Peptide and nonpeptide ligands for opioid receptors.

Morphine and other natural alkaloid opiates have been used in medicine for centuries. Synthesis of analogs of opiate alkaloids and primary structure activity studies have almost a hundred year history. The endogenous opioid peptides, their genetic expression and enzymatic metabolism, have been described. A number of non-peptide and peptide analogs have led to characterization of opioid receptor types (mu, delta, and kappa) and propose their subtypes. Very recently, all types of opioid receptors of different species have been characterized at the molecular level. The progressive studies of the opioid system have allowed introduction of various new types of drugs. In addition, the opioid system, as one of the best characterized, is often used as a model for studies in neurobiology as well as in bioorganic chemistry. Therefore, opioid system is a good example of the tremendous progress in medicinal chemistry, but also an illustrations of the limitations of scientific tools currently used.