THE LOOP DIURETICS

Frusemide (Frusemide, Lasix)

Based on the knowledge that frusemide reduces the endocochlear potential, it was thought that it may be suitable for the suppression of tinnitus. Although earlier trials gave promising results, the study by Jayarajan and Coles (1993) showed that, when it is administered intravenously, tinnitus was reduced in half of the subjects. However it did not appear to reduce tinnitus to a helpful degree when taken orally.
GINKGO BILOBA EXTRACTS
Ginkgo biloba is an extract from the leaves of the maidenhair tree, and is a herbal medicine with a very long history. It has been promoted for the treatment of chronic cerebral vascular insufficiency and peripheral vascular disease. It is thought to improve blood flow. It has also been used in the treatment of retinal disease and vertigo. Earlier reports on its effect on tinnitus were optimistic, however the study by Holgers et al. in 1994 did not find grounds for this optimism. The interest in its possible value for tinnitus treatment remains and a study is currently being conducted by Ewart Davies.
RECENTLY TRIED DRUGS WHICH TAKE THE PATHOPHYSIOLOGICAL MECHANISMS OF TINNITUS INTO CONSIDERATION
GAMMA AMINOBUTYRIC ACID (GABA) AGONISTS
Baclofen (Baclofen, Lioresal) 10mg tablets.

This is a selective GABA receptor drug. It is used for the treatment of trigeminal neuralgia and increased muscle tone and spasticity. L-Baclofen has been shown in animals to have suppressing effects within the cochlear nucleus (Caspary et al. 1984, Szczepaniak and Moller, 1995). Baclofen appeared to hold promise for the treatment of tinnitus. Recently Westerberg et al. (1996) made a double blind placebo controlled study on the effect of baclofen on tinnitus and found that of the 32 patients in the placebo group, 1 (3.4%) reported improvement and of the 31 subjects on baclofen 3 (9.7%) reported improvement, no significance was found. Side effects such as confusion, drowsiness, dizziness and gastrointestinal upset were related to the drug. Despite this disappointing finding, the drug may have effects on the mechanisms involved in tinnitus and further research is indicated.

PROSTAGLANDINS
Based on the knowledge that aspirin, some non-steroid anti-inflammatory drugs and aminoglycoside antibiotics have toxic effects on the cochlea with resultant hearing loss and tinnitus could partly be related to an alteration in the prostaglandin mechanism in the cochlea, Briner et al. (1993) thought it would be worth trying a synthetic prostaglandin E1 (Misoprostol) in the treatment of tinnitus. 8 of their 24 patients reported improvement during the active drug phase, together with improvement in sleep and concentration. The researchers felt that this promising result was worthy of further investigation.
DRUGS ACTING ON GLUTAMATE RECEPTORS
Caroverine

This is a drug used as a spasmolytic in some countries. It has also agonist effect on glutamate receptors in the cochlea. There is growing evidence that glutamate and glutamate receptor dysfunction is implicated in a wide range of inner ear diseases including presbycusis, noise induced hearing loss, Meniere's disease and sudden hearing loss. Denk et al. (1997) based on their earlier clinical experience, carried out a single blind study on its effect on tinnitus. Caroverine is administered only by intravenous infusion. The authors investigated the immediate effects. They found reduction in the tinnitus in 50% of the subjects. They concluded that the positive respondents had tinnitus of cochlea origin and that caroverine is probably beneficial in these cases. It is impractical to use this drug for tinnitus treatment at the moment. However it implies that in the future some drugs which can be taken orally and act on the glutamate function would be efficacious. This knowledge stimulates further research.

CONCLUSION
Although one would not discount the possibility that a drug or drugs may be found to relieve tinnitus, as yet no safe, reliable drug to cure or consistently alleviate tinnitus has been found.