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5-HT4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia

Science  11 Jul 2003:
Vol. 301, Issue 5630, pp. 226-229
DOI: 10.1126/science.1084674

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Abstract

Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBCneurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor–specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3′,5′-monophosphate levels through the convergent signaling pathways in neurons.

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