Selective antagonism of opioid-induced ventilatory depression by an ampakine molecule in humans without loss of opioid analgesia
| Autor: | Jörn Lötsch, John J. Greer, Helmut Schmidt, Bruno G. Oertel, M A Varney, S Johnson, Gerd Geisslinger, Lisa Felden, Martin S. Angst, P V Tran, M H Bradshaw |
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| Rok vydání: | 2009 |
| Předmět: |
Ampakine
Adult Male medicine.drug_class CX717 Narcotic Antagonists Administration Oral Pain (+)-Naloxone Pharmacology Placebo law.invention Hypercapnia chemistry.chemical_compound Young Adult Double-Blind Method law medicine Humans Pharmacology (medical) Alfentanil Depression (differential diagnoses) Clinical pharmacology Cross-Over Studies business.industry Naloxone Isoxazoles Analgesics Opioid Oxygen Opioid chemistry Anesthesia business Respiratory Insufficiency medicine.drug |
| Zdroj: | Clinical pharmacology and therapeutics. 87(2) |
| ISSN: | 1532-6535 |
| Popis: | Ventilatory depression is a significant risk associated with the use of opioids. We assessed whether opioid-induced ventilatory depression can be selectively antagonized by an ampakine without reduction of analgesia. In 16 healthy men, after a single oral dose of 1,500 mg of the ampakine CX717, a target concentration of 100 ng/ml alfentanil decreased the respiratory frequency by only 2.9 ± 33.4% as compared with 25.6 ± 27.9% during placebo coadministration (P < 0.01). Blood oxygenation and the ventilatory response to hypercapnic challenge also showed significantly smaller decreases with CX717 than with placebo. In contrast, CX717 did not affect alfentanil-induced analgesia in either electrical or heat-based experimental models of pain. Both ventilatory depression and analgesia were reversed with 1.6 mg of naloxone. These results support the use of ampakines as selective antidotes in humans to counter opioid-induced ventilatory depression without affecting opioid-mediated analgesia. Clinical Pharmacology & Therapeutics (2010) 87 2, 204–211. doi:10.1038/clpt.2009.194 |
| Databáze: | OpenAIRE |
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