Respiratory effects of glutamate receptor antagonists in neonate and adult mammals

European Journal of Pharmacology
V BordayM Denavit-Saubié

Abstract

We determined the conditions (immaturity, species, anesthesia, receptor blockade selectivity) under which glutamate receptor blockade produces respiratory depression in mammals. In unrestrained 0- to 2-day-old neonate and adult mice and cats, ventilation was measured by the barometric method, before and after separate or sequential administration of a non-NMDA receptor antagonist, NBQX (2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline, 2-200 mg kg(-1) in mice, 10-40 mg kg(-1) in cats), and a NMDA receptor antagonist, dizocilpine (3 mg kg(-1) in mice, 0.15-1.0 mg kg(-1) in cats). NBQX or dizocilpine alone did not decrease ventilation in awake adults, but NBQX strongly depressed ventilation in neonate awake mice and in adult anesthetized animals. Given together, dizocilpine and NBQX always profoundly depressed ventilation by producing a lethal apnea in neonate mice, and an apneustic pattern of breathing in adults of both species and in neonate cats. We conclude that blockade of either NMDA or non-NMDA receptors is innocuous in awake adults. The factors which may potentiate respiratory depression are (1) anesthesia, (2) immaturity, and (3) combined blockade of both receptors types. The mechanism of depression is species-depend...Continue Reading

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Citations

May 24, 2005·Respiratory Physiology & Neurobiology·Karen A Waters, Rita Machaalani
Jun 14, 2005·Respiratory Physiology & Neurobiology·Narong Simakajornboon, Teeradej Kuptanon
Sep 1, 2000·Respiration Physiology·G FortinJ Champagnat
Apr 2, 2003·Pharmacology, Biochemistry, and Behavior·Vincent L H HoffmannTheo F Meert
Mar 28, 2003·Respiratory Physiology & Neurobiology·Michael B Harris, William K Milsom
Aug 5, 2009·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Michael Mörschel, Mathias Dutschmann
Nov 3, 2004·Respiratory Physiology & Neurobiology·Gérard HilaireMichelle Bévengut
Jun 10, 2004·Respiratory Physiology & Neurobiology·Joyce A BoonW K Milsom
Mar 4, 2000·The Journal of Physiology·M S SiniaiaC S Poon
Sep 12, 2009·Respiratory Physiology & Neurobiology·Daniel A N SilvermanGeorge D Olsen
May 14, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Stephen R ReevesDavid Gozal
Aug 20, 2005·Journal of Applied Physiology·Stephen G Reid, Frank L Powell
Feb 9, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·G M WhitneyD Gozal
Oct 23, 2002·Journal of Applied Physiology·Michelle McGuireLiming Ling
Jun 23, 2009·Journal of Pharmacological Sciences·Saori TsunekawaAkira Haji
Jul 21, 2009·Respiratory Physiology & Neurobiology·Akiko Arata

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