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The effects of intravenous naltrindole and naltrindole 5'-isothiocyanate on sufentanil-induced respiratory depression and antinociception in rats. / Verborgh, C; Meert, T F.

In: Pharmacology Biochemistry and Behavior, Vol. 63, No. 1, 1999, p. 175-183.

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@article{deb8c75d5e5b415d8a47cf8a49593c50,
title = "The effects of intravenous naltrindole and naltrindole 5'-isothiocyanate on sufentanil-induced respiratory depression and antinociception in rats",
abstract = "Although the interactions between the mu- and the delta-opiate receptor subtypes are well documented with regard to supraspinal analgesia, less is known about the mutual interactions on respiratory depression. To clarify the functional interactions between both opiate receptor subtypes with regard to antinociception and respiratory depression, male Wistar rats were intravenously injected with 2.5 microg/kg of the mu-opiate agonist sufentanil and subsequently intravenously challenged with the delta antagonist naltrindole (NTI) or naltrindole 5'-isothiocyanate (5'-NTII), a delta-2 antagonist. Antinociception was measured by means of the tail-flick latency, and respiratory depression was evaluated by means of analysis of PaCO2, PaO2, and oxygen saturation. To quantify the antagonistic properties of NTI and 5'-NTII, mean areas under the curve were calculated for groups treated with sufentanil, control vehicle, and sufentanil plus a dose of the antagonists. NTI, but not 5'-NTII, antagonized the sufentanil-induced antinociception at 10 mg/kg NTI. Below this dose the effects were inconsistent. The sufentanil-induced hypercapnia and hypoxia were diminished with 10 mg/kg NTI or 5'-NTII. These data indicate that NTI antagonizes the sufentanil-induced antinociception and respiratory depression in rats. A dissociation between the antinociception and respiratory depression following intravenous sufentanil could be obtained with 10 mg/kg 5'-NTII pointing to different regulatory effects of opiate delta receptor subtypes on mu-opiate agonist-induced behavioral effects.",
keywords = "Analgesics, Opioid, Animals, Depression, Chemical, Hydrogen-Ion Concentration, Hypercapnia, Hypoxia, Isothiocyanates, Male, Naltrexone, Narcotic Antagonists, Pain Measurement, Rats, Rats, Wistar, Reaction Time, Receptors, Opioid, mu, Respiration, Sufentanil, Journal Article",
author = "C Verborgh and Meert, {T F}",
year = "1999",
language = "English",
volume = "63",
pages = "175--183",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier",
number = "1",

}

RIS

TY - JOUR

T1 - The effects of intravenous naltrindole and naltrindole 5'-isothiocyanate on sufentanil-induced respiratory depression and antinociception in rats

AU - Verborgh, C

AU - Meert, T F

PY - 1999

Y1 - 1999

N2 - Although the interactions between the mu- and the delta-opiate receptor subtypes are well documented with regard to supraspinal analgesia, less is known about the mutual interactions on respiratory depression. To clarify the functional interactions between both opiate receptor subtypes with regard to antinociception and respiratory depression, male Wistar rats were intravenously injected with 2.5 microg/kg of the mu-opiate agonist sufentanil and subsequently intravenously challenged with the delta antagonist naltrindole (NTI) or naltrindole 5'-isothiocyanate (5'-NTII), a delta-2 antagonist. Antinociception was measured by means of the tail-flick latency, and respiratory depression was evaluated by means of analysis of PaCO2, PaO2, and oxygen saturation. To quantify the antagonistic properties of NTI and 5'-NTII, mean areas under the curve were calculated for groups treated with sufentanil, control vehicle, and sufentanil plus a dose of the antagonists. NTI, but not 5'-NTII, antagonized the sufentanil-induced antinociception at 10 mg/kg NTI. Below this dose the effects were inconsistent. The sufentanil-induced hypercapnia and hypoxia were diminished with 10 mg/kg NTI or 5'-NTII. These data indicate that NTI antagonizes the sufentanil-induced antinociception and respiratory depression in rats. A dissociation between the antinociception and respiratory depression following intravenous sufentanil could be obtained with 10 mg/kg 5'-NTII pointing to different regulatory effects of opiate delta receptor subtypes on mu-opiate agonist-induced behavioral effects.

AB - Although the interactions between the mu- and the delta-opiate receptor subtypes are well documented with regard to supraspinal analgesia, less is known about the mutual interactions on respiratory depression. To clarify the functional interactions between both opiate receptor subtypes with regard to antinociception and respiratory depression, male Wistar rats were intravenously injected with 2.5 microg/kg of the mu-opiate agonist sufentanil and subsequently intravenously challenged with the delta antagonist naltrindole (NTI) or naltrindole 5'-isothiocyanate (5'-NTII), a delta-2 antagonist. Antinociception was measured by means of the tail-flick latency, and respiratory depression was evaluated by means of analysis of PaCO2, PaO2, and oxygen saturation. To quantify the antagonistic properties of NTI and 5'-NTII, mean areas under the curve were calculated for groups treated with sufentanil, control vehicle, and sufentanil plus a dose of the antagonists. NTI, but not 5'-NTII, antagonized the sufentanil-induced antinociception at 10 mg/kg NTI. Below this dose the effects were inconsistent. The sufentanil-induced hypercapnia and hypoxia were diminished with 10 mg/kg NTI or 5'-NTII. These data indicate that NTI antagonizes the sufentanil-induced antinociception and respiratory depression in rats. A dissociation between the antinociception and respiratory depression following intravenous sufentanil could be obtained with 10 mg/kg 5'-NTII pointing to different regulatory effects of opiate delta receptor subtypes on mu-opiate agonist-induced behavioral effects.

KW - Analgesics, Opioid

KW - Animals

KW - Depression, Chemical

KW - Hydrogen-Ion Concentration

KW - Hypercapnia

KW - Hypoxia

KW - Isothiocyanates

KW - Male

KW - Naltrexone

KW - Narcotic Antagonists

KW - Pain Measurement

KW - Rats

KW - Rats, Wistar

KW - Reaction Time

KW - Receptors, Opioid, mu

KW - Respiration

KW - Sufentanil

KW - Journal Article

M3 - Article

C2 - 10340539

VL - 63

SP - 175

EP - 183

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 1

ER -

ID: 36195715