Opioids pp 681-710 | Cite as

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

  • P. W. Schiller
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 104 / 1)


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


Opioid Receptor Opioid Peptide Photoaffinity Label Bivalent Ligand Pept Protein 
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  • P. W. Schiller

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