Gacyclidine (OTO311) is a small molecule N-methyl-D-aspartate (NMDA) receptor antagonist. Local injection of Gacyclidine in the cochlea inhibits salicylate-induced tinnitus and can be used to treat brain injury, spinal cord injury and tinnitus.

In primary cortical cultures, gacyclidine and its enantiomers, at 0.1 to 5.0 μM, prevent glutamate-induced neuronal death.[1]

In rats, the in vivo neurotoxicity of gacyclidine is far lower than that of MK-801. No necrotic neurons were detected in animals sacrificed at 18 or 96 h after treatment with gacyclidine (1, 5, 10, or 20 mg/kg i.v.). At the highest (20 mg/kg) but not the lower doses (1-100 mg/kg) electron microscopy revealed the presence of few cytoplasmic or intramitochondrial vacuoles. Moreover, in rats, gacyclidine exerts a dose- and time-dependent neuroprotection in three models of spinal cord lesions. Beneficial effects of gacyclidine include reduction of lesion size and improvement of functional parameters after injury. In traumatic brain injury models, gacyclidine improves behavioral parameters and neuronal survival. Optimal protection is obtained when gacyclidine is administered at 0 to 30 min after injury.[1]