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    Science. 2003 Jul 11;301(5630):226-9.

    5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia.

    Manzke T, Guenther U, Ponimaskin EG, Haller M, Dutschmann M, Schwarzacher S, Richter DW.

    Department of Neuro- and Sensory Physiology, University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany.

    Comment in:

    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 PBC neurons 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.

    PMID: 12855812 [PubMed - indexed for MEDLINE]

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