This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Pasternak, G. W. Search for Related Content PubMed PubMed Citation Articles by Pasternak, G. W. Social Bookmarking                         What's this?

Book Review: The Pharmacology of Mu Analgesics: From Patients to Genes

Laboratory of Molecular Neuropharmacology, Memorial Sloan-Kettering Cancer Center, New York, pasterng{at}mskmail.mskcc.org

Morphine and most clinical opioids act through mu opioid receptors. Yet, their pharmacological profiles differ. The presence of incomplete cross-tolerance among these drugs clinically was one of the first indications that these mu opioids differed in their receptor mechanisms of action. This was followed by similar studies in preclinical models, which also found genetic differences in sensitivity toward morphine and other mu opioids. This concept of mu receptor multiplicity is now supported by antisense and gene knockout models. Although all the mu opioids are sensitive to antisense probes against the mu opioid receptor gene MOR-1, the sensitivity profiles of the drugs to the antisense probes differ based on the exon being targeted. Knockout mice also reveal striking differences. In one knockout mouse, morphine analgesia is completely lost while the potent mu drugs morphine-6β-glucuronide and heroin both retain analgesic activity. Finally, cloning studies have identified at least seven different splice variants of the MOR-1 gene, with more likely. These studies illustrate the complexity of mu opioid pharmacology.

Key Words: Opioid • Morphine • Opioid receptor • Heroin • Mu receptor • Cross-tolerance • Splicing

The Neuroscientist, Vol. 7, No. 3, 220-231 (2001)
DOI: 10.1177/107385840100700307


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				V. Fernandez-Duenas, O. Pol, P. Garcia-Nogales, L. Hernandez, E. Planas, and M. M. Puig Tolerance to the Antinociceptive and Antiexudative Effects of Morphine in a Murine Model of Peripheral Inflammation J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 360 - 368. [Abstract] [Full Text] [PDF]

				J. C. Ballantyne Chronic Pain Following Treatment for Cancer: The Role of Opioids Oncologist, December 1, 2003; 8(6): 567 - 575. [Abstract] [Full Text] [PDF]

				J. C. Ballantyne and J. Mao Opioid Therapy for Chronic Pain N. Engl. J. Med., November 13, 2003; 349(20): 1943 - 1953. [Full Text] [PDF]

				J. Gardner-Nix Opioids and chronic pain Can. Med. Assoc. J., October 28, 2003; 169(9): 904 - 904. [Full Text]

				C. L. Neilan, A. J. Janvey, E. Bolan, I. Berezowska, T. M.-D. Nguyen, P. W. Schiller, and G. W. Pasternak Characterization of the Binding of [3H][Dmt1]H-Dmt-D-Arg-Phe-Lys-NH2, a Highly Potent Opioid Peptide J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 430 - 436. [Abstract] [Full Text] [PDF]

				J. Gardner-Nix Principles of opioid use in chronic noncancer pain Can. Med. Assoc. J., July 8, 2003; 169(1): 38 - 43. [Full Text] [PDF]