By Barry Keate
The delicate hair cells of the cochlea are the synapse, or transfer point responsible for transforming sound waves into electrical signals that are sent to the brain and interpreted as sound. Most forms of tinnitus are described as cochlear synaptic tinnitus. This is a condition where the inner hair cells have been damaged by causes such as noise exposure, ototoxic drugs or Meniere’s disease.
When these inner hair cells are functionally damaged, there is an excess production of glutamate and the glutamate receptors in the cochlea become overexcited with a toxic dose of glutamate. This is a condition called excitotoxicity of the glutamate receptors.
It is now generally agreed by medical researches that glutamate is the major excitatory neurotransmitter in the brain and that over production of glutamate has toxic effects that lead to cell death in the receptors. Chronic malfunctioning of glutamate systems in the brain may be involved in many neurodegenerative diseases such as Huntington’s, Parkinson’s and Alzheimer’s diseases. Researchers are studying neuroprotective agents as a treatment for these conditions. The same condition in the cochlea can lead to hearing loss and tinnitus.
One such neuroprotective agent being studied for tinnitus is the glutamate antagonist Caroverine, which has been used in Austria for almost 40 years, under the trade name Spasmium-R, as an oral anti-spasmodic medication. Caroverine is not available in the US or Canada for any purpose as it has not been approved by the FDA. It is currently available only in Austria, Switzerland and Japan.
Professor Klaus Ehrenberger at the University of Vienna, Otolaryngology Clinic, has been investigating the effects of Caroverine on tinnitus patients for several years. He initially began using an IV infusion on patients and had remarkable success. In one study, conducted in 1997, Caroverine reduced tinnitus symptoms for most patients 1. 63% of patients responded immediately with a significant reduction in sound levels. There were no significant side effects and mild side effects were transitory, typically disappearing in less than 24 hours.
Caroverine cannot be taken by IV infusion over a long period of time. It has to be administered in high doses to overcome the blood-labyrinth barrier and penetrate the cochlea. Glutamate is very important to many bodily functions and must not be inhibited long-term. Glutamate is an amino acid and one of the most important building blocks of proteins. It is also vital for metabolism and brain function. It was necessary to come up with a better way to deliver it directly to the cochlea.
Drs. Ruan, Soh and Yeoh in Singapore investigated delivering Caroverine directly into the inner ear using a transtympanic micro-catheter 2. Readers of our newsletter may remember that this procedure for delivering medication directly to the inner ear was described by tinnitus authority Dr. Michael Seidman in his article “Medicines to Treat Inner Ear Disorders”
Essentially, a micro-catheter is threaded around the eardrum and attached to the Round Window Membrane (RWM), the barrier that separates the cochlea from the rest of the body. Medicines are fed into the catheter and allowed to stand on the RWM, gently perfusing through it. This method keeps the medication from entering the entire system and concentrates it in the cochlea.
This treatment method is superior to IV infusion but still has some drawbacks. Inserting a micro-catheter is invasive and painful. Also, it cannot be used over a long period of time. The catheter has to be withdrawn at a maximum of 23 days to prevent the possibility of infection. Caroverine treatment requires a periodic maintenance dose and this cannot be accomplished using a catheter except in the most extreme conditions.
Dr. Ehrenberger is now at work on new clinical trials using gauze soaked in Caroverine and inserted into the outer ear. He believes this method will be the least invasive, least expensive and most effective method for long-term tinnitus control. The doctor inserts the Caroverine soaked gauze into the patient’s ear who later adds an additional 2 drops of Caroverine that evening. The next morning the patient returns to the clinic where the gauze is changed and the treatment continues for 4 days. If the patient does not respond within that time period, it is considered to be unhelpful for the patient.
Dr. Ehrenberger has not published findings on this treatment therapy as trials are now underway. Caroverine has also reported to be very helpful in reducing or eliminating Meniere’s symptoms.
It may be possible in the future to use ear drops for the reduction of tinnitus. This would be a low cost, home applied treatment. It will probably be a year or more before Dr. Ehrenberger’s findings are published. At that point, trials could possibly begin in the US. After the trials are concluded, and depending on results, applications will be made to the FDA and the approval process will begin.
In the meantime, it is very important to know that premium-grade Ginkgo Biloba Extract (GBE) provides many of the same neuroprotective effects GBE has protective effects against glutamate induced neuronal damage 3. Premium-grade GBE is one of the primary ingredients in Arches Tinnitus Relief Formula™.
The struggle against the agony of tinnitus is slowly being won. Caroverine may be one more arrow in the quiver of therapies that will eventually lead to the control of tinnitus.
Please note: Arches has no contact information for Dr. Ehrenberger nor do we have more information than that presented above. If you are interested in pursuing this treatment, please contact the Otolaryngology Clinic at the University of Vienna, Austria.
- Acta Otolaryngol. 1997 Nov;117(6):825-30
- Singapore Med J 1999; Vol 40(01)
- Acta Pharmacol Sin 1997 JUL;18(4):344