SELECTION CRITERIA OF COMPOUNDS FOR DEVELOPMENT OF HIGH-POTENT ANALGESICS AND OTHER CNS DRUGS

Abstract

The global opioid crisis requires a paradigm shift in medical use of opioids, the development of methodology to reduce illicit drug use, and development of drug addiction treatment and antidotes. USA target program - HEAL Initiative is implemented under the scientific guidance of NIH with active participation of FDA, CDC and military medicine institutions. The situation in Russian Federation is characterized by a combination of high illegal consumption of dangerous opioids with an extreme shortage of potent analgesics, drugs for treatment addiction and overdose and rudimentary choice of drug formulations. There isn’t any development of innovative substances and preparations of strong analgesics and antidotes, but also a competent analysis of the subject area and vision of directions for the development. The data analysis shows need to replace some of traditionally used mostly natural and semi-synthetic narcotic analgesics (with low therapeutic index, unsatisfactory pharmacokinetics and severe side effects) to promising synthetic opioids and non-narcotic analgesics. Use of prodrugs, synergistic combinations, conjugates and co-drugs is justified. Prospective dosage forms of compounds and pharmaceutical preparations for development of wide range of improved therapeutics should combine: high analgesicactivity, high therapeutic index, minimum values of Tmax and t1/2ke0, positive values of LogBB, distribution coefficient logD7,4 in the interval from 1 to 3. This combination of key properties is necessary for effectiveness and safety of CNS-specific drugs and also allows development on their basis wide range of dosage forms (injectable and non-injectable drugs, fast-acting and prolonged drugs). First of all it is desirable to replace some obsolete injecting and oral preparations (especially with fast and uncontrolled release) to fast-acting transmucosal formulations with targeted pharmacokinetic properties. In order to analyze best practices, develop a strategy for highly effective controlled medicinal and veterinary drugs (analgesics, anesthetics, antidotes and other vital therapies) and coordinate theirdevelopment and production it is necessary to create competent management structure combining the tasks of provision of civilian population and personnel of national defense agencies of effective and safe drugs.

Keywords

• analgesic
• opioid
• morphine
• oliceridine
• fentanyl analogues
• prodrug
• co-drug
• opioid crisis
• morphine equivalent
• therapeutic index
• distribution coefficient
• pharmacokinetics
• non-injectable dosage form
• antidote