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.