![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 289, Issue 1, 494-502, April 1999
Adolor Corporation, Malvern, Pennsylvania (D.L.D.-H., L.C.B.,
J.A.C., J.D.D., R.N.D, E.M., G.Y.); and
Department of Anesthesiology,
University of California at San Diego, La Jolla, California (H.N.,
T.Y.)
The antihyperalgesic properties of the opiate
antidiarrheal agent loperamide (ADL 2-1294) were investigated in a
variety of inflammatory pain models in rodents. Loperamide exhibited
potent affinity and selectivity for the cloned µ (Ki = 3 nM) compared with the 
(Ki = 48 nM) and 
(Ki = 1156 nM) human opioid receptors. Loperamide potently stimulated
[35S]guanosine-5'-O-(3-thio)triphosphate
binding (EC50 = 56 nM), and inhibited forskolin-stimulated
cAMP accumulation (IC50 = 25 nM) in Chinese hamster ovary
cells transfected with the human µ opioid receptor. The injection of
0.3 mg of loperamide into the intra-articular space of the inflamed rat
knee joint resulted in potent antinociception to knee compression that
was antagonized by naloxone, whereas injection into the contralateral
knee joint or via the i.m. route failed to inhibit compression-induced
changes in blood pressure. Loperamide potently inhibited late-phase
formalin-induced flinching after intrapaw injection (A50 = 6 µg) but was ineffective against early-phase flinching or after
injection into the paw contralateral to the formalin-treated paw. Local
injection of loperamide also produced antinociception against Freund's
adjuvant- (ED50 = 21 µg) or tape stripping-
(ED50 = 71 µg) induced hyperalgesia as demonstrated by
increased paw pressure thresholds in the inflamed paw. In all animal
models examined, the potency of loperamide after local administration
was comparable to or better than that of morphine. Loperamide has
potential therapeutic use as a peripherally selective opiate
antihyperalgesic agent that lacks many of the side effects generally
associated with administration of centrally acting opiates.
This article has been cited by other articles:
|
|
 |
|
  E. R. Butelman, S. Rus, D. S. Simpson, A. Wolf, T. E. Prisinzano, and M. J. Kreek The Effects of Herkinorin, the First {micro}-Selective Ligand from a Salvinorin A-Derived Scaffold, in a Neuroendocrine Biomarker Assay in Nonhuman Primates J. Pharmacol. Exp. Ther., October 1, 2008; 327(1): 154 - 160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. V. Vasilyev, Q. Shan, Y. Lee, S. C. Mayer, M. R. Bowlby, B. W. Strassle, E. J. Kaftan, K. E. Rogers, and J. Dunlop Direct Inhibition of Ih by Analgesic Loperamide in Rat DRG Neurons J Neurophysiol, May 1, 2007; 97(5): 3713 - 3721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Ji, A. Z. Murphy, and R. J. Traub Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R307 - R314. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Michaelis, M. M. Hoffmann, S. Dreis, E. Herbert, R. N. Alyautdin, M. Michaelis, J. Kreuter, and K. Langer Covalent Linkage of Apolipoprotein E to Albumin Nanoparticles Strongly Enhances Drug Transport into the Brain J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1246 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bileviciute-Ljungar, M. Spetea, Y. Guo, J. Schutz, P. Windisch, and H. Schmidhammer Peripherally Mediated Antinociception of the {micro}-Opioid Receptor Agonist 2-[(4,5{alpha}-Epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino]acetic Acid (HS-731) after Subcutaneous and Oral Administration in Rats with Carrageenan-Induced Hindpaw Inflammation J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 220 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Cook and M. D. Nickerson Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 449 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Butelman, T. J. Harris, and M. J. Kreek Antiallodynic Effects of Loperamide and Fentanyl against Topical Capsaicin-Induced Allodynia in Unanesthetized Primates J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Valenzano, W. Miller, Z. Chen, S. Shan, G. Crumley, S. F. Victory, E. Davies, J.-C. Huang, N. Allie, S. J. Nolan, et al. DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic Acid), a Novel, Systemically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: I. In Vitro Pharmacological Characterization and Pharmacokinetic Properties J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 783 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Whiteside, J. E. Harrison, M. S. Pearson, Z. Chen, Y. Rotshteyn, P. I. Turchin, J. D. Pomonis, L. Mark, K. Walker, and K. C. Brogle DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic Acid), a Novel, Systemically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: II. In Vivo Pharmacological Characterization in the Rat J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 793 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Tasatargil and G. Sadan Reduction in [D-Ala2, NMePhe4, Gly-ol5]Enkephalin-Induced Peripheral Antinociception in Diabetic Rats: The Role of the L-Arginine/Nitric Oxide/Cyclic Guanosine Monophosphate Pathway Anesth. Analg., January 1, 2004; 98(1): 185 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J Fioramonti and L Bueno Centrally acting agents and visceral sensitivity Gut, July 1, 2002; 51(90001): i91 - 95. [Abstract] [Full Text]
|
|
|
|
 |
|
 B. L. Kidd and L. A. Urban Mechanisms of inflammatory pain Br. J. Anaesth., July 1, 2001; 87(1): 3 - 11. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
