The Last Decade of Antinociceptive Alkaloids: Structure, Synthesis, Mechanism of Action and Prospect

High molecular diversity of natural products (NPs) can provide a solution for many serious medicinal conditions. Frequently attributed with strong and useful biological/pharmacological properties, NPs may be directly applied in therapy, or could serve as templates for future drugs. As pain is a major symptom in many illnesses, and can significantly interfere with a person's quality of life and general functioning, pain-killing potential is certainly among the most highly valued features of any newly discovered, potentially pharmacologically useful molecule. Inspired by the fact that some of the most famous and powerful analgesic/antinociceptive agents are natural (plant) alkaloids (e.g. codeine, morphine), or are derived from them (oxycodone), herein we have tried to systematize recent findings (accumulated during the last decade) on molecular structure, mechanism of antinociceptive/analgesic action and synthesis of pain-killing alkaloids. In other words, this review tries to find out whether it is possible to give a general answer to the following questions: Which (new) structures are active? How can we obtain them? What do they do to the organism? How do they do that (structureactivity relationship)? And what can we do to them to make them better (i.e. could they be used as potential leads for new antinociceptive drugs)?