Sex differences in opioid antinociception in rhesus monkeys: antagonism of fentanyl and U50,488 by quadazocine
Open accessAbstract
Sex differences have been observed in the antinociceptive effects of opioids in rodents and rhesus monkeys. Sex differences in the affinity of opioid ligands for opioid receptors may contribute to these findings. To test this hypothesis, the relative affinity of the competitive opioid antagonist quadazocine for mu and kappa opioid receptors was determined in rhesus monkeys using in vivo pA(2) analysis. The antinociceptive effects of the mu opioid agonist fentanyl and the kappa opioid agonist U50,488 were determined alone and after pretreatment with quadazocine in 4 females and 4 males using a warm-water tail-withdrawal assay of thermal nociception. The relative potency of quadazocine antagonism of fentanyl and U50,488 in females and males was used to assess sex differences in the relative affinity of quadazocine for mu and kappa receptors. Fentanyl was equipotent in female and male monkeys, and quadazocine was equipotent as an antagonist of fentanyl in females and males. In contrast, U50,488 was significantly less potent in females, and quadazocine was less potent as an antagonist of U50,488 in females. These findings suggest that opioid ligands have similar affinity for mu receptors but lower affinity for at least some kappa receptors in female than in male rhesus monkeys.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The Physiology of Reproduction
Legendre, M., & Jalabert, B. (1988) · Annals of Internal Medicine · doi:10.7326/0003-4819-109-2-176_1 · Cited by 7,879 · see citing works
Pharmacologic Analysis of Drug Receptor Interaction
Kenakin, K. T. (1988) · Therapeutic Drug Monitoring · doi:10.1097/00007691-198803000-00029 · Cited by 932 · see citing works
Endocrine consequences of long-term intrathecal administration of opioids
Abs, R., Verhelst, J., Maeyaert, J., Van Buyten, J.-P., Opsomer, F., Adriaensen, H., Verlooy, J., Van Havenbergh, T., Smet, M., & Van Acker, K. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.6.6615 · Cited by 491 · see citing works
Gender differences in the responses to noxious stimuli
Fillingim, R. B., & Maixner, W. D. (1995) · Pain Forum · doi:10.1016/s1082-3174(11)80022-x · Cited by 475 · see citing works
Kappa–opioids produce significantly greater analgesia in women than in men
Gear, R. W., Miaskowski, C. A., Gordon, N. C., Paul, S. M., Heller, P. H., & Levine, J. D. (1996) · Nature Medicine · doi:10.1038/nm1196-1248 · Cited by 457 · see citing works
Manual of Pharmacologic Calculations
Tallarida, R. J., & Murray, R. B. (1987) · Springer eBooks · doi:10.1007/978-1-4612-4974-0 · Cited by 429 · see citing works
Sex Differences in Morphine Analgesia
Sarton, E. Y., Olofsen, E., Romberg, R. R., den Hartigh, J., Kest, B., Nieuwenhuijs, D. J. F., Burm, A. G. L., Teppema, L. J., & Dahan, A. (2000) · Anesthesiology · doi:10.1097/00000542-200011000-00018 · Cited by 360 · see citing works
Sex differences in thermal nociception and morphine antinociception in rodents depend on genotype
Mogil, J. S., Chesler, E. J., Wilson, S. G., Juraska, J. M., & Sternberg, W. F. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00015-4 · Cited by 346 · see citing works
Gender and Age Influences on Human Brain Mu-Opioid Receptor Binding Measured by PET
Zubieta, J., Dannals, R. F., & Frost, J. J. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.6.842 · Cited by 335 · see citing works
Sex Differences in Opioid Analgesia: “From Mouse to Man”
Craft, R. M. (2003) · Clinical Journal of Pain · doi:10.1097/00002508-200305000-00005 · Cited by 319 · see citing works
Pharmacologic analysis of drug-receptor interaction
Netter, K. J. (1994) · Toxicology · doi:10.1016/0300-483x(94)90086-8 · Cited by 285 · see citing works
Gear, R. W., Miaskowski, C. A., Gordon, N. C., Paul, S. M., Heller, P. H., & Levine, J. D. (1999) · Pain · doi:10.1016/s0304-3959(99)00119-0 · Cited by 275 · see citing works
Gender-related differences in the antinociceptive properties of morphine.
Cicero, T. J., Nock, B. L., & Meyer, E. R. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)21187-9 · Cited by 263 · see citing works
Kepler, K. L., Kest, B., Kiefel, J. M., Cooper, M. L., & Bodnar, R. J. (1989) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(89)90363-8 · Cited by 234 · see citing works
Emmerson, P. J., Liu, M. R., Woods, J. H., & Medzihradsky, F. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24051-4 · Cited by 232 · see citing works
Ischemic but Not Thermal Pain Sensitivity Varies Across the Menstrual Cycle
Fillingim, R. B., Maixner, W. D., Girdler, S. S., Light, K. C., Harris, M. B., Sheps, D. S., & Mason, G. (1997) · Psychosomatic Medicine · doi:10.1097/00006842-199709000-00008 · Cited by 197 · see citing works
Gender effects and central opioid analgesia
Kepler, K. L., Standifer, K. M., Paúl, D., Kest, B., Pasternak, G. W., & Bodnar, R. J. (1991) · Pain · doi:10.1016/0304-3959(91)90168-w · Cited by 184 · see citing works
Emmerson, P. J., Clark, M. J., Mansour, A., Akil, H., Woods, J. H., & Medzihradsky, F. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20761-3 · Cited by 182 · see citing works
Cicero, T. J., Nock, B. L., & Meyer, E. R. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36831-4 · Cited by 174 · see citing works
Cook, C. D., Barrett, A. C., Roach, E. L., Bowman, J. R., & Picker, M. J. (2000) · Psychopharmacology · doi:10.1007/s002130000453 · Cited by 167 · see citing works
Sex Differences in Opioid Antinociception
Bartok, R. E., & Craft, R. M. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36827-2 · Cited by 167 · see citing works
Estrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms
Dawson-Basoa, M. E., & Gintzler, A. R. (1996) · Pain · doi:10.1016/0304-3959(95)00092-5 · Cited by 149 · see citing works
Sex-related differences in the effects of morphine and stress on visceral pain
Baamonde, A., Hidalgo, A., & Andres-Trelles, F. (1989) · Neuropharmacology · doi:10.1016/0028-3908(89)90197-4 · Cited by 138 · see citing works
Interactions among aging, gender, and gonadectomy effects upon morphine antinociception in rats
Islam, A. K., Cooper, M. L., & Bodnar, R. J. (1993) · Physiology & Behavior · doi:10.1016/0031-9384(93)90042-e · Cited by 128 · see citing works
Enhancement of morphine analgesia by the GABAB agonist baclofen
Gordon, N. C., Gear, R. W., Heller, P. H., Paul, S. M., Miaskowski, C. A., & Levine, J. D. (1995) · Neuroscience · doi:10.1016/0306-4522(95)00335-g · Cited by 117 · see citing works
Boyer, J. S., Morgan, M. M., & Craft, R. M. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00353-9 · Cited by 115 · see citing works
Transduction Mechanisms of Drug Stimuli
Colpaert, F. C., Balster, R. L., & Dependency, S. (1988) · Medical Entomology and Zoology · Cited by 114 · see citing works
Effect of adrenal and sex hormones on opioid analgesia and opioid receptor regulation
Candido, J., Lutfy, K., Billings, B., Sierra, V., Duttaroy, A., Inturrisi, C. E., & Yoburn, B. C. (1992) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(92)90015-8 · Cited by 109 · see citing works
Kavaliers, M., & Innes, D. G. L. (1987) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(87)90351-0 · Cited by 103 · see citing works
Sex-Dependent Components of the Analgesia Produced by Athletic Competition
Sternberg, W. F., Boka, C., Kass, L. K., Alboyadjia, A., & Gracely, R. H. (2001) · Journal of Pain · doi:10.1054/jpai.2001.18236 · Cited by 102 · see citing works
Negus, S. S., & Mello, N. K. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35015-3 · Cited by 102 · see citing works
Self-citationButelman, E. R., Negus, S. S., Ai, Y., de Costa, B. R., & Woods, J. H. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39577-7 · Cited by 99 · see citing works
Self-citationNegus, S. S., Burke, T. F., Medzihradsky, F., et al. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39549-2 · Cited by 98 · see citing works
Self-citationNovak, K. (2003) · Nature reviews. Cancer · doi:10.1038/nrc988 · Cited by 96 · see citing works
Sex differences in opioid antinociception: κ and ‘mixed action’ agonists
Craft, R. M., & Bernal, S. A. (2001) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(00)00209-x · Cited by 95 · see citing works
Noise Stress and Human Pain Thresholds: Divergent Effects in Men and Women
Rhud, J. L., & Meagher, M. W. (2001) · Journal of Pain · doi:10.1054/jpai.2000.19947 · Cited by 82 · see citing works
Does opioid analgesia show a gender preference for females?
Miaskowski, C. A., & Levine, J. D. (1999) · Pain Forum · doi:10.1016/s1082-3174(99)70044-9 · Cited by 80 · see citing works
Opioid Efficacy in a C6 Glioma Cell Line Stably Expressing the Human Kappa Opioid Receptor
Remmers, A. E., Clark, M. J., Mansour, A., et al. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38026-7 · Cited by 76 · see citing works
Sex differences in discriminative stimulus effects of morphine in the rat.
Craft, R. M., Kalivas, P. W., & Stratmann, J. A. (1996) · PubMed · Cited by 75 · see citing works
Ko, M., Butelman, E. R., Traynor, J. R., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37416-6 · Cited by 72 · see citing works
Opioid thermal antinociception in rhesus monkeys: receptor mechanisms and temperature dependency.
Walker, E. A., Butelman, E. R., DeCosta, B. R., & Woods, J. H. (1993) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39351-1 · Cited by 72 · see citing works
Dykstra, L. A., Gmerek, D. E., Winger, G. D., et al. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39098-1 · Cited by 66 · see citing works
Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities.
France, C. P., Medzihradsky, F., & Woods, J. H. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38497-1 · Cited by 61 · see citing works
Butelman, E. R., Ko, M., Sobczyk‐Kojiro, K., et al. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37419-1 · Cited by 60 · see citing works
Bertalmio, A. J., & Woods, J. H. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)11013-6 · Cited by 56 · see citing works
μ-Opiate receptor binding is up-regulated in mice selectively bred for high stress-induced analgesia
Mogil, J. S., Marek, P., O’Toole, L. A., Helms, M. L., Sadowski, B., Liebeskind, J. C., & Belknap, J. K. (1994) · Brain Research · doi:10.1016/0006-8993(94)90366-2 · Cited by 50 · see citing works
The Effects of Chronic Cocaine Self-Administration on the Menstrual Cycle in Rhesus Monkeys
Mello, N. K., Mendelson, J. H., Kelly, M., Diaz-Migoyo, N., & Sholar, J. W. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36607-8 · Cited by 48 · see citing works
Self-citationAction of naloxone on gender-dependent analgesic and antianalgesic effects of nalbuphine in humans
Gear, R. W., Miaskowski, C. A., Gordon, N. C., Paul, S. M., Heller, P. H., & Levine, J. D. (2000) · Journal of Pain · doi:10.1016/s1526-5900(00)90097-x · Cited by 36 · see citing works
Negus, S. S., & Mello, N. K. (2001) · Psychopharmacology · doi:10.1007/s002130100912 · Cited by 33 · see citing works
Self-citationEstrogen and progesterone activate spinal kappa-opiate receptor analgesic mechanisms
Dawson-Basoa, M. E., & Gintzler, A. R. (1996) · Pain · doi:10.1016/0304-3959(96)00032-2 · Cited by 33 · see citing works
kappa-Opioid receptor effects of butorphanol in rhesus monkeys.
Vivian, J. A., DeYoung, M. B., Sumpter, T. L., Traynor, J. R., Lewis, J. W., & Woods, J. H. (1999) · PubMed · Cited by 31 · see citing works
Inhibitory effect of a new opioid agonist on reproductive endocrine activity in rats of both sexes
Markó, M., & Römer, D. (1983) · Life Sciences · doi:10.1016/0024-3205(83)90381-8 · Cited by 29 · see citing works
Effects of Drugs of Abuse on Reproductive Function in Women and Pregnancy
TEOH, S. K., Mello, N. K., & Mendelson, J. H. (1994) · Humana Press eBooks · doi:10.1007/978-1-4612-0299-8_17 · Cited by 20 · see citing works
Self-citation(1994) · Humana Press eBooks · doi:10.1007/978-1-4612-0299-8 · Cited by 15 · see citing works
κ-Opioid Receptor Effects of Butorphanol in Rhesus Monkeys
Vivian, J. A., DeYoung, M. B., Sumpter, T. L., et al. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)34893-1 · Cited by 14 · see citing works
κ-Opioid receptor-mediated analgesia: hotplate temperature and sex differences
van Haaren, F., Scott, S. M., & Tucker, L. B. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00769-x · Cited by 12 · see citing works
Gatch, M. B., Negus, S. S., Mello, N. K., et al. (1996) · European Journal of Pharmacology · doi:10.1016/0014-2999(95)00769-5 · Cited by 12 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [41]41. Negus SS: Sex and gonadal steroid hormone levels as determinants of opioid antinociception in rhesus monkeys. NIDA Res Monogr in press
Cited by
Sorted by citations
Sex Differences in Animal Models: Focus on Addiction
Becker, J. B., & Koob, G. F. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.011163 · Cited by 725 · see citing works
Neurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477 · see citing works
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337 · see citing works
- Authors
- Negus, S. S., Zuzga, D. S., & Mello, N. K.
- Affiliations
- Harvard University (US)
- Venue
- The Journal of Pain
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 3
- Issue
- 3
- Pages
- 218-226
- ISSN
- 1526-5900 (ISSN-L)
- OpenAlex
- W2016310385
- Cited by
- 39
- References
- 57
- Citations by year
- 2026: 3 · 2025: 2 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 1 · 2016: 2 · 2015: 1 · 2013: 2 · 2012: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Pain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- sex differences, opioid antinociception, fentanyl, U50,488, mu-opioid receptor, kappa opioid receptor, receptor binding affinity, competitive antagonists, thermal nociception, rhesus monkeys
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
