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

  title={5-HT4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia},
  author={Till Manzke and Ulf Guenther and Evgeni G. Ponimaskin and Miriam Haller and Mathias Dutschmann and Stephan W. Schwarzacher and Diethelm W. Richter},
  pages={226 - 229}
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… 

5-HT1A Receptor Agonist Befiradol Reduces Fentanyl-induced Respiratory Depression, Analgesia, and Sedation in Rats

The reversal of opioid-induced respiratory depression and sedation by befiradol in adult rats was robust, whereas involved mechanisms are unclear, however, there were adverse concomitant decreases in fentanyl-induced analgesia and altered baseline ventilation, nociception, and behavior.

Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats.

The main beneficial effect of 8-OH-DPAT was on the pulmonary circulation; it improved oxygen diffusion, indicated by the normal A-a gradients, presumably by improving ventilation perfusion ratios and reversing etorphine-induced catatonic immobilization.

Morphine-induced acetylcholine release at the hypoglossal motor nucleus: implications for opiate-induced respiratory suppression.

The study reveals in anesthetized rats a novel morphine-induced acetylcholine release at the hypoglossal motor nucleus, which is the source of motor outflow to the genioglossus muscle of the tongue and may contribute to suppression of respiratory motor activity independent of opiate receptor mechanisms.

The potency of different serotonergic agonists in counteracting opioid evoked cardiorespiratory disturbances

5-HT1AR agonists may provide a useful tool to counteract opioid-mediated cardiorespiratory disturbances during treatment of severe pain, and are supported by the finding that 5- HT1AR was more densely expressed in key brainstem nuclei for cardiOREspiratory control compared with 5-HT4(a)R.

D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat.

  • P. Lalley
  • Biology, Medicine
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2005
The results suggest that D(1)R agonists might be therapeutically useful for the treatment of opioid disturbances of breathing without impeding analgesia.

Averting Opioid-induced Respiratory Depression without Affecting Analgesia.

None of the experimental drugs are adequate for therapeutic use in opioid-induced respiratory depression and all need further study of efficacy and toxicity, but all do highlight potential mechanisms of action and possible templates for further study and development.

Dual mechanisms of opioid-induced respiratory depression in the inspiratory rhythm-generating network

It is concluded that hyperpolarization of MOR-expressing preBötC neurons alone does not phenocopy OIRD, and the effects of MOR activation are twofold: 1) pre-inspiratory spiking is reduced and 2) excitatory synaptic transmission is suppressed, thereby disrupting network-driven rhythmogenesis.

The Counteraction of Opioid-Induced Ventilatory Depression by the Serotonin 1A-Agonist 8-OH-DPAT Does Not Antagonize Antinociception in Rats In Situ and In Vivo

5-HT1A-R-agonist 8-OH-DPAT activates spontaneous breathing without diminishing opioid-induced antinociception in rats.

Non-analgesic effects of opioids: opioid-induced respiratory depression.

A novel approach is aimed at the reduction of respiratory depression from opioid-activation of (micro-)glia cells in the pons and brainstem using micro-glia cell stabilizers which seems an attractive alternative to the classical reversal strategies with naloxone.

Selective Antagonism of Opioid‐Induced Ventilatory Depression by an Ampakine Molecule in Humans Without Loss of Opioid Analgesia

The results support the use of ampakines as selective antidotes in humans to counter opioid‐induced ventilatory depression without affecting opioid‐mediated analgesia.



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Simultaneous recordings of inspiratory and preinspiratory neuronal activities confirmed the selective inhibition ofInspatory neurons caused by &mgr;- and &kgr; -opioid receptor agonists, which caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network.

cAMP‐dependent reversal of opioid‐ and prostaglandin‐mediated depression of the isolated respiratory network in newborn rats

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Modulation of respiratory frequency by peptidergic input to rhythmogenic neurons in the preBötzinger complex.

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Normal breathing requires preBötzinger complex neurokinin-1 receptor-expressing neurons

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Pharmacological characterization of 5-hydroxytryptamine4(5-HT4) receptors positively coupled to adenylate cyclase in adult guinea pig hippocampal membranes: effect of substituted benzamide derivatives.

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Pre-Bötzinger neurons with preinspiratory discharges "in vivo" express NK1 receptors in the rat.

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International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).

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