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9.21) Treating Tinnitus: caroverine


This article is from the Tinnitus FAQ, by markb@cccd.edu (Mark Bixby) with numerous contributions by others.

9.21) Treating Tinnitus: caroverine

Some research on caroverine is being done in Austria:

Dr. Doris Maria DEINK c/o
Universitiftsklinik flir Hals-Nasen-Ohrenkrankheiten
Vorstand: Univ.Prof.Dr. KEhrenberger
Allgemeines Krankenhaus der Stadt Wien
1090 Wien, Wahringer Gurtel 18-20
Telephone: 011-43-1-426355

September 9, 1994

Dear Mr. Berger,

Referring to your letter of August 1994, 1 am writing to
give you some informations, about our tinnitus treatment
with Caroverine. As you already know, the treatment with
Caroverine is indicated in cases of cochlearsynaptic
tinnitus. Therefore, a thorough ENT and audiological
examination is necessary before therapy to rule out other
tinnitus causes. If necessary, the diagnostic measurements
should also comprise brainstem audiometry. As far as I know,
Caroverine is not available as a registered drug in the
United States. Therefore, I do not know any collegue who
uses this substance in tinnitus treatment. Caroverine is a
commercially available drug in Austria (Spasmium-R),
Switzerland and Japan. In Austria, Spasmium-R has been used
as a spasmolytic drug for nearly 30 years. I am enclosing
some information about Spasmium-R. Caroverine is a
Quinoxaline - derivative. It is produced by
You can get further informations about the availability of
Spasmium-R from: PHAFAG AG, Im Bretscha 29,FL-9494, SCHAAN,
LIECHTENSTEIN FAX 05/075/232 19 93.

For tinnitus treatment, Caroverine is applied as slow
intravenous infusion (2 ml per minute). The dosage of
Caroverine differs from patient to patient and depends on
the tinnitus reduction achieved in the individual patient.
When the tinnitus is reduced, the infusion is stopped. At
maximum, 160mg Caroverine (4 ampules) are given in 100ml
physiologic saline solution. Until now, we have not observed
any severe side-effects. In some patients, a slight
transient headache or dizziness occured. I hope that our
informations will help you a little.

With best wishes for you,
Yours sincerely,
Dr. Doris-Maria Denk, MD

Dr. Doris Maria Denk
Allgemaines Krankenhaus der Stadt Wien
Vorstand: Prof. Dr. K. Ehrenberger
A-1090 Wien Lazarettgasse 14
tel. 40400/3305
FAX 43/222/4021722

Jan.23, 1993

The symptom tinnitus may be due to various causes.
Therefore, an exact audiological examination is absolutely
necessary. The tinnitus therapy with transmitter antagonists
can influence a special form of tinnitus - the so called
cochlear synaptic tinnitus. It is caused by functional
disturbances in the synapse between the inner hair cells and
the afferent dendrites of the auditory nerve. By intravenous
application of transmitter antagonists (e.g. GDEE,
Caroverine) the synaptic function can be improved and the
tinnitus reduced.

All other forms of tinnitus cannot be reduced by transmitter
antagonists. The substances we use for therapy of cochlear
synaptic tinnitus are GDEE (Glutamic acid diethyl ester) and
Caroverine. GDEE is not a registered drug and is only
available upon special request by the clinic. The substance
is produced by "FLUKA Biochemie, Industriegasse 25, CH-9479
BUCHS, Switzerland). GDEE has to be lyophilised in order to
be effectful. Now we are mainly using Caroverine. This
substance is a registered drug in Austria (SpasmiumR) and
known for its spasmolytic effect. At the Annual Meeting of
the American Academy of Otolaryngology Head and Neck Surgery
in Washington in September 1992 I reported about our
results. Now we are preparing a publication. I am enclosing
some information about our therapy (including papers about
the theoretical basis).

In your case the tinnitus etiology seems to be noise. If in
addition to the mechanical damage of the inner ear a
functional disturbance is present, there is a chance to
influence the tinnitus. If you like to come to Vienna for
therapy, please contact me to fix a date. I would propose a
date at the beginning of March. If I can be of any further
assistance, please let me know.

Yours sincerely,
Doris-Maria Denk, MD.

Head and Neck Surgery
Therapy of Cochlear Synaptic Tinnitus
and K EHRENBERGER MD, Vienna, Austria

Tinnitus occurs in about 60% of inner ear diseases. A
tinnitus model that explains the pathophysiology of a
certain type of cochlear tinnitus, the so called cochlear
synaptic tinnitus, is presented. Cochlear synaptic tinnitus
is caused by functional disturbances of the synapse between
inner hair cells and afferent dendrites of the auditory
nerve. This may be the case in sudden hearing loss, hearing
loss in the elderly ("presbycusis") or noise-induced hearing
loss. The cochlear synapse has the following
characteristics: (1) glutamate is supposed to be the
transmitter substance, and (2) on the subsynaptic membrane,
two different receptor types work as a dual receptor system:
NMDA (N-methyl-D-aspartate) and non-NMDA-receptors
(Quisqualate, Kainate). This dual receptor system is
responsible for a typical pattern of depolarization, which
can be shown in microiontophoretic animal experiments. Under
pathological conditions, spontaneous receptor-dependent
depolarization patterns mimic sound-induced patterns, which
are perceived as tinnitus. On the basis of these
considerations, we use the specific Quisqualate antagonist
glutamic acid diethyl ester (GDEE) for therapy of cochlear
synaptic tinnitus to normalize the synaptic function. We
have treated 130 patients by intravenous application of
GDEE. In 77.2% of the patients, tinnitus was reduced by more
than 50% in absolute values of sound intensity. The
indications, diagnostic and therapeutic procedures, as well
as methods of subjective and objective evaluation of the
therapeutic effect, will be discussed.

Countries Where Available and Release Dates: Austria (1970);
Sp. synonyms: v TP 20 1 - I
Brand Names und Manufacturers:
Base: Espasmofibra-Faes (Spain), Spasmiurn-Donau Pharmazie
Hydrochloride: Espasmofibra-Faes (Spain), Spasmium-Donau
Pharmazie (Austria)
Drug Action: Spasmolytic.
Indications/Usage: Intestinal spasm; biliary spasm.
How Supplied: 20 mg capsules; 40 mg ampules; 40 mg
Dosage: 40 mg up to 3 times daily.
Precautions/Warnings: Hyperthyroidism; cardiac
insufficiency; muscular weakness in the elderly and
Contraindications: Glaucoma; prostate hypertrophy; duodenal
Interactions: Phenothiazines; anticholinergics;
antihistamines; tricyclic antidepressants; digoxin.
Adverse Effects: Dry mouth; blurred vision; urinary
retention; tachycardia.
US Treatments: Cicyclomine, L-hyoscyamine and propanthelin
are US anticholinergic drugs with similar pharmocologic


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