Effects of extracochlear gacyclidine perfusion on tinnitus in humans: a case series

Abstract

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.