University of Pittsburgh researchers have designed and synthesized novel carbamates to target the potassium channels (K-channels) in auditory synapses, a novel target for the treatment of tinnitus. Additionally, K channels have been identified that may be a novel therapeutic target to treat epilepsy.
Description
Following the identification of the role of K-channels, compounds have been developed to improve KCNQ2/3 channel activity in a potent, specific, yet less toxic mode than previously existing KCNQ channels. K-channels play a critical role in the development of tinnitus by reducing membrane response time and shortening the duration of excitatory postsynaptic potentials (EPSPs) and APs. A decrease in KCNQ2/3 channel activity leads to hyperexcitable auditory brainstem circuits, which in turn promotes tinnitus and epilepsy. Targeting these K-channels with carbamates is a promising approach for the treatment of these conditions.
Applications
1. Treatment and prevention of tinnitus.
2. Treatment of epilepsy.
Advantages
Tinnitus is a common auditory disorder that typically begins after extreme sound exposure. An estimated 5 to 15 percent of the population experiences chronic tinnitus, and many millions of those sufferers, including veterans, often become disabled. While, for some, tinnitus may ease with time, for many it continues to be a challenge to treat and remains a global unmet need.
This approach offers promising treatment by directly targeting K-channels linked to tinnitus, providing novel treatment options that are more potent, specific, and less toxic than the existing KCNQ channels. Additionally, this approach could be applied as a treatment for epilepsy, due to the involvement of K-channels in this condition.
Invention Readiness
Small scale animal studies have shown these compounds are promising drug candidates for hte treatment of tinnitus with research in humans still required. Novel 2-amino-4-arylamino phenyl carbamates have been synthesized. Murine studies have demonstrated that treatment with these carbamates following noise exposure reduced the number of animals experiencing signs of tinnitus.
IP Status
https://patents.google.com/patent/US10526280B2
