Sufentanil

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🧬 Receptor activityDC

Mechanism of actionPHDM

Sufentanil is a synthetic, potent opioid with highly selective binding to μ-opioid receptors. These receptors are widely distributed in the human brain, spinal cord, and other tissues,. In general, opioids decrease cAMP (affecting neural signaling pathways), decrease neurotransmitter release, and cause membrane hyperpolarization, all of which contribute to the relief of painful symptoms. Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic neural transmission via G-proteins that activate effector proteins. Binding of the opiate receptor leads to the exchange of GTP for GDP on the G-protein complex. As the effector system is adenylate cyclase and cAMP, located at the inner surface of the plasma membrane, opioids decrease intracellular cAMP by inhibiting adenylate cyclase. The release of nociceptive neurotransmitters such as substance P, GABA, dopamine, acetylcholine, and noradrenaline is then inhibited. Opioids close N-type voltage-operated calcium channels (OP2-receptor agonist), also preventing neurotransmitter release. Sufentanil and other opioids open calcium-dependent inwardly rectifying potassium channels, resulting in hyperpolarization and reduced neuronal excitability,.
We determined the binding domains of sufentanil and lofentanil in the mu opioid receptor by comparing their binding affinities to seven mu/delta and six mu/kappa chimeric receptors with those to mu, delta and kappa opioid receptors. TMHs 6 and 7 and the e3 loop of the mu opioid receptor were important for selective binding of sufentanil and lofentanil to the mu over the kappa receptor. TMHs 1-3 and the e1 loop of the mu opioid receptor conferred binding selectivity for sufentanil over the delta receptor. Thus, the region that conferred binding selectivity for sufentanil differs, depending on chimeras used. In addition, the interaction TMHs 1-3 and TMHs 6-7 was crucial for the high affinity binding of these two ligands. These two regions are likely to contain sites of interaction with the ligands or to confer conformations specific to the mu receptor.
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.

PharmacodynamicsPH

**Effect on the Central Nervous System (CNS)** In clinical settings, sufentanil exerts its principal pharmacologic effects on the central nervous system. Its primary therapeutic actions are analgesia and sedation. Sufentanil may increase pain tolerance and decrease the perception of pain. This drug depresses the respiratory centers, depresses the cough reflex, and constricts the pupils,. When used in balanced general anesthesia, sufentanil has been reported to be as much as 10 times as potent as fentanyl. When administered intravenously as a primary anesthetic agent with 100% oxygen, sufentanil is approximately 5 to 7 times as potent as fentanyl. High doses of intravenous sufentanil have been shown to cause muscle rigidity, likely as a result of an effect on the substantia nigra and the striate nucleus in the brain. Sleep-inducing (hypnotic) activity can be demonstrated by EEG alterations. **Effects on the Respiratory System** Sufentanil may cause respiratory depression. **Effects on the Cardiovascular System** Sufentanil causes peripheral vasodilation which may result in orthostatic hypotension or syncope. Bradycardia may also occur. Clinical signs or symptoms of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes and sweating and/or orthostatic hypotension. **Effects on the Gastrointestinal Tract** Sufentanil causes a reduction in motility associated with an increase in smooth muscle tone in both the antrum of the stomach and duodenum. Digestion of food in the small intestine may be delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased and lead to spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of the sphincter of Oddi, as well as temporary elevations in serum amylase.

Pharmacokinetics

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