Biomedical subjects

Klaus Ehrenberger

Publications and source records attributed to Klaus Ehrenberger.

7 recordsLinked to original sources

PubMed2005

Topical administration of Caroverine in somatic tinnitus treatment: proof-of-concept study.

This prospective study, which conformed with good clinical practice (GCP-conform), tested the concept that the topical transtympanic administration of the quinoxaline derivative Caroverine promises a new approach to the treatment of tinnitus. The rationale for the study is the hypothesis that tinnitus reflects sequelae of auditory neurotoxicity that can prevented and repaired by the neuroprotective and neuroregenerative activities of quinoxaline derivatives exhibited in previous preclinical tests. In a representative patient cohort, the probability of a long-lasting tinnitolytic effect of lipophilic eardrops containing 1% Caroverine as their active ingredient gained in significance, crossing from low-intensity levels to high-intensity levels of individual tinnitus sensations. These results encouraged us to design consequential GCP-conform phase 2 and phase 3 studies.

Administration, Topical↗

PubMed2003

The antioxidant activity of caroverine.

Caroverine, 1-(2-diethylaminoethyl)-3-(p-methoxy benzyl)-1,2-dihydro-2-quinoxalin-2-on-hydrochloride, is a class B calcium-channel-blocker and antiglutamatergic agent with significant effects on the brain function. Caroverine exhibits competitive AMPA antagonism, and at higher concentrations, noncompetitive NMDA antagonism. In clinical practice caroverine is used as a spasmolytic and otoneuroprotective agent. Since reactive oxygen species are supposed to be involved in the pathogenesis of inner ear diseases in which caroverine shows beneficial effects, the present study aimed to investigate the antioxidant properties of caroverine. Lipid peroxidation of liposomal membranes was suppressed in the presence of caroverine. In order to understand the mechanism of this antioxidant action of caroverine, we determined the rate constants both for a possible reaction with superoxide (O(2)(.-)) radicals from xanthine/xanthine oxidase and for a possible reaction with hydroxyl (.OH) radicals in Fenton system. Using a defined chemical reaction model O(2)(.-) scavenging was found to occur at a rather low rate constant only (3 x 10(2)M(-1)s(-1)). Thus, a reaction of caroverine with O(2)(.-) radicals is of marginal significance. In contrast, the reaction of caroverine with .OH radicals occurs at an extremely high rate constant (k=1.9 x 10(10)M(-1)s(-1)). The strong antioxidant activity of caroverine is therefore based both on the partial prevention and highly active scavenging of hydroxyl radicals.

Analysis of Variance↗

PubMed2003

Do middle ear muscles trigger attacks of Menière's disease?

OBJECTIVE: Current surgical methods for treating Ménière's disease (MD), e.g. endolymphatic sac surgery, mastoidectomy or insertion of middle ear ventilation tubes, only improve vertigo and fail to influence the hearing threshold. In this retrospective study we examined the long-term effects of tenotomy on the symptoms of MD. MATERIAL AND METHODS: A total of 45 patients suffering from definite MD underwent middle ear muscle tenotomy, a treatment that is very rarely considered nowadays. Of these 45 patients, 20 were observed postoperatively for a period of > 2 years. The disease was scored pre- and postoperatively and the results were evaluated according to the American Academy of Otolaryngology-Head and Neck Surgery Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of therapy for MD. RESULTS: Sectioning of the tensor tympani and stapedius muscle tendons significantly reduced the frequency and intensity of vertigo and improved both the functional profile and tinnitus. Pure-tone audiometry at frequencies between 500 and 3000 Hz substantiated the improvement in hearing threshold, as did the pure-tone average. The therapeutical outcome was stable in cases where both tendons remained persistently disconnected. Intratympanal inflammatory reactions were observed in most patients during surgery. CONCLUSION: Our results prove that tenotomy is a successful and enduring therapeutic approach for treating the auditory and vestibular symptoms of MD and strongly suggest that it should be reconsidered as a promising surgical treatment for the symptoms of MD.

Adult↗

PubMed2002

Different action of memantine and caroverine on glutamatergic transmission in the mammalian cochlea.

Glutamate is the major transmitter candidate between inner hair cells and the afferent neurons of the mammalian cochlea. We investigated the action of memantine (1-amino-3,5-dimethyl-adamantane) and the quinoxaline derivative caroverine [1-diethylaminoethyl-3,8-(p-methoxybenzyl)-1,2-dihydro-quinoxaline-dione] on the glutamatergic transmission in the guinea pig cochlea utilizing extracellular recording techniques and microiontophoretic ejection of substances. While memantine was able to inhibit the NMDA (N-methyl-D-aspartate)-induced firing, the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-stimulated activity was unaffected. In contrast, caroverine could block both NMDA- as well as AMPA-induced firing. As memantine and caroverine are currently in clinical use, these substances could be introduced to the treatment of several cochlear disorders.

Animals↗

PubMed2002

Clinical experience with caroverine in inner ear diseases.

The glutamatergic synapses between the cochlear inner hair cells and their afferent neurons seem to be mostly involved in the pathophysiology of the cochlea. Glutamatergic neurotoxicity is characterized by a mitochondrial overproduction of free oxygen radicals damaging lipid membranes and DNA structures of the postsynaptic neuron followed by the clinical symptoms of hearing loss and tinnitus. In preclinical tests, quinoxaline derivatives antagonized these deleterious consequences of too high an amount of free radicals. Therefore the clinically available quinoxaline dione caroverine provides a new approach to a successful treatment of tinnitus, sudden hearing loss and speech discrimination disorders in presbyacusis. The results of corresponding clinical trials are presented.

Cochlea↗

PubMed2002

The quinoxaline derivative caroverine in the treatment of sensorineural smell disorders: a proof-of-concept study.

The treatment of non-conductive olfactory disorders is to a large extent an unsolved problem. This proof-of-concept study focused on possible effects of the N-methyl-D-aspartate (NMDA) antagonist caroverine. Potential mechanisms for the hypothesized effect included reduced feedback inhibition in the olfactory bulb as a consequence of NMDA antagonistic actions and antagonism of an excitotoxic action of glutamate. A total of 77 consecutive patients with non-conductive olfactory disorders were included in the study. Fifty-one patients received caroverine for 4 weeks (120 mg/day); 26 controls matched for age, gender and duration of olfactory loss were treated with zinc sulfate for the same length of time (400 mg/day). Olfactory sensitivity was evaluated before and after treatment. Testing included assessment of n-butanol odor threshold and odor identification. When compared to baseline, treatment with caroverine improved both odor thresholds (p = 0.005) and odor identification (p = 0.042) in anosmic patients. In hyposmic patients it significantly improved odor identification ability (p = 0.041). In contrast, zinc sulfate had no significant effect on olfactory function. These results indicate that caroverine appears to be effective for the treatment of non-conductive smell disorders.

Adolescent↗

PubMedDate not supplied

Change of complexity patterns in human posture during aging.

Human posture is a prototypical example of a complex control system. The joint output of several physiological - most likely nonlinearly interacting - processes leads to correctional movements which enable us to stand upright. These correctional body movements reflect some features of the underlying control mechanisms. We analyze the movements of quietly standing persons by means of various types of fractal measures, which are designed to capture 'degrees of complexity'. We observe changes of these fractal measures as a function of age and show that aging goes hand in hand with a decrease of complexity in movement patterns towards more regular movements. We try to explain these results in a stochastic resonance framework. We conjecture that the reduction of posture complexity is linked to deteriorated balance performance and argue that clinical treatment of age-related balance problems should focus on regaining this complexity therapeutically. We line out two possible starting points for actual therapy.

Adult↗