![[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}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received for publication August 17, 2005.
Revised September 30, 2005.
Accepted for publication November 10, 2005.
Male rats are more sensitive to the antinociceptive effects of morphine than female rats. This difference is seen across several rat strains using a variety of nociceptive stimuli. However, the literature in regard to sex differences in antinociceptive response to µ-opioids other than morphine is less consistent. The present study was designed to examine if there is a structure-activity rationale that determines which µ-opioids will show a differential antinociceptive response between male and female rats. A series of morphinans closely related in structure to morphine namely codeine, heroin, hydrocodone, hydromorphone, oxymorphone and oxycodone, were examined for their antinociceptive activity in male and female Sprague Dawley rats and compared with the structurally unrelated µ-opioid agonists methadone and fentanyl. Antinociception was measured by the warm-water tail-withdrawal assay. The results show that morphine is more potent in males compared with females > hydromorphone = hydrocodone = oxymorphone, but there was no observable sex difference in the antinociceptive potency of codeine, heroin, oxycodone, methadone or fentanyl. The potency to stimulate [35S]GTP
S binding and binding affinity of the various morphinans was compared in rat glioma C6 cells expressing the rat µ-opioid receptor; relative efficacy was also compared by stimulation of [35S]GTPS binding in slices of rat brain thalamus. The presence of a sex difference in antinociceptive responsiveness was not related to drug potency, efficacy or affinity. Consequently, it is likely that differential metabolism of the opioid, possibly by glucuronidation, determines the presence or absence of a sex difference.
Key words:
G protein, antinociception, mu-opioids, rat, receptor, sex difference
This article has been cited by other articles:
|
|
 |
|
  M. S. Virk and J. T. Williams Agonist-Specific Regulation of {micro}-Opioid Receptor Desensitization and Recovery from Desensitization Mol. Pharmacol., April 1, 2008; 73(4): 1301 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Gupta, H. von Gizycki, and A. R. Gintzler Sex-/Ovarian Steroid-Dependent Release of Endomorphin 2 from Spinal Cord J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 635 - 641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Shuey, C. Woodland, C. Tremblay, R. Gregson, and R. J. Gerson Oxymorphone Hydrochloride, a Potent Opioid Analgesic, Is Not Carcinogenic in Rats or Mice Toxicol. Sci., March 1, 2007; 96(1): 162 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Claiborne, S. Nag, and S. S. Mokha Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male J. Neurosci., December 13, 2006; 26(50): 13048 - 13053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Bostrom, U. S. H. Simonsson, and M. Hammarlund-Udenaes In Vivo Blood-Brain Barrier Transport of Oxycodone in the Rat: Indications for Active Influx and Implications for Pharmacokinetics/Pharmacodynamics Drug Metab. Dispos., September 1, 2006; 34(9): 1624 - 1631. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
