remifentanil brands

Molecular formula: C20H28N2O5

Remifentanil is a µ-opioid agonist with rapid onset and peak effect, and short duration of action. The µ-opioid activity of remifentanil is antagonized by opioid antagonists such as naloxone. Remifentanil is a selective mu-receptor agonist with similar potency to fentanyl; the drug shares the actions of the opiate agonists. The drug's precise mechanism of action has not been fully elucidated; opiate agonists act at several CNS sites, involving several neurotransmitter systems to produce analgesia. Remifentanil exhibits greater affinity for the mu-receptor than for the delta- or kappa-receptors; the drug does not substantially bind to other nonopiate receptors. Agonist activity at the opiate mu-receptor can result in analgesia and respiratory depression. Respiratory depression may be mediated by mu-receptors, possibly mu2-receptors (which may be distinct from mu1-receptors involved in analgesia); kappa- and delta-receptors may also be involved in respiratory depression. Remifentanil is a powerful mu-opioid (MOP) receptor agonist used in anesthesia with a very short half-life. However, per-operative perfusion of remifentanil was shown to increase morphine consumption during post-operative period to relieve pain. In the present study, we aimed to describe the cellular mechanisms responsible for this apparent reduction of morphine efficacy. For this purpose, we first examined the pharmacological properties of both remifentanil and morphine at the MOP receptor, endogenously expressed in the human neuroblastoma SH-SY5Y cell line, to regulate adenylyl cyclase and the MAP kinase ERK1/2 pathway, their potency to promote MOP receptor phosphorylation, arrestin 3-CFP (cyan fluorescent protein) recruitment and receptor trafficking during acute and sustained exposure. In the second part of this work, we studied the effects of a prior exposure of remifentanil on morphine-induced inhibition of cAMP accumulation, activation of ERK1/2 and analgesia. We showed that sustained exposure to remifentanil promoted a rapid desensitization of opioid receptors on both signalling pathways and a pretreatment with this agonist reduced signal transduction produced by a second challenge with morphine. While both opioid agonists promoted Ser(375) phosphorylation on MOP receptor, remifentanil induced a rapid internalization of opioid receptors compared to morphine but without detectable arrestin 3-CFP translocation to the plasma membrane in our experimental conditions. Lastly, a cross-tolerance between remifentanil and morphine was observed in mice using the hot plate test. Our in vitro and in vivo data thus demonstrated that remifentanil produced a rapid desensitization and internalization of the MOP receptor that would reduce the anti-nociceptive effects of morphine. Opioids are the most effective and widely used drugs in the treatment of severe acute and chronic pain. They act through opioid receptors that belong to the family of G protein-coupled receptors. Three classes of opioid receptors (mu, delta, kappa), expressed in the central and peripheral nervous system, have been identified. The analgesic effect of opioids is mediated through multiple pathways of opioid receptor signaling (e.g., G(i/o) coupling, cAMP inhibition, Ca(++) channel inhibition). The standard exogenous opioid analgesics used in the operating room are fentanyl, sufentanil, morphine, alfentanil, and remifentanil. The ultra-short-acting mu-opioid receptor (MOR) agonist remifentanil enhances postsurgical pain when used as main anesthetic in animal models and man. Although the mechanism/s involved are poorly characterized, changes in opioid receptor expression could be a relevant feature. Using a mouse model of postoperative pain, we assessed the expression of MOR and delta opioid receptors (DORs) and the efficacy of Herpes Simplex vector-mediated proenkephalin release (SHPE) preventing postoperative nociceptive sensitization induced by remifentanil or surgical incision. We dete

Source: PubChem (NCBI) · compound 60815