A Study of a 1-Aryl Cyclo Hexyl Amine for Anesthesia*

Greifenstein, F. E.; Devault, M.; Yoshitake, J; Gajewski, J.

doi:10.1213/00000539-195809000-00007

Cited by 174 publications

(75 citation statements)

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“…Chen (1958) reported that in monkeys this drug produced primarily sedation and depression, while in rats and mice excitement was the predominant effect observed. Griefenstein, Devault, Yoshitake & Gajewski (1958) have reported that " Sernyl" is an analgesic and psychotomimetic agent in human beings. In our experiments on rats the intraperitoneal injection of 20 mg/kg caused excitation, tremors and ataxia.…”

Section: Resultsmentioning

confidence: 99%

Drug‐induced Changes in Brain Acetylcholine

Giarman

Pepeu

1962

British Journal of Pharmacology and Chemotherapy

139

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In rats, drug-induced depression of the central nervous system has been shown generally to be associated with an-elevation in level of total acetylcholine in the brain. This generalization held true for a wide variety of depressant drugs with one notable exception: the subacute administration of reserpine, with which there was an increase in cerebral acetylcholine after the first dose, but a return to normal levels after subsequent doses, despite continued depression of the animals. Reduction in the level of total acetylcholine in the brain followed the administration of certain convulsants (pentylenetetrazole and 3,5-dimethylbutylethylbarbiturate); but no change was seen after the administration of several mildly exciting agents. The notable exceptions to this generalization were atropine and scopolamine, which significantly lowered brain acetylcholine in doses producing mild excitation in only some of the animals and no gross manifestations in the rest.

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Section: Resultsmentioning

confidence: 99%

Drug‐induced Changes in Brain Acetylcholine

Giarman

Pepeu

1962

British Journal of Pharmacology and Chemotherapy

139

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“…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. Ketamine also produces a lower rate and a shorter duration of emergence reactions, such as vivid dreams and hallucinations, when compared with PCP.…”

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%

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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“…However, up to 50% of patients given PCP anesthesia developed severe intraoperative reactions characterized by agitation and hallucinations (Javitt and Zukin, 1991). The psychotic state typically lasted 12-96 h after administration of PCP but occasionally persisted for 7-10 days (Greifenstein et al, 1958;Meyer et al, 1959). Studies have shown that onset of the psychotomimetic effects of PCP is often delayed and that the effects last well beyond peak blood levels of the drug (Meltzer et al, 1972;Wessinger and Owens, 1991).…”

Section: Introductionmentioning

confidence: 99%

Synapse-Associated Protein 90/Postsynaptic Density-95-Associated Protein (SAPAP) is Expressed Differentially in Phencyclidine-Treated Rats and is Increased in the Nucleus Accumbens of Patients with Schizophrenia

Kajimoto

Sato

Lin

et al. 2003

Neuropsychopharmacol

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Phencyclidine (PCP) induces a psychotomimetic state that closely resembles schizophrenia. Therefore, PCP-treated animals can provide a model for schizophrenia. Using differential display, we identified a gene regulated by the delayed action of PCP in rat nucleus accumbens (NAcs). Sequence analysis showed that the cDNA clone obtained was identical to rat synapse-associated protein 90/ postsynaptic density-95-associated protein 1 (SAPAP1). Quantitative reverse transcriptase (RT)-PCR analysis showed that SAPAP1 mRNA had increased significantly in rat NAc (Po0.0001) and hippocampus (Po0.01) 24 h after a PCP (10 mg/kg) injection as compared to the controls. Immunoquantification using an anti-SAPAP1 antibody indicated that immunoreactivity for SAPAP1 increased significantly (Po0.05) in the NAcs of unmedicated patients with schizophrenia, as compared to the control subjects and medicated patients with schizophrenia. Our findings support the hypothesis that there is abnormal glutamatergic neurotransmission in schizophrenia and show evidence of abnormalities in the intracellular signal transduction via N-methyl-D-aspartate (NMDA) receptors.

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A Study of a 1-Aryl Cyclo Hexyl Amine for Anesthesia*

Cited by 174 publications

References 0 publications

Drug‐induced Changes in Brain Acetylcholine

Drug‐induced Changes in Brain Acetylcholine

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

Synapse-Associated Protein 90/Postsynaptic Density-95-Associated Protein (SAPAP) is Expressed Differentially in Phencyclidine-Treated Rats and is Increased in the Nucleus Accumbens of Patients with Schizophrenia

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A Study of a 1-Aryl Cyclo Hexyl Amine for Anesthesia*

Cited by 174 publications

References 0 publications

Drug‐induced Changes in Brain Acetylcholine

Drug‐induced Changes in Brain Acetylcholine

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

Synapse-Associated Protein 90/Postsynaptic Density-95-Associated Protein (SAPAP) is Expressed Differentially in Phencyclidine-Treated Rats and is Increased in the Nucleus Accumbens of Patients with Schizophrenia

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