There goes my spelling again.

I am really interested.

By the end of this year, I am going to put my t to rest, one way or the other.

Europe/Micro Transponder, or India, or to hell and back.

I know something is going to pop up.

Description
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
DONAU-PHARMAZIE-CEHASOL Ges.m.b.H., A-1230 VIENNA, AUSTRIA.
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
HALS-, NASEN- UND OHRENKLINIK
DER UNIVERSITAT 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
DORIS MARIA DENK MD (presenters, R. BRIX PHD, D. FELIX PHD,
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.

CAROVERINE
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
(Austria)
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
suppositories
Dosage: 40 mg up to 3 times daily.
Precautions/Warnings: Hyperthyroidism; cardiac
insufficiency; muscular weakness in the elderly and
disabled.
Contraindications: Glaucoma; prostate hypertrophy; duodenal
obstruction.
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
properties





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next: 9.22) Treating Tinnitus: carbogen


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Read more: http://stason.org/TULARC/health/body/tinnitus-ringing-ears/9-21-Treating-Tinnitus-caroverine.html#ixzz1xbGzHdsA

I lost track of what was happening with it. I think it was legalized in India as a T treatment but I've never seen any real reports of it working.

Ok, does ANYBODY know ANYBODY who tried it on this forum or any other forum???????????????????

Here are the results of a clinical trial

Acta Otolaryngol. 1997 Nov;117(6):825-30.
Caroverine in tinnitus treatment. A placebo-controlled blind study.
Denk DM, Heinzl H, Franz P, Ehrenberger K.
SourceENT Department, University of Vienna, Austria.

Abstract
This study was performed to examine whether a single infusion of caroverine, a quinoxaline-derivative, can be used successfully in the treatment of inner ear tinnitus. Microiontophoretical experiments in guinea-pigs have shown that caroverine acted as a potent competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazone-proprionic acid (AMPA) receptor antagonist and, in higher dosages, a non-competitive N-methyl-d-aspartate (NMDA) antagonist. According to our working hypothesis of the pathophysiology of inner ear tinnitus (cochlear-synaptic tinnitus), these forms of tinnitus occur when the physiological activity of the NMDA and AMPA receptors at the subsynaptic membranes of inner hair cell afferents is disturbed. In total, 60 patients with inner ear tinnitus of assumed cochlear-synaptic pathophysiology were included in the study: after computerized randomization, 30 were treated with caroverine and 30 with placebo. For a response to have occurred, tinnitus had to show a reduction in both subjective rating and psychoacoustic measurement (tinnitus matching). In the caroverine group, 63.3% responded to therapy immediately after the infusion. In the placebo group, none of the patients treated showed a significant response according to the defined success criteria. The results confirm our working hypothesis on the genesis of cochlear-synaptic tinnitus.

Comment in
Acta Otolaryngol. 1998 Jul;118(4):606-8.
PMID:9442821[PubMed - indexed for MEDLINE] Publication Types, MeSH Terms

They are on phase 3 of clinical trials in Austria
it was suspended on a temp bases.

History of this study Current version of this study
View of NCT01174979 on 2011_11_18
ClinicalTrials Identifier: NCT01174979
Updated: 2011_11_18
Descriptive Information
Brief title Caroverin and Inner Ear Diseases

Official title Double Blind, Placebo-controlled, Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Transtympanic Treatment of Tinnitus With Caroverine

Brief summary
This trial is a randomized, double blind, placebo controlled study on patients suffering from inner ear diseases with tinnitus as a principal symptom.
The study will investigate the transtympanic treatment with a 1,5 % caroverine solution.
Each patient will undergo treatment for 2 cycles of 48 hours each.

Detailed description


Phase Phase 3
Study type Interventional
Study design Treatment
Study design Randomized
Study design Double Blind (Subject, Investigator)
Study design Parallel Assignment
Study design Safety/Efficacy Study
Primary outcome Measure: to investigate the efficacy of Caroverin in transtympanic treatment of patients with tinnitus measured by a visual analogue scale.
Time Frame: treatment takes 5 days, follow up examination 4 weeks after
Safety Issue? No
Secondary outcome Measure: to investigate the time from the start of treatment to an improvement in tinnitus
Time Frame: treatment takes 5 days, follow up examination 4 weeks after
Safety Issue? No
Secondary outcome Measure: to investigate the efficacy of Caroverin depending the origin of tinnitus
Time Frame: treatment takes 5 days, follow up examination 4 weeks after
Safety Issue? No
Secondary outcome Measure: to investigate the safety of Caroverin treatment
Time Frame: treatment takes 5 days, follow up examination 4 weeks after
Safety Issue? Yes
Secondary outcome Measure: to investigate the impact of Caroverin treatment of quality of life
Time Frame: treatment takes 5 days, follow up examination 4 weeks after
Safety Issue? Yes
Condition Tinnitus
Arm/Group Arm Label: Caroverin Experimental

Arm/Group Arm Label: Placebo Placebo Comparator

Intervention Drug: Caroverin Arm Label: Caroverin
treatment with eardrops 2 times for 48 hours

Recruitment Information
Status Suspended
Start date 2011-01
Primary completion date 2012-01 (Anticipated)
Criteria
Inclusion Criteria:
Men or women aged at least eighteen
Written consent to take part in the study after receiving information from the trial physician
One of the following illnesses:
- Decompensated tinnitus
- Sudden hearing loss
- Morbus Menire
- Blast injury
- Presbyacusis with Tinnitus
- Chron. Otitis media

Exclusion Criteria:
Patients who are not able to give their consent (e.g. dementia, coma, mental disability,)
Women of childbearing age who are not using adequate contraception or who are (or plan to become) pregnant (a pregnancy test must be carried out by a doctor once a month in Austria) or are lactating
If there are solid reasons to doubt that the patient would be willing and able to cooperate
Known intolerance of/hypersensitivity to caroverine
Subjects who have taken part in another clinical trial within the 30 days preceding the start of this study or during this study
Pulse-synchronous tinnitus
Tinnitus caused by malposition of the jaw bone (bruxism)
Eardrum perforation
Subjects who have previously had a barotraumas, diving accidents or decompression sickness
Retrocochlear hearing disorder
Patients who have previously had a fracture of the petrous bone
Subjects suffering from acute or chronic accompanying conditions which severely impede their general health (NYHA stage IV, cancer, HIV etc.)
Accompanying conditions that according to the current state of scientific knowledge could affect the parameters used in this study to such an extent as to make it impossible to perform an objective assessment of those parameters, particularly ear conditions, including any conditions affecting the other ear or conditions like HI NYHA stage IV, cancer, HIV, Wallenberg Syndrome, massive Hypotension, Glaucoma.)
Accompanying medication that according to the current state of scientific knowledge are likely to affect the measurement techniques used in this study or the results obtained (cytostatics, aminoglycoside antibiotics, loop diuretics (furosemide, etacrynic acid), psycho pharmaceuticals, muscle relaxants, benzodiazepines, salicylates, quinine, cortisone and/or caroverine within the three days preceding the start of the study)
Drug treatment for tinnitus or sudden hearing loss (i.v. and oral) within seven days preceding the start of the study where the total duration of the course is less than four weeks
Diseases or conditions that may be associated with an altered perception or processing of stimuli, e.g. mental illness

Gender Both
Minimum age 18 Years
Healthy volunteers No
Administrative Data
Organization name Phafag AG
Organization study ID 1-09
Secondary ID 2009-018046-38 (EudraCT Number)
Sponsor Phafag AG
Health Authority Austria: Bundesamt fr Sicherheit im Gesundheitswesen
Health Authority Austria: Ethics Commitee Vorarlberg

Caroverine TreatmentThe 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 Menieres 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 Huntingtons, Parkinsons and Alzheimers 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 patients 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 Menieres 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. Ehrenbergers 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

"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."

That would be amazing!! : )

OH MY IF ONLY!!!
How do you know if you have cochlear synoptic tinnitus?
When was the Barry Keate's article written?
Sue