Effective pharmacological treatments for tinnitus have proven elusive. Emerging evidence suggests that dysregulation of cochlear N-methyl-D-aspartate (NMDA) receptors may underlie aberrant excitation of the auditory nerve, which in turn is perceived as tinnitus. The blocking of these receptors thus represents a promising therapeutic approach. In a recent phase I/II clinical trial, the safety and local tolerance of intratympanic injections of the NMDA receptor antagonist AM-101 was evaluated for the first time in humans. The results from the double-blind, randomized, placebo-controlled study show that intratympanically injected AM-101 was well tolerated by study participants, and provided the first indications of therapeutic efficacy.

Alzamil KS, Linthicum FH Jr: Extraneous round window membranes and plugs: possible effect on intratympanic therapy. Ann Otol Rhinol Laryngol 2000;109:30–32.
Andersson G, Vretblad P, Larsen HC, Lyttkens L: Longitudinal follow-up of tinnitus complaints. Arch Otolaryngol Head Neck Surg 2001;127:175–179.
Araújo MF, Oliveira CA, Bahmad FM: Intratympanic dexamethasone injections as a treatment for severe, disabling tinnitus: does it work? Arch Otolaryngol Head Neck Surg 2005;131:113–117.
Biesinger E, Heiden C, Greimel V, Lendle T, Hoeing R, Albegger K: Strategies in ambulatory treatment of tinnitus. HNO 1998;46:157–169.
Chan Y: Tinnitus: etiology, classification, characteristics, and treatment. Discov Med 2009;42:133–136.
Chen Z, Duan M, Lee H, Ruan R, Ulfendahl M: Pharmacokinetics of caroverine in the inner ear and its effects on cochlear function after systemic and local administrations in Guinea pigs. Audiol Neurotol 2003;8:49–56.
Darlington CL, Smith PF: Drug treatments for tinnitus. Prog Brain Res 2007;166:249–262.
Davis PB, Paki B, Hanley PJ: Neuromonics Tinnitus Treatment: third clinical trial. Ear Hear 2007;28:242–259.
DeLucchi E: Transtympanic pilocarpine in tinnitus. Int Tinnitus J 2000;6:37–40.
Dobie RA: A review of randomized clinical trials in tinnitus. Laryngoscope 1999;109:1202–1211.
Dobie RA: Clinical trials and drug therapy for tinnitus; in Snow JB (ed): Tinnitus – Theory and Management. Hamilton, BC Decker, 2004, pp 266–277.
Dodson K, Sismanis A: Intratympanic perfusion for the treatment of tinnitus. Otolaryngol Clin North Am 2004;37:991–1000.
Eggermont JJ, Roberts LE: The neuroscience of tinnitus. Trends Neurosci 2004;27:676–682.
Ehrenberger K: Topical administration of caroverine in somatic tinnitus treatment: proof-of-concept study. Int Tinnitus J 2005;11:34–37.
Engström B, Bjurström S, Jansson B, Engström H, Angelborg C: An ultrastructural and functional study of the inner ear after administration of hyaluronan into the middle ear of the guinea pig. Acta Otolaryngol Suppl 1987;442:66–71.
Greimel KV, Leibetseder M, Unterrainer J, Biesinger E, Albegger K: Der Tinnitus-Beeinträchtigungs-Fragebogen (TBF-12) – Übersetzung und Adaptation. Verhaltensther Verhaltensmed 2000;21:39–49.
Guitton M, Dudai Y: Blockade of cochlear NMDA receptors prevents long-term tinnitus during a brief consolidation window after acoustic trauma. Neural Plast 2007;2007:80904.
Guitton MJ, Caston J, Ruel J, Johnson RM, Pujol R, Puel JL: Salicylate induces tinnitus through activation of cochlear NMDA receptors. J Neurosci 2003;23:3944–3952.
Jastreboff PW, Hazell JWP, Graham RL: Neurophysiological model of tinnitus: dependence of the minimal masking level on treatment outcome. Hear Res 1994;80:216–232.
Kemp JA, McKernan RM: NMDA receptor pathways as drug targets. Nat Neurosci 2002;5(suppl):1039–1042.
Knipper M, Zimmermann U, Müller M: Molecular aspects of tinnitus. Hear Res 2010;266:60–69.
Langguth B, Salvi R, Elgoyhen AB: Emerging pharmacotherapy of tinnitus. Expert Opin Emerg Drugs 2009;14:687–702.
Lustig LR: The history of intratympanic drug therapy in otology. Otolaryngol Clin North Am 2004;37:1001–1017.
Meikle MB, Stewart BJ, Griest SE, Henry JA: Tinnitus outcomes assessment. Trends Amplif 2008;12:223–235.
Meikle MB, Stewart BJ, Griest SE, Martin WH, Henry JA, Abrams HB, McArdle R, Newman CW, Sandridge SA: Assessment of tinnitus: measurement of treatment outcomes. Prog Brain Res 2007;166:511–521.
Mitchell JF: Intratympanic injection for tinnitus aurium. J Laryngol Otol 1950;64:576–579.
Patterson MB, Balough BJ: Review of pharmacological therapy for tinnitus. Int Tinnitus J 2006;12:149–160.
Puel JL, Ruel J, Guitton M, Wang J, Pujol R: The inner hair cell synaptic complex: physiology, pharmacology and new therapeutic strategies. Audiol Neurotol 2002;7:49–54.
Quaranta A, Portalatini P, Henderson D: Temporary and permanent threshold shift: an overview. Scand Audiol Suppl 1998;48:75–86.
Ruel J, Bobbin RP, Vidal D, Pujol R, Puel JL: The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea. Neuropharmacology 2000;39:1959–1973.
Ruel J, Wang J, Rebillard G, Eybalin M, Lloyd R, Pujol R, Puel JL: Physiology, pharmacology and plasticity at the inner hair cell synaptic complex. Hear Res 2007;227:19–27.
Sakata H, Kojima Y, Koyama S, Furuya N, Sakata E: Treatment of cochlear tinnitus with transtympanic infusion of 4% lidocaine into the tympanic cavity. Int Tinnitus J 2001;7:46–50.
Salt AN, Plontke S: Local inner-ear drug delivery and pharmacokinetics. Drug Discov Today 2005;10:1299–1306.
Tyler RS, Oleson J, Noble W, Coelho C, Ji H: Clinical trials for tinnitus: study populations, designs, measurement variables, and data analysis. Prog Brain Res 2007;166:499–509.
Vesterager V: Tinnitus – Investigation and management. BMJ 1997;7082:728–731.
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