Ammonia has anesthetic properties

Robert J Brosnan, Liya Yang, Pavle S. Milutinovic, Jing Zhao, Michael J. Laster, Edmond I. Eger, James M. Sonner

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: A recent theory of anesthesia predicts that some endogenous compounds should have anesthetic properties. This theory raises the possibility that metabolites that are profoundly elevated in disease may also exert anesthetic effects. Because in pathophysiologic concentrations, ammonia reversibly impairs memory, consciousness, and responsiveness to noxious stimuli in a manner similar to anesthetics, we investigated whether ammonia had anesthetic properties. METHODS: The effect of ammonia was studied on α1β2 and α1β2γ2s γ-amino butyric acid type A, α1 glycine, and NR1/NR2A N-methyl-d-aspartate receptors, and the two-pore domain potassium channel TRESK. Channels were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. The immobilizing effect of ammonia in rats was evaluated by determining the reduction in isoflurane minimum alveolar concentration produced by IV infusion of ammonium chloride. The olive oil-water partition coefficient was measured to determine whether free ammonia (NH3) followed the Meyer-Overton relation. RESULTS: Ammonia positively modulated TRESK channels and glycine receptors. No effect was seen on α1β2 and α1β2γ2s γ-amino butyric acid type A receptors or NR1/NR2A N-methyl-d-aspartate receptors. Ammonia reversibly decreased the requirement for isoflurane, with a calculated immobilizing EC50 of 1.6 ± 0.1 mM NH4Cl. The Ostwald olive oil-water partition coefficient for NH3 was 0.018. At a pH of 7.4, and at the anesthetic EC50, the NH3 concentration in bulk olive oil is 0.42 μM, approximately five orders of magnitude less than observed by anesthetics that follow the Meyer-Overton relation. CONCLUSIONS: These findings support the hypothesis that ammonia has anesthetic properties. Bulk oil concentration did not predict the potency of ammonia.

Original languageEnglish (US)
Pages (from-to)1430-1433
Number of pages4
JournalAnesthesia and Analgesia
Volume104
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Ammonia
Anesthetics
Butyric Acid
Isoflurane
Glycine Receptors
Ammonium Chloride
Water
Potassium Channels
Xenopus laevis
Consciousness
Constriction
Glycine
Oocytes
Electrodes
Oils
Anesthesia

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Brosnan, R. J., Yang, L., Milutinovic, P. S., Zhao, J., Laster, M. J., Eger, E. I., & Sonner, J. M. (2007). Ammonia has anesthetic properties. Anesthesia and Analgesia, 104(6), 1430-1433. https://doi.org/10.1213/01.ane.0000264072.97705.0f

Ammonia has anesthetic properties. / Brosnan, Robert J; Yang, Liya; Milutinovic, Pavle S.; Zhao, Jing; Laster, Michael J.; Eger, Edmond I.; Sonner, James M.

In: Anesthesia and Analgesia, Vol. 104, No. 6, 06.2007, p. 1430-1433.

Research output: Contribution to journalArticle

Brosnan, RJ, Yang, L, Milutinovic, PS, Zhao, J, Laster, MJ, Eger, EI & Sonner, JM 2007, 'Ammonia has anesthetic properties', Anesthesia and Analgesia, vol. 104, no. 6, pp. 1430-1433. https://doi.org/10.1213/01.ane.0000264072.97705.0f
Brosnan RJ, Yang L, Milutinovic PS, Zhao J, Laster MJ, Eger EI et al. Ammonia has anesthetic properties. Anesthesia and Analgesia. 2007 Jun;104(6):1430-1433. https://doi.org/10.1213/01.ane.0000264072.97705.0f
Brosnan, Robert J ; Yang, Liya ; Milutinovic, Pavle S. ; Zhao, Jing ; Laster, Michael J. ; Eger, Edmond I. ; Sonner, James M. / Ammonia has anesthetic properties. In: Anesthesia and Analgesia. 2007 ; Vol. 104, No. 6. pp. 1430-1433.
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AB - BACKGROUND: A recent theory of anesthesia predicts that some endogenous compounds should have anesthetic properties. This theory raises the possibility that metabolites that are profoundly elevated in disease may also exert anesthetic effects. Because in pathophysiologic concentrations, ammonia reversibly impairs memory, consciousness, and responsiveness to noxious stimuli in a manner similar to anesthetics, we investigated whether ammonia had anesthetic properties. METHODS: The effect of ammonia was studied on α1β2 and α1β2γ2s γ-amino butyric acid type A, α1 glycine, and NR1/NR2A N-methyl-d-aspartate receptors, and the two-pore domain potassium channel TRESK. Channels were expressed in Xenopus laevis oocytes and studied using two-electrode voltage clamping. The immobilizing effect of ammonia in rats was evaluated by determining the reduction in isoflurane minimum alveolar concentration produced by IV infusion of ammonium chloride. The olive oil-water partition coefficient was measured to determine whether free ammonia (NH3) followed the Meyer-Overton relation. RESULTS: Ammonia positively modulated TRESK channels and glycine receptors. No effect was seen on α1β2 and α1β2γ2s γ-amino butyric acid type A receptors or NR1/NR2A N-methyl-d-aspartate receptors. Ammonia reversibly decreased the requirement for isoflurane, with a calculated immobilizing EC50 of 1.6 ± 0.1 mM NH4Cl. The Ostwald olive oil-water partition coefficient for NH3 was 0.018. At a pH of 7.4, and at the anesthetic EC50, the NH3 concentration in bulk olive oil is 0.42 μM, approximately five orders of magnitude less than observed by anesthetics that follow the Meyer-Overton relation. CONCLUSIONS: These findings support the hypothesis that ammonia has anesthetic properties. Bulk oil concentration did not predict the potency of ammonia.

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