The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression.

BACKGROUND: On the basis of experiments in rats, serotonin 4 receptor (5-hydroxytryptamine 4 [ 5-HT4]) agonists have been proposed as a novel therapeutic strategy for the selective treatment of respiratory depression caused by opioids while leaving analgesic effects unaffected. The effects in rats have been seen with the 5-hydroxytryptamine 4a (5-HT4a) agonist BIMU8, which is currently not available for use in humans. METHODS: In a proof-of-applicability study, the clinically recommended dose of 5 mg mosapride, currently the only 5-HT4 agonist available for clinical use, was given in a placebo-controlled manner 3 times daily for 5 days to 12 healthy men and women. During the actual experiments, a further 15 mg mosapride was administered. After baseline measurements of respiratory depression, by use of a carbon dioxide rebreathing method, and of pain, by use of electrical and chemical pain stimuli, 30 mg morphine per 70 kg body weight was administered intravenously within 2 hours. After assessment of respiratory depression and pain, 2 mg naloxone was intravenously administered within 20 minutes, followed by a third assessment of respiratory depression and pain. In ancillary experiments 10 rats received 100 mg/kg mosapride orally or placebo 50 minutes before intraperitoneal injection of 10 mg/kg morphine, followed 20 minutes later by injection of naloxone, and the respiratory frequency was monitored. RESULTS: With placebo coadministration, the slope of the relationship between expiratory volume and CO2 concentration in the inspired air was significantly reduced, from 1.11 +/- 0.46 L/mm Hg CO2 at baseline to 0.39 +/- 0.25 L/mm Hg CO2 at the end of the morphine infusion (P < .001). Coadministration of mosapride had no effect on respiratory depression induced by morphine (slope of 0.39 +/- 0.19 L/mm Hg CO2, P > .7). In contrast, naloxone significantly reversed the slope to 0.78 +/- 0.36 L/mm Hg CO2 (P = .001). Morphine produced significant effects on electrical and chemical pain stimuli, which were partially reversed by naloxone, but mosapride did not affect the analgesic effects of morphine. In rats mosapride similarly failed to prevent a slowing of the breathing frequency after morphine administration but naloxone reversed the respiratory depression. CONCLUSION: Our results show that, with mosapride, opioid-induced respiratory depression cannot be prevented, and because other 5-HT4 agonists are not currently available for clinical use, a cure for opioid-induced respiratory depression as promised by the previous successful experiments in laboratory animals is not yet available in clinical practice.[1]


  1. The 5-hydroxytryptamine 4 receptor agonist mosapride does not antagonize morphine-induced respiratory depression. Lötsch, J., Skarke, C., Schneider, A., Hummel, T., Geisslinger, G. Clin. Pharmacol. Ther. (2005) [Pubmed]
WikiGenes - Universities