Can caroverine be used for tinnitus treatment?

Fråga: Can caroverine be used for tinnitus treatment?

Sammanfattning: On the basis of its antiglutamatergic properties and of its low profile of side-effects, caroverine seems to be a promising drug for the therapy of some forms of tinnitus. Nevertheless, before starting with such therapy, a thorough audiological and neurological examination is necessary to rule out other tinnitus causes.

Svar: Caroverine is a well known smooth muscle relaxant, used in many countries for its spasmolytic properties in condition associated with painful smooth muscle spasm (1). The drug may also exert central effects due to its calcium channel blocking action and glutamate antagonism (1).

In the mammalian cochlea neurotransmission between inner hair cells and afferent auditory neurones is probably mediated by glutamate (2), and neurotoxicity induced by excessive glutamate release seems to play a crucial role in some pathological condition of the cochlea (3,4). Therefore glutamate antagonists have been evaluated (5) as a new therapeutic strategy for different inner ear diseases, such as sudden hearing loss, noise trauma, presbyacutis and tinnitus.

Tinnitus occurs in about 60 per cent of inner ear diseases. This symptom may be due to various causes. A special form of tinnitus, the so-called cochlear synaptic tinnitus, is caused by functional disturbances in the synapse between the inner hair cells and the afferent dendrites of the auditory nerve (5). Under pathological conditions, spontaneous receptor-dependent depolarisation patterns mimic sound induced patterns, which are perceived as tinnitus. Glutamate is supposed to be the transmitter substance involved in these pathological events. On the basis of these considerations, caroverine has been evaluated in different studies (4-7) for the therapy of cochlear synaptic tinnitus, to normalize the synaptic function. In most of those clinical trials, caroverine exhibited a statistically significant otoneuroprotective action in noise-induced hearing loss and tinnitus. The drug has also been shown to have a low potential for side effects (6). Besides, local application to the cochlea could be the best way to administer glutamate antagonist in sufficient amounts while avoiding systemic side-effects (5).

Caroverine has also been shown (8,9) to have a potential of acute cerebro-protective effects in hypoxia due to both its calcium channel blocker and antiglutamatergic properties. 1 Reynolds JEF, editor. Martindale, The extra pharmacopoeia. 31st ed. London: Royal Pharmaceutical Society; 1996. p. 1686 2 Eybalin M: Neurotransmitters and neuromodulators of the mammalian cochlea. Physiol Rev 1993; 73: 309-373 3 Pujol R, Puel JL, Gervais d´Aldin C, Eybalin M: Pathophysiology of the glutamatergic synapses in the cochlea. Acta Otolaryngol (Stockh) 1993; 113: 330-334 4 Ehrenberger K, Felix D: Receptor pharmacological models for inner ear therapies with emphasis on glutamate receptors: a survey. Acta Otolaryngol (Stockh) 1995; 115: 236-240 5 Oestreicher E, Arnold W, Ehrenberger Km Felix D: New approaches for inner ear therapy with glutamate antagonists. Acta Otolaryngol (Stockh) 1999; 199: 174-178 6 Denk DM, Heinzl H, Franz P, Ehrenberger K: Caroverine in tinnitus treatment. A placebo-controlled blind study. Acta Otolaryngol (Stockh) 1997; 117: 825-830 7 Domeisen H, Hotz MA, Häusler R: Caroverine in tinnitus treatment. Acta Otolaryngol (Stockh) 1998; 118: 606-607 8 Saletu B, Grunberger J, Anderer P, Linzmayer L, König P: On the cerebro-protective effects of caroverine, a calcium-channel blocker and antiglutamatergic drug: double-blind, placebo-controlled, EEG mapping and psychometric studies under hypoxia. Br J Clin Pharmacol 1996; 41: 89-99 9 Saletu B, Grunberger J, Anderer P, Linzmayer L, Konig P: Acute central effects of the calcium channel blocker and antiglutamatergic drug caroverine. Double-blind, placebo-controlled, EEG mapping and psychometric studies after intravenous and oral administration. Arzneimittelforschung 1995; 45: 217-229