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  • 1
    Electronic Resource
    Electronic Resource
    The rate-decreasing effects of fentanyl derivatives in pigeons before, during and after chronic morphine treatment (1998)
    Springer
    Psychopharmacology 137 (1998), S. 67-73 
    Details
    ISSN: 1432-2072
    Keywords: Key words Tolerance ; Cross-tolerance ; Dependence ; Mirfentanil ; Opioid ; Non-opioid ; Morphine ; Fentanyl ; OHM3463 ; OHM3295
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Mirfentanil is a fentanyl derivative with non-opioid actions, including non-opioid antinociceptive effects in rhesus monkeys. The current study examined the rate-altering effects of mirfentanil and several other compounds in pigeons to assess: 1) the opioid and non-opioid actions of acutely-administered fentanyl derivatives; and 2) the development of cross-tolerance between each of these compounds and morphine. Seven pigeons responded under a fixed-ratio 20 (FR20) schedule of food delivery. In untreated pigeons, fentanyl, morphine, naltrexone, ketamine and three fentanyl derivatives (mirfentanil, OHM3463 and OHM3295) decreased rates of key pecking in a dose-related manner. Naltrexone (0.1–1.0 mg/kg) attenuated the effects of OHM3463 and not mirfentanil or OHM3295, suggesting non-opioid mediation of the rate-decreasing effects for the latter two fentanyl derivatives. Subjects were treated daily with morphine for 9 weeks, up to a dose of 100 mg/kg per day, during which time the dose-effect curves for morphine, fentanyl and OHM3463 shifted rightward 6-, 10- and 2-fold, respectively, indicating the development of tolerance to morphine and cross-tolerance to fentanyl and OHM3463. Dose-effect curves for ketamine, OHM3295 and mirfentanil were not shifted to the right during morphine treatment, and the dose-effect curve for naltrexone was shifted leftward 180-fold. To the extent that rate-decreasing effects are predictive of antinociceptive effects, these data suggest that some fentanyl derivatives might be useful therapeutics under conditions where tolerance develops to morphine-like opioids.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050594
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    The discriminative stimulus effects of naloxone and naltrexone in morphine-treated rhesus monkeys: comparison of oral and subcutaneous administration (1999)
    Springer
    Psychopharmacology 144 (1999), S. 131-136 
    Details
    ISSN: 1432-2072
    Keywords: Key words Naloxone ; Naltrexone ; Rhesus monkey ; Drug discrimination ; Oral ; SC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Opioid antagonists are used to reverse the toxic effects of opioids, to diagnose opioid dependence and to treat opioid and other (alcohol) drug abuse. Objectives: This study compared the discriminative stimulus effects of two opioid antagonists (naloxone and naltrexone), after parenteral and oral administration. Methods: The discriminative stimulus effects of naloxone and naltrexone were evaluated every 15 min over a 2-h period in four morphine-treated (3.2 mg/kg per day) rhesus monkeys discriminating between subcutaneous (SC) injections of naltrexone (0.01 or 0.032 mg/kg) and saline, while responding under a fixed-ratio 5 schedule of stimulus shock termination. Results: Within 15 min of SC administration, naloxone and naltrexone produced greater than 90% drug-appropriate responding at doses of 0.032 and 0.01 mg/kg, respectively. The largest dose of naloxone (3.2 mg/kg) administered orally produced 82% drug-appropriate responding within 90 min; the same dose of naltrexone administered orally produced greater than 90% drug-appropriate responding within 30 min. Although both drugs were at least 100-fold more potent when administered SC, as compared to orally, there was little difference (3-fold) between the potency of naloxone and naltrexone by either route. Conclusions: These results fail to support the view that naloxone has reduced bioavailability after oral administration, as compared to naltrexone, or that its pharmacokinetic profile is particularly advantageous for some therapeutic settings (e.g. Talwin Nx).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050985
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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