Development of Receptor-Selective Opioid Peptide Analogs as Pharmacologic Tools and as Potential Drugs

摘要: Much progress has been made in the elucidation of opioid receptor heterogeneity during past 15 years. The existence three major types (μ, δ, ĸ) (MARTIN et al. 1976; LORD 1977) is now firmly established and there strong evidence favor a fourth type, c–receptor (SCHULZ 1979). More recently obtained physiological binding data led to proposal various subtypes (μ1, μ2, ĸ1, ĸ2, ĸ3) (reviewed CLARK 1989). Opioids produce large variety well-known central peripheral effects, including spinal supraspinal analgesia, tolerance physical dependence, respiratory depression, euphoria, dysphoria hallucinations, sedation, appetite suppression other behavioral control release several hormones neurotransmitters, effects on gastrointestinal motility, hyperthermia/hypothermia, cardiovascular tumor growth, immune response. Both for role(s) classes development opioid-derived drugs it great importance establish clear-cut correlations between specific distinct effects. For this purpose further efforts are needed develop agonists antagonists with high selectivity subtypes. fact that morphine displays only limited μ-receptor well known characterization peptides generated through processing mammalian precursors showed none them very selective HoLLT 1986).