The
Promise of Caroverine for Tinnitus
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”
(http://www.tinnitusformula.com/info/articles/treat/inner_ear_meds.asp).
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
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