Pharmacological characterization of the dermorphin analog [Dmt1]DALDA, a highly potent and selective μ-opioid peptide Journal Article
| Authors: | Neilan, C. L.; Nguyen, T. M. D.; Schiller, P. W.; Pasternak, G. W. |
| Article Title: | Pharmacological characterization of the dermorphin analog [Dmt1]DALDA, a highly potent and selective μ-opioid peptide |
| Abstract: | The dermorphin-derived peptide [Dmt1]DALDA (H-Dmt-D-Arg-Phe-Lys-NH2), labels μ-opioid receptors with high affinity and selectivity in receptor binding assays. In mouse, radiant heat tail-flick assay [Dmt1]DALDA produced profound spinal and supraspinal analgesia, being approximately 5000- and 100-fold more potent than morphine on a molar basis, respectively. When administered systemically, [Dmt1]DALDA was over 200-fold more potent than morphine. Pharmacologically, [Dmt1]DALDA was distinct from morphine. [Dmt1]DALDA displayed no cross-tolerance to morphine in the model used and it retained supraspinal analgesic activity in morphine-insensitive CXBK mice. Supraspinally, it also differed from morphine in its lack of sensitivity towards naloxonazine. Finally, in antisense mapping studies, [Dmt1]DALDA was insensitive to MOR-1 exon probes that reduced morphine analgesia, implying a distinct receptor mechanism of action. Thus, [Dmt1]DALDA is an interesting and extraordinarily potent, systemically active peptide analgesic, raising the possibility of novel approaches in the design of clinically useful drugs. © 2001 Published by Elsevier Science B.V. |
| Keywords: | controlled study; exon; nonhuman; mouse; animals; mice; animal experiment; drug potency; time factors; drug mechanism; mouse strain; morphine; pain measurement; analgesics; opioid; oligopeptides; drug sensitivity; analgesia; drug tolerance; ligand binding; mu opiate receptor; receptors, opioid, mu; tail flick test; oligodeoxyribonucleotides, antisense; naloxone; naltrexone; analgesic activity; opioid peptides; enkephalin; naloxonazine; radioligand; antisense oligodeoxynucleotide; spinal anesthesia; drug cross tolerance; narcotic antagonists; splice variant; humans; male; priority journal; article; μ-opioid receptor; dermorphin derivative; tyrosyl dextro arginylphenylalanyllysinamide; μ-opioid peptide; radioligand binding; tail-flick assay; drug receptor; mw 981 |
| Journal Title: | European Journal of Pharmacology |
| Volume: | 419 |
| Issue: | 1 |
| ISSN: | 0014-2999 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2001-05-04 |
| Start Page: | 15 |
| End Page: | 23 |
| Language: | English |
| DOI: | 10.1016/s0014-2999(01)00946-3 |
| PUBMED: | 11348625 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
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