Despite considerable progress i our understanding of olfactory dysfunctions, there is still relatively little known about the causes of taste disorders. Medication usage, however, appears to be one of the most common etiologic factors contributing to disturbances in oral sensory perception. The proposed studies seek to elucidate both the nature and bases of taste aberrations associated with carbonic anhydrase inhibitors (CAIs). Through both acute studies with normal volunteers and a study of glaucoma patients receiving chronic CAI therapy, we will characterize psychophysically the nature of changes in oral sensory perception produced by CAIs. Acute studies will provide the experimental control necessary for detailed examination of the time course of these changes, as well as for parallel assessment of changes in salivary flow and buffering capacity that may be produced by CAIs and contribute to taste changes; a study of the acute effects of CAIs on salivary carbonic anhydrase activity is also proposed. The patients study will allow determination of the incidence and clinical implications of altered oral sensory perception secondary to CAI therapy. Finally, animal model studies are proposed to elucidate the neural mechanisms underlying the taste effects of CAIs. In addition to providing an understanding of taste alterations associated with carbonic anhydrase inhibition, the proposed studies should add to basic knowledge of factors contributing to gustatory transduction. More generally, they will shed light on the phenomenon of drug-induced alterations in taste by providing information regarding the specific types of changes that may occur, potential peripheral mechanisms for these changes, and their clinical implications.
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