JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Brosnan, R. J. Articles by Sonner, J. M. Search for Related Content PubMed Articles by Brosnan, R. J. Articles by Sonner, J. M. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

Ammonia Has Anesthetic Properties

Robert J. Brosnan, DVM, PhD^*, Liya Yang, PhD, Pavle S. Milutinovic, MS, Jing Zhao, MD, Michael J. Laster, DVM, Edmond I. Eger, II, MD, and James M. Sonner, MD

From the *Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, California, Department of Anesthesia and Perioperative Care, The University of California, San Francisco, California, The University of Pittsburg, Pennsylvania, and Peking Union Medical College, Beijing, China.

Address correspondence and reprint requests to James M. Sonner, MD, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to sonnerj{at}anesthesia.ucsf.edu.

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 ₁β₂ and ₁β_22s -amino butyric acid type A, ₁ 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 ₁β₂ and ₁β_22s -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.

This article has been cited by other articles:

				E. I. Eger II, D. E. Raines, S. L. Shafer, H. C. Hemmings Jr, and J. M. Sonner Is a New Paradigm Needed to Explain How Inhaled Anesthetics Produce Immobility? Anesth. Analg., September 1, 2008; 107(3): 832 - 848. [Abstract] [Full Text] [PDF]

				J. M. Sonner A Hypothesis on the Origin and Evolution of the Response to Inhaled Anesthetics Anesth. Analg., September 1, 2008; 107(3): 849 - 854. [Abstract] [Full Text] [PDF]

				L. Yang and J. M. Sonner Anesthetic-Like Modulation of Receptor Function by Surfactants: A Test of the Interfacial Theory of Anesthesia Anesth. Analg., September 1, 2008; 107(3): 868 - 874. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999