypofunction (NRH) produced by any mechanism can be psychotogenic. This has renewed interest in the clinical effects of NMDA glutamate receptor antagonists.Ketamine and phencyclidine (PCP) are non-competitive NMDA glutamate receptor antagonists (Zukin and Zukin 1979;Vincent et al. 1979;Lodge and Anis 1982;Lodge et al. 1987) which can produce a transient state of NRH in the brain. Early investigators characterized a PCP-induced clinical syndrome of schizophrenia-like Received March 18, 1998; revised June 19, 1998; accepted June 29, 1998. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 20 , NO . 2 NMDA Receptor Hypofunction Induced Memory Decrease 107 symptoms, including hallucinations, delusions, idiosyncratic and illogical thinking, poverty of speech and thought, agitation, disturbances of emotion, affect, withdrawal, decreased motivation, and dissociation (Johnstone et al. 1959;Luby et al. 1959;Rosenbaum et al. 1959;Luby et al. 1962;Corssen and Domino 1966;Bakker and Amini 1961;Davies and Beech 1960;Domino and Luby 1981). This PCP-induced syndrome can be indistinguishable from acute presentations of schizophrenia (Yesavage and Freeman 1978;Erard et al. 1980). Ketamine, a PCP analog still used in human anesthesia, has been reported to cause reactions similar to but not as severe as those caused by PCP, including brief, reversible "positive" and "negative" schizophrenia-like symptoms (Krystal et al. 1994;Malhotra et al. 1996). Both PCP and ketamine can exacerbate psychosis in schizophrenia Luby et al. 1962;Lahti et al. 1995a;Lahti et al. 1995b;Malhotra et al. 1997).Declarative, explicit or secondary memory and learning deficits in patients with schizophrenia occur early in the course of the illness and are quantitatively large compared with deficits in other differentiated elements of cognitive performance, showing stability "on" versus "off" antipsychotic medication and over repeated testing (Gruzelier et al. 1988;Saykin et al. 1991Saykin et al. , 1994Cannon et al. 1994). Clinical and preclinical investigations suggest the hypothesis that changes in NMDA glutamate receptor activity in patients with schizophrenia may be causally related to memory impairments found in this disorder. Relevant to this hypothesis, the activation of post-synaptic NMDA receptors is important for the induction of the activity-dependent synaptic modification called long-term potentiation (LTP) (Bliss and Collingridge 1993;Collingridge and Bliss 1995), and hippocampal LTP has been postulated to underlie cert...

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Electroencephalographic Findings in Phencyclidine Intoxication

Stockard¹,

Werner²,

Aalbers³

et al. 1976

Archives of Neurology

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The first report of electroencephalographic findings in clinically encountered phencyclidine intoxication is presented. When first seen, the patient was in a coma, initially distinguished only by nystagmus, waxy rigidity of the extremities, and an EEG with a widespread, sinusoidal theta rhythm interrupted every few seconds by periodic slow-wave complexes. The similarity of the EEG to that of deep ketamine anesthesia suggested intoxication with a ketamine-related (phenylcyclohexylamine) drug. Phencyclidine, the prototype of the phenylcyclohexylamine compounds and a widely abused hallucinogen, was subsequently identified in the urine and blood.

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Sernyl (C1-395) in Clinical Anaesthesia

Cited by 121 publications

References 0 publications

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

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

Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis

Electroencephalographic Findings in Phencyclidine Intoxication

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Sernyl (C1-395) in Clinical Anaesthesia

Cited by 121 publications

References 0 publications

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

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

Ketamine-Induced NMDA Receptor Hypofunction as a Model of Memory Impairment and Psychosis

Electroencephalographic Findings in Phencyclidine Intoxication

Contact Info

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Resources

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

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