Pain is a most common clinical condition and most disturbing symptom for patients, especially for postoperative patients and patients suffering from chronic paining diseases or cancer. Postoperative analgesia currently is still dominated by opioid analgesics alone, with high incidences of respiratory depression, nausea, vomiting, pruritus and other complications, which add new concerns to patients with postoperative analgesia.
In recent years, dezocine has been widely used both at home and abroad as a novel mixed agonistic antagonist of opioid receptor. It has a good analgesic effect and less adverse reactions. Dezocine is an artificially synthesized compound having a benzobicycloalkane structure and is a mixed opioid receptor agonist-antagonist. Dezocine reduces the incidence of respiratory depression and addiction with extremely weak activity on δ opioid receptor and thus no irritability and anxiety. Therefore, it is widely used in clinical postoperative analgesia.
However, one of the main disadvantages of dezocine is poor oral bioavailability (no greater than 5%), which leads to the current use of dezocine as an injection form. Another disadvantage of dezocine is small administration window, with no obvious effect at low doses and enhanced effect yet also significantly increased risk of adverse reactions as the dose is gradually increased. Therefore, in order to ensure a stable dosing concentration, it is typically a perfusion administration in clinical practice. However, the injections are not only inconvenient, but also have a short onset time of about 2-3 hours, after which the plasma concentration drops below the effective level and the drug effect disappears. In addition, large doses increase clinically risk of respiratory depression, nausea, vomiting, pruritus and other adverse reactions due to fast elimination of plasma concentration.
Therefore, it is of great necessarity to develop novel dezocine analogues to increase oral bioavailability, prolong onset time, maintain constant plasma concentrations, reduce clinical adverse reactions, and provide better drug selection and better compliance for clinical patients.
USPTO Backgrounds
USPTO Backgrounds