JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (11)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cox, R. F.
Right arrow Articles by Collins, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cox, R. F.
Right arrow Articles by Collins, M. A.
Related Collections
Right arrow Pharmacology
Anesth Analg 2001;93:354-358
© 2001 International Anesthesia Research Society


ANESTHETIC PHARMACOLOGY

The Effects of Benzodiazepines on Human Opioid Receptor Binding and Function

Richard F. Cox, PhD*, and Mark A. Collins{dagger}

Departments of *Receptor Biochemistry and {dagger}Molecular Pharmacology, GlaxoSmithKline, Research Triangle Park, North Carolina

Address correspondence and reprint requests to Richard F. Cox, PhD, Systems Research, GlaxoSmithKline, Research Triangle Park, NC 27709. Address e-mail to rc7694{at}glaxowellcome.com

We performed in vitrostudies to investigate the potential interaction of benzodiazepines with cloned human opioid receptor subtypes. Midazolam, chlordiazepoxide, and diazepam directly displaced [3H]-diprenorphine binding from {kappa} and {delta} receptors, but not µ receptors, whereas flumazenil was inactive. These benzodiazepines also stimulated 35S-GTP{gamma}S binding in membranes containing human {kappa} receptors, and the effect of midazolam was prevented by a selective {kappa} antagonist. Midazolam was also weakly active at {delta}-receptor activation, whereas all three were inactive at µ receptors. The results suggest that the analgesic efficacy reported for intrathecal benzodiazepines may be attributed, in part, to direct interaction with {kappa}-opioid receptors.

IMPLICATIONS: Several human and animal studies have shown analgesic effects of benzodiazepines after spinal injection. Our results show that large concentrations of midazolam, chlordiazepoxide, and diazepam displace the binding of [3H]-diprenorphine—an opiate radioligand from {kappa} receptors. In an in vitrofunctional assay, midazolam is a weak agonist at the {delta}-opioid receptor, whereas all three benzodiazepines are {kappa}-opioid agonists. These findings may partially explain the mechanism of benzodiazepine-induced spinal analgesia.




This article has been cited by other articles:


Home page
Anesth. Analg.Home page
Y. K. Batra, R. Mahajan, S. Kumar, S. Rajeev, and M. Singh Dhillon
A Dose-Ranging Study of Intraarticular Midazolam for Pain Relief After Knee Arthroscopy
Anesth. Analg., August 1, 2008; 107(2): 669 - 672.
[Abstract] [Full Text] [PDF]


Home page
Cereb CortexHome page
S. Yamamoto, J. Yamada, S. Ueno, H. Kubota, T. Furukawa, S. Yamamoto, and A. Fukuda
Insertion of {alpha}7 Nicotinic Receptors at Neocortical Layer V GABAergic Synapses Is Induced by a Benzodiazepine, Midazolam
Cereb Cortex, March 1, 2007; 17(3): 653 - 660.
[Abstract] [Full Text] [PDF]


Home page
J PsychopharmacolHome page
J. C. Scaife, R. H. Hou, E. R. Samuels, F. Baqui, R. W. Langley, C. M. Bradshaw, and E. Szabadi
Diazepam-induced disruption of classically-conditioned fear-potentiation of late-latency auditory evoked potentials is prevented by flumazenil given before, but not after, CS/US pairing
J Psychopharmacol, January 1, 2007; 21(1): 93 - 101.
[Abstract] [PDF]


Home page
J PsychopharmacolHome page
J. C. Scaife, R. W. Langley, C. M. Bradshaw, and E. Szabadi
Diazepam suppresses the acquisition but not the expression of 'fearpotentiation' of the acoustic startle response in man
J Psychopharmacol, July 1, 2005; 19(4): 347 - 356.
[Abstract] [PDF]


Home page
Hum Exp ToxicolHome page
S W Borron, C Monier, P Risede, and F J Baud
Flunitrazepam variably alters morphine, buprenorphine, and methadone lethality in the rat
Human and Experimental Toxicology, November 1, 2002; 21(11): 599 - 605.
[Abstract] [PDF]




Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2001 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press
Copyright © 2001 by the International Anesthesia Research Society.