piperidines and Tinnitus

Tinnitus is a common symptom that demonstrates a significant comorbidity with anxiety and depression. The novel neurokinin-1 receptor antagonist, vestipitant, has anxiolytic properties and a good safety profile. Vestipitant was investigated for potential effect against chronic tinnitus as a stand-alone treatment and in conjunction with a selective serotonin reuptake inhibitor, paroxetine.. Randomized, double-blind, crossover study.. Tertiary neurotologic and audiologic center with additional referrals from a secondary university hospital center.. Twenty-four adult patients with tinnitus were randomized into the study.. Visual analogue scale (VAS) measurements of tinnitus loudness (intensity), pitch and distress, VAS measurements of arousal/anxiety, Tinnitus Handicap Inventory, Quick Inventory of Depressive Symptomatology, and plasma concentrations of trial drugs.. No statistically significant treatment benefit effect was detected for tinnitus (intensity, pitch, and distress) VAS scores, arousal-anxiety VAS scores, Tinnitus Handicap Inventory, or tinnitus aggravation scores assessed on Days 1 and 14. However, a statistically significant worsening of tinnitus intensity and distress scores was observed after vestipitant compared with placebo for the mean data collected over the treatment period. No relevant differences in vestipitant plasma concentrations were observed between the subjects given the combination with paroxetine and those receiving vestipitant alone. No specific relationships were observed between tinnitus intensity and vestipitant plasma concentrations.. Although well-tolerated vestipitant, alone or in combination with paroxetine, was not effective in ameliorating tinnitus in this patient group.

Topics: Cross-Over Studies; Double-Blind Method; Drug Therapy, Combination; Female; Fluorobenzenes; Humans; Male; Middle Aged; Neurokinin-1 Receptor Antagonists; Paroxetine; Piperidines; Selective Serotonin Reuptake Inhibitors; Tinnitus; Treatment Outcome

Gacyclidine, a non-competitive NMDA receptor antagonist, is a phencyclidine derivative with neuroprotective properties. It has been previously safely administered intravenously to acute traumatic brain-injured patients. Experiments in guinea pigs have shown that local administration of gacyclidine to the cochlea can suppress salicylate-induced tinnitus. Thus, we thought that patients with therapy-resistant sensorineural tinnitus might benefit from a local therapy with gacyclidine. As a compassionate treatment, we administered aqueous gacyclidine solution via a Durect RWmuCath(TM) into the round window niche in six patients with unilateral deafness associated with tinnitus. The response of each patient to the drug treatment was given a numerical value by the use of a visual analogue scale (VAS) on a scale of 0-10 for tinnitus intensity, where 0 represented no tinnitus and 10 represented unbearable tinnitus-intensity or -annoyance (subjective). After constant perfusion of gacyclidine for 40-63 h, four out of six patients experienced a temporary relief from their tinnitus. No serious side effects were recorded in any of the cases. Gacyclidine might present a potent drug for the suppression of sensorineural tinnitus in humans and therefore should be considered for future double-blinded, placebo-controlled clinical trials. For lasting effective treatment, controlled intracochlear and long-term delivery of the drug seems to be necessary. Further studies investigating the toxicological effects of gacyclidine intracochlear perfusion as well as different dosages and therapy durations are under way to ensure the safety of the drug for long-term human use and warrant clinical trials.

Topics: Administration, Topical; Adolescent; Adult; Audiometry, Pure-Tone; Cochlea; Cyclohexenes; Female; Hearing Loss, Sensorineural; Humans; Male; Middle Aged; Neuroprotective Agents; Piperidines; Receptors, N-Methyl-D-Aspartate; Round Window, Ear; Tinnitus; Young Adult

Tinnitus, the perception of sound in the absence of external acoustic stimulation, is a common and devastating pathology. It is often a consequence of acoustic trauma or drug toxicity. The neuronal mechanisms of tinnitus are neither yet fully understood nor are effective treatments available. Using a novel behavioral paradigm for measuring tinnitus in the rat based on tone-guided navigation, we show here that the development of long-term noise-induced tinnitus, the most prevalent and clinically important form of human tinnitus, can be abated by local administration of the NMDA antagonist "ifenprodil" into the cochlea in the first 4 days following the noise insult but not afterwards. This suggests that long-term tinnitus undergoes a consolidation-like process, resembling the ontogeny of items in long-term memory. Furthermore, this finding paves the way to potential therapeutic strategies for the prevention of chronic tinnitus once the noise insult had taken place.

Topics: Acoustic Stimulation; Animals; Audiometry; Chronic Disease; Cochlea; Excitatory Amino Acid Antagonists; Hair Cells, Auditory; Hearing; Male; Neuronal Plasticity; Piperidines; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Time Factors; Tinnitus; Treatment Outcome

Topics: Administration, Oral; Adrenergic alpha-Antagonists; Adult; Age Factors; Amino Alcohols; Craniocerebral Trauma; Deafness; Electrooculography; Humans; Injections, Intravenous; Ischemic Attack, Transient; Piperidines; Prognosis; Tinnitus; Vertigo; Vestibular Function Tests