Archives of Anesthesiology and Critical Care 2017. 3(2):324-333.

The Role of Neurotransmitters in Anesthesia
Atabak Najafi, Farhad Etezadi, Reza Shariat Moharari, Pejman Pourfakhr, Mohammad Reza Khajavi


General anesthetic drugs produce extensive neuronal changes in the central nervous system by enhancing inhibitory and reducing excitatory neurotransmission. The major neurotransmitters, which are thought to play a role in anesthesia, are glutamate, serotonin, norepinephrine, dopamine, acetylcholine, and GABA. The knowledge of neurotransmitters and their receptors’ function is very important in perception of anesthesia in routines practice.

The purpose of this review article is to give an overview of the different types of neurotransmitters in CNS, classification of neurotransmitters and mechanism of action of various types of neurotransmitters and their receptors.


neurotransmitters; receptors; anesthesia; central nervous system

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Campagna JA, Miller KW, Forman SA. Mechanisms of actions of inhaled anesthetics. N Engl J Med. 2003; 348(21):2110-24.

Brown EN, Purdon PL, Van Dort CJ. General Anesthesia and Altered States of Arousal: A Systems. Annu Rev Neurosci. 2011; 34:601-628.

Whishaw, Bryan Kolb, Ian Q. An introduction to brain and behavior. 2014;4th ed. New York, NY: Worth Publishers. pp. 150–151

Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA, Hudspeth. 2013 Principles of Neural Science. New York: McGraw Hill. p. 229

Patton KT. Anatomy and physiology. Elsevier Health Sciences; 2015 Feb 10.

M. Sheng, C. Hoogenraad; Hoogenraad. Annual Review of Biochemistry. 2006;76: 823–47.

Gitler D, Takagishi Y, Feng J, Ren Y, Rodriguiz RM, Wetsel WC, Greengard P, Augustine GJ. Different presynaptic roles of synapsins at excitatory and inhibitory synapses. Journal of Neuroscience. 2004 Dec 15;24 (50):11368-80.

Pocock JM, Kettenmann H. Neurotransmitter receptors on microglia. Trends in neurosciences. 2007. 31;30 (10):527-35.

Snyder SH. Drug and neurotransmitter receptors in the brain. Science. 1984 Apr 6;224:22-32.

Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Ligand-gated ion channels: mechanisms underlying ion selectivity. Progress in biophysics and molecular biology. 2004 Oct 31;86 (2):161-204.

Catterall WA. Structure and function of voltage-gated ion channels. Annual review of biochemistry. 1995 Jul;64 (1):493-531.

Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A, Filipek S. Action of molecular switches in GPCRs--theoretical and experimental studies. Current Medicinal Chemistry.2012; 19 (8): 1090–109.

De Vries L, Farquhar MG, Zheng B, Fischer T, Elenko E (2000). "The regulator of G protein signaling family". Annu. Rev. Pharmacol. Toxicol. 40: 235–271.

Gilman A.G. (1987). "G Proteins: Transducers of Receptor-Generated Signals". Annual Review of Biochemistry. 56: 615–649.

Son Y. Molecular mechanisms of general anesthesia. Korean Journal of Anesthesiology. 2010;59 (1):3-8.

Hemmings HC., Jr Sodium channels and the synaptic mechanisms of inhaled anaesthetics. Br J Anaesth. 2009;103:61–69

Tuček, S. "Choline acetyltransferase and the synthesis of acetylcholine." The Cholinergic Synapse. Springer Berlin Heidelberg, 1988. 125-165.

Kleinz MJ, Spence I. The pharmacology of the autonomic nervous system. Small animal clinical pharmacology. 2nd Ed. Philadelphia: Saunders Elsevier, USA. 2008:59-82.

Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012 Oct 4;76 (1):116-29.

Miyazawa A, Fujiyoshi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003. 26; 423 (6943):949-55.

Melroy-Greif, W. E., Stitzel, J. A., & Ehringer, M. A.Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use. Genes, Brain, and Behavior.2016; 15 (1), 89–107.

Haga T. Molecular properties of muscarinic acetylcholine receptors. Proceedings of the Japan Academy, Series B. 2013;89 (6):226-56.

Tassonyi E, Charpantier E, Muller D, Dumont L, Bertrand D. The role of nicotinic acetylcholine receptors in the mechanisms of anesthesia. Brain research bulletin. 2002 Jan 15;57 (2):133-50.

Wong SM, Sonner JM, Kendig JJ. Acetylcholine receptors do not mediate isoflurane’s actions on spinal cord in vitro. Anesthesia & Analgesia. 2002 Jun 1;94 (6):1495-9.

Liu L, Li W, Wei K, Cao J, Luo J, Wang B, Min S. Synergistic effect of sevoflurane and isoflurane on inhibition of the adult-type muscle nicotinic acetylcholine receptor by rocuronium. Journal of anesthesia. 2013 Jun 1;27 (3):351-8.

Li K, Xu E. The role and the mechanism of γ-aminobutyric acid during central nervous system development. Neuroscience bulletin. 2008 Jun 1;24 (3):195.

Petroff OA. Book review: GABA and glutamate in the human brain. The Neuroscientist. 2002 Dec;8 (6):562-73.

Macdonald RL, Olsen RW. GABA receptor channels. Annu Rev Neurosci 1994;17: 569–602.

Bormann J. The ‘ABC’of GABA receptors. Trends in Pharmacological Sciences. 2000 Jan 1;21 (1):16-9.

Forman SA, Miller KW. Anesthetic Sites and Allosteric Mechanisms of Action on Cys-loop Ligand-gated Ion Channels. Canadian journal of anaesthesia 2011;58 (2):191-205.

Fritschy JM, Panzanelli P. GABAA receptors and plasticity of inhibitory neurotransmission in the central nervous system. European Journal of Neuroscience. 2014 Jun 1;39 (11):1845-65.

Olsen, R.W., Sieghart, W. GABA A receptors: subtypes provide diversity of function and pharmacology. Neurophar- macology.2009; 56, 141-148.

Chalifoux JR, Carter AG. GABAB receptor modulation of synaptic function. Current opinion in neurobiology. 2011;21 (2):339-344.

McGaugh, J.L., Izquierdo, I. The contribution of pharmacology to research on the mechanisms of memory formation. Trends Pharmacol. Sci.2000; 21, 208-210.

Garcia PS, Kolesky SE, Jenkins A. General Anesthetic Actions on GABAA Receptors. Current Neuropharmacology. 2010;8 (1):2-9.

Trudell JR, Bertaccini E, MacIver BM. Teaching an Old GABA Receptor New Tricks. Anesthesia and analgesia. 2012;115 (2):270-273.

Aragón C1, López-Corcuera B. Structure, function and regulation of glycine neurotransporters. Eur J Pharmacol. 2003 Oct 31;479 (1-3):249-62.

Sibilla S, Ballerini L. GABAergic and glycinergic interneuron expression during spinal cord development: dynamic interplay between inhibition and excitation in the control of ventral network outputs. Progress in neurobiology. 2009 Sep 30;89 (1):46-60.

Kramer F, Griesemer D, Bakker D, Brill S, Franke J, Frotscher E, Friauf E. Inhibitory glycinergic neurotransmission in the mammalian auditory brainstem upon prolonged stimulation: short-term plasticity and synaptic reliability. Inhibitory Function in Auditory Processing. 2015 Oct 28.

Cummings KA1, Popescu GK2. Glycine-dependent activation of NMDA receptors. J Gen Physiol. 2015 Jun;145 (6):513-27.

Harvey RJ, Yee BK. Glycine transporters as novel therapeutic targets in schizophrenia, alcohol dependence and pain. Nature reviews Drug discovery. 2013 Nov 1;12 (11):866-85.

Petrat F, Boengler K, Schulz R, de Groot H. Glycine, a simple physiological compound protecting by yet puzzling mechanism (s) against ischaemia–reperfusion injury: current knowledge. British Journal of Pharmacology. 2012;165 (7):2059-2072.

Breitinger HG. Glycine receptors. eLS. 2014.

Pérez-Torres I, María Zuniga-Munoz A, Guarner-Lans V. Beneficial Effects of the Amino Acid Glycine. Mini reviews in medicinal chemistry. 2017 Jan 1;17 (1):15-32.

Meldrum BS1.Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr. 2000 Apr;130 (4S Suppl):1007S-15S.

Hawkins RA, Viña JR. How Glutamate Is Managed by the Blood–Brain Barrier. Cooper AJL, Jeitner TM, eds. Biology. 2016;5 (4):37. doi:10.3390/biology5040037.

Smith QR. "Transport of glutamate and other amino acids at the blood-brain barrier". J. Nutr. 2000;130 (4S Suppl): 1016S–22S.

Hawkins RA1, Viña JR2. How Glutamate Is Managed by the Blood-Brain Barrier. Biology (Basel). 2016 Oct 8;5 (4). pii: E37.

McEntee, William J., and Thomas H. Crook. "Glutamate: its role in learning, memory, and the aging brain." Psychopharmacology 111.4 (1993): 391-401.

Zhou, Y., and N. C. Danbolt. "Glutamate as a neurotransmitter in the healthy brain." Journal of neural transmission 121.8 (2014): 799-817.

Niciu MJ, Kelmendi B, Sanacora G. Overview of Glutamatergic Neurotransmission in the Nervous System. Pharmacology, Biochemistry, and Behavior. 2012;100 (4):656-664. doi:10.1016/j.pbb.2011.08.008.

Westphalen RI, Desai KM, Hemmings HC. Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane. British journal of anaesthesia. 2012 Dec 4:aes448.

Wood PL. The NMDAR complex: a long and winding road to therapeutics. IDrugs. 2005;8:229.

Parsons MP, Raymond LA. Extrasynaptic NMDA receptor involvement in central nervous system disorders. Neuron. 2014 Apr 16;82 (2):279-93.

Hardingham GE, Bading H. Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders. Nature Reviews Neuroscience. 2010 Oct 1;11 (10):682-96.

Vyklicky V, Korinek M, Smejkalova T, Balik A, Krausova B, Kaniakova M, Lichnerova K, Cerny J, Krusek J, Dittert I, Horak M. Structure, function, and pharmacology of NMDA receptor channels. Physiological Research. 2014 Jan 1;63:S191.

Ogden KK, Traynelis SF. New advances in NMDA receptor pharmacology. Trends in pharmacological sciences. 2011 Dec 31;32 (12):726-33.

Gonda X. Basic pharmacology of NMDA receptors. Curr Pharm Des. 2012;18 (12):1558-67.

Defining the role of NMDA receptors in anesthesia: Are we there yet? European Journal of Pharmacology 723 (2014) 29–37

Berger M, Gray JA, Roth BL; Gray; Roth. The expanded biology of serotonin. Annu. Rev. Med.2009; 60: 355–66.

Zhou M, Engel K, Wang J; Engel; Wang. Evidence for significant contribution of a newly identified monoamine transporter (PMAT) to serotonin uptake in the human brain.2007; Biochem. Pharmacol. 73 (1): 147–54.

Gershon MD. 5-Hydroxytryptamine (serotonin) in the gastrointestinal tract. Current opinion in endocrinology, diabetes, and obesity. 2013;20 (1):14-21. doi:10.1097/MED.0b013e32835bc703.

Kim, D., & Camilleri, M. (2000). Serotonin: A mediator of the brain-gut connection. The American Journal of Gastroenterology, 95 (10), 2698-2709.

Johansen S, Iceman K, Iceman C, Taylor B, Harris M. Isoflurane causes concentration-dependent inhibition of medullary raphé 5-HT neurons in situ. Autonomic neuroscience : basic & clinical. 2015;193:51-56.

Wacker D, Wang C, Katritch V, et al. Structural Features for Functional Selectivity at Serotonin Receptors. Science (New York, NY). 2013;340 (6132):615-619.

Williams, Freddie M., and Timothy J. Turner. "Adrenergic pharmacology." Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy (2008): 129.

Björklund A, Dunnett SB. Dopamine neuron systems in the brain: an update". Trends in Neurosciences.2007; 30 (5): 194–202

Rice ME, Patel JC, Cragg SJ "Dopamine release in the basal ganglia". Neuroscience. 198: 112–37.

Beaulieu JM, Gainetdinov RR. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacological reviews. 2011 Mar 1;63 (1):182-217.

aylor NE, Chemali JJ, Brown EN, Solt K. Activation of D1 dopamine receptors induces emergence from isoflurane general anesthesia. Anesthesiology. 2013; 118: 30–39.

Solt K, Van Dort CJ, Chemali JJ, Taylor NE, Kenny JD, Brown EN. Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia. Anesthesiology. 2014; 121: 311–319.

Carey RJ, Huston JP, Muller CP. Pharmacological € inhibition of dopamine and serotonin activity blocks spontaneous and cocaine-activated behavior. Prog Brain Res 2008;172:347–360.

Westphalen, R. I., K. M. Desai, and H. C. Hemmings. "Presynaptic inhibition of the release of multiple major central nervous system neurotransmitter types by the inhaled anaesthetic isoflurane." British journal of anaesthesia.2012: aes448.

Sara SJ. Locus Coeruleus in time with the making of memories".2015; Curr. Opin. Neurobiol. 35: 87–94

Rang HP, Ritter JM, Flower R, Henderson G. Noradrenergic transmission.2014; Rang & Dale's Pharmacology. Elsevier Health Sciences. pp. 177–196

Leung LS, Luo T, Ma J, Herrick I. Brain areas that influence general anesthesia. Progress in neurobiology. 2014 Nov 30;122:24-44.

Cahill L, Alkire MT. Epinephrine enhancement of human memory consolidation: interaction with arousal at encoding". Neurobiology of Learning and Memory.2003; 79 (2): 194–8

Haas HL, Sergeeva OA, Selbach O. Histamine in the nervous system. Physiological reviews. 2008 Jul 1;88 (3):1183-241.

Lee KH, Broberger C, Kim U, McCormick DA. Histamine modulates thalamocortical activity by activating a chloride conductance in ferret perigeniculate neurons. Proc Natl Acad Sci USA 101: 6716–6721, 2004.

Passani MB, Panula P, Lin JS. Histamine in the brain. Frontiers in systems neuroscience. 2014;8.

Saper CB, Scammell TE, Lu J: Hypothalamic regulation of sleep and circadian rhythms. Nature 2005; 437:1257– 63

Luo T, Leung LS. Involvement of tuberomamillary histaminergic neurons in isoflurane anesthesia. The Journal of the American Society of Anesthesiologists. 2011 Jul 1;115 (1):36-43.

Zecharia AY, Yu X, Gotz T, et al: GABAergic inhibition of histaminergic neurons regulates active waking but not the sleepwake

Mahdy AM, Webster NR. Histamine and antihistamines. Anaesthesia & Intensive Care Medicine. 2014 31;15 (5):250-5.


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