Conformationally Restricted Cyclic Penicillamine Analogues with High Selectivity for δ- and μ-Opioid Receptors
The concept that there are subtypes of the opiate receptor was originally suggested by Martin et al. (1976) almost a decade ago and is widely accepted based on both in vitro (Martin et al, 1976; Tyers, 1980) and in vivo (Lord et al., 1977; Schulz et al., 1980) studies. The demonstration of separate opioid target sites such as the brain (Herz et al, 1970; Jacquet and Lajtha, 1974; Pert and Yaksh, 1974; Wei et al., 1975) and spinal cord (Yaksh and Rudy, 1976, 1977) has led to the suggestion that a specific effect may be mediated by different opioid receptors at different central nervous system sites (Ling and Pasternak, 1983; Porreca and Burks, 1983). Although numerous pharmacological and biochemical studies of classical (nonpeptide) opiates and opioid peptide analogues have revealed the existence of several subclasses of receptors (e.g., μ, K, and δ, Martin et al., 1976; Gilbert and Martin, 1976; Lord et al., 1977; Chang and Cuatrecasas, 1979; Wolozin and Pasternak, 1981), it is well documented that the vast majority of opioid ligands available interact extensively with the different types of receptors, making it difficult to define receptor roles.
KeywordsOpioid Receptor Opiate Receptor Delta Opioid Receptor Radioreceptor Assay Opioid Ligand
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