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

Coates, Kristen; Flood, Pamela

doi:10.1038/sj.bjp.0704315

Cited by 107 publications

(74 citation statements)

References 26 publications

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“…Although ketamine has previously been reported to inhibit e.g. NMDA-and nicotinic ACh-receptors and L-type Ca 2þ channels (Coates and Flood, 2001;Hatakeyama et al, 2001;Parsons et al, 1996;Yamakage et al, 1995;Yamakura et al, 1993Yamakura et al, , 2000, these effects are frequently observed at higher concentrations. On the other hand, MXE slightly enhanced the glutamate-evoked increase in [Ca 2þ ] i , but only in the rat cortical culture.…”

Section: Discussionmentioning

confidence: 98%

Neuropharmacological characterization of the new psychoactive substance methoxetamine

et al. 2017

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a b s t r a c tThe use of new psychoactive substances (NPS) is steadily increasing. One commonly used NPS is methoxetamine (MXE), a ketamine analogue. Several adverse effects have been reported following MXE exposure, while only limited data are available on its neuropharmacological modes of action.We investigated the effects of MXE and ketamine on several endpoints using multiple in vitro models. These included rat primary cortical cells, human SH-SY5Y cells, human induced pluripotent stem cell (hiPSC)-derived iCell ® Neurons, DopaNeurons and astrocyte co-cultures, and human embryonic kidney (HEK293) cells. We investigated effects on several neurotransmitter receptors using single cell intracellular calcium [Ca 2þ ] i imaging, effects on neuronal activity using micro-electrode array (MEA) recordings and effects on human monoamine transporters using a fluorescence-based plate reader assay.In rat primary cortical cells, 10 mM MXE increased the glutamate-evoked increase in [Ca 2þ ] i , whereas 10 mM ketamine was without effect. MXE and ketamine did not affect voltage-gated calcium channels (VGCCs), but inhibited spontaneous neuronal activity (IC 50 0.5 mM and 1.2 mM respectively). In human SH-SY5Y cells, 10 mM MXE slightly inhibited the K Our combined in vitro data provide an urgently needed first insight into the multiple modes of action of MXE. The use of different models and different (neuronal) endpoints can be complementary in pharmacological profiling. Rapid in vitro screening methods as those presented here, could be of utmost importance for gaining a first mechanistic insight to aid the risk assessment of emerging NPS.

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Section: Discussionmentioning

confidence: 98%

Neuropharmacological characterization of the new psychoactive substance methoxetamine

et al. 2017

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“…Studies investigating the sensitivity of numerous ligand-gated channels ectopically expressed in different systems to these compounds came to demonstrate that ␣7 nAChRs as well as ␤4* and ␤2* nAChRs can be inhibited noncompetitively and voltage dependently by ketamine and MK-801 (Ramoa et al, 1990;Buisson and Bertrand, 1998;Furuya et al, 1999). Concentrations of ketamine below 30 M are sufficient to reduce by 50% the activity of ␣7 and ␤4* receptors, whereas Ͼ50 M ketamine is necessary to reduce by 50% the activity of ␤2* nAChRs (Yamakura et al, 2000;Coates and Flood, 2001). Thus, it is conceivable that inhibition of ␣7 and ␤4* nAChRs by ketamine or MK-801 contributes to the dissociative anesthetic properties of these compounds (Tassonyi et al, 2002).…”

Section: Anesthetics and Psychotomimetics Interact With Neuronal Nachmentioning

confidence: 99%

Unconventional ligands and modulators of nicotinic receptors

et al. 2002

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ABSTRACT:Evidence gathered from epidemiologic and behavioral studies have indicated that neuronal nicotinic receptors (nAChRs) are intimately involved in the pathogenesis of a number of neurologic disorders, including Alzheimer's disease, Parkinson's disease, and schizophrenia. In the mammalian brain, neuronal nAChRs, in addition to mediating fast synaptic transmission, modulate fast synaptic transmission mediated by the major excitatory and inhibitory neurotransmitters glutamate and GABA, respectively. Of major interest, however, is the fact that the activity of the different subtypes of neuronal nAChR is also subject to modulation by substances of endogenous origin such as choline, the tryptophan metabolite kynurenic acid, neurosteroids, and ␤-amyloid peptides and by exogenous substances, including the so-called nicotinic allosteric potentiating ligands, of which galantamine is the prototype, and psychotomimetic drugs such as phencyclidine and ketamine. The present article reviews and discusses the effects of unconventional ligands on nAChR activity and briefly describes the potential benefits of using some of these compounds in the treatment of neuropathologic conditions in which nAChR function/expression is known to be altered.

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“…Ketamine, in addition to blocking N-methyl-D-aspartate (NMDA) receptors, has been shown to block a7 and a4b2nAChR receptors (Coates and Flood, 2001;Hilmas and Albuquerque, 2002).…”

Section: Introductionmentioning

confidence: 99%

Effects of Nicotine on Leading Saccades during Smooth Pursuit Eye Movements in Smokers and Nonsmokers with Schizophrenia

Avila

Sherr

Hong

et al. 2003

Neuropsychopharmacol

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Several studies have shown that schizophrenic patients and their biological relatives generate a greater number of leading saccades during smooth pursuit eye movement (SPEM) tasks. This abnormality may reflect a failure of cortical and/or cerebellar areas to coordinate saccadic and pursuit eye movements during visual tracking. The pharmacology of this phenomenon is not known. Here, we sought to replicate and extend the findings of Olincy et al (1998), who found that nicotine transiently reduced the number of leading saccades during SPEMs. A total of 27 subjects with schizophrenia (17 males; 14 smokers), and 25 healthy comparison subjects (nine males; 14 smokers) completed an eye-tracking task after receiving a 1.0 mg nasal spray of nicotine and during drug-free conditions. Results confirm that nicotine reduces the number of leading saccadic eye movements during visual tracking in schizophrenic patients. Baseline impairments and the beneficial effects of nicotine were not restricted to patient smokers, as nonsmoker patients exhibited the greatest number of leading saccades in the no drug condition and exhibited the most pronounced improvements after nicotine administration. Improvement in patient nonsmokers was not a function of previous smoking history. No effect of nicotine was observed in control nonsmokers. In contrast to the previous study, nicotine appeared to improve performance in control smokers. Overall, the study results support a functional role of nACh receptors in improving eye-tracking performance, and are consistent with the hypothesis, articulated by several investigators, that nACh receptor system abnormalities are responsible for a number of schizophrenia-related neurophysiological deficits.

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

Cited by 107 publications

References 26 publications

Neuropharmacological characterization of the new psychoactive substance methoxetamine

Neuropharmacological characterization of the new psychoactive substance methoxetamine

Unconventional ligands and modulators of nicotinic receptors

Effects of Nicotine on Leading Saccades during Smooth Pursuit Eye Movements in Smokers and Nonsmokers with Schizophrenia

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