Reassessment of cochlear dead regions in hearing-impaired teenagers with severe-to-profound hearing loss.

The aim of this study was to reassess cochlear dead regions after an interval of twelve months, using the Threshold Equalising Noise (TEN) test. Thirty-four ears of 24 teenagers (mean age of 14 years) with longstanding severe-to-profound sensorineural hearing impairment were tested. Testing was repeated after an interval of 12 months using the same experimental set-up. A total of eight (23.5%) out of 34 ears changed category on retest: this decreased to two (7.1%) out of 27 ears when the inconclusive category was removed from the analysis. In both of these ears (of the same participant) the criteria were met at a single frequency, and the masked threshold was only 10 dB above the TEN level per ERBN. When all of the data were examined on a frequency-by-frequency basis, the instances that changed category ranged from 15 to 51%. The range decreased to between 4 and 34% when the inconclusive category was removed from the analysis.

PSAB-OFP, a selective alpha 7 nicotinic receptor agonist, is also a potent agonist of the 5-HT3 receptor.

5-Hydroxytryptamine 3 (5-HT(3)) and alpha 7 nicotinic receptors share high sequence homology and pharmacological cross-reactivity. An assessment of the potential role of alpha 7 receptors in many neurophysiological processes, and hence their therapeutic value, requires the development of selective alpha 7 receptor agonists. We used a recently reported selective alpha 7 receptor agonist, (R)-(-)-5'Phenylspiro[1-azabicyclo[2.2.2] octane-3,2'-(3'H)furo[2,3-b]pyridine (PSAB-OFP) and confirmed its activity on human recombinant alpha 7 receptors. However, PSAB-OFP also displayed high affinity binding to 5-HT(3) receptors. To assess the functional activity of PSAB-OFP on 5-HT(3) receptors we studied recombinant human 5-HT(3) receptors expressed in Xenopus oocytes, as well as native mouse 5-HT(3) receptors expressed in N1E-115 neuroblastoma cells, using whole-cell patch clamp and Ca(2+) imaging. Our results show that PSAB-OFP is an equipotent, partial agonist of both alpha 7 and 5-HT(3) receptors. We conclude that it will be necessary to identify the determinant of this overlapping pharmacology in order to develop more selective alpha 7 receptor ligands.