Naloxonazine actions in vivo

Geoffrey Ling, Ronit Simantov, Janet A. Clark, Gavril W. Pasternak

Research output: Contribution to journalArticle

Abstract

Naloxonazine is a relatively selective μ1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for μ1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistent inhibition of binding lasting 24 h which was relatively selective for μ1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both μ1 (naloxonazine-sensitive) and a non-μ1 (naloxonazine-insensitive) components. The ratio of μ1 to non-μ1 analgesia was greater at low morphine doses, implying that morphine activated μ1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively μ1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than μ1.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalEuropean Journal of Pharmacology
Volume129
Issue number1-2
DOIs
StatePublished - Sep 23 1986
Externally publishedYes

Fingerprint

Morphine
Analgesia
Opiate Alkaloids
Affinity Labels
naloxonazine
Naloxone
Half-Life
Analgesics

Keywords

  • Morphine analgesia
  • Naloxazone
  • Naloxonazine
  • μ Receptors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ling, G., Simantov, R., Clark, J. A., & Pasternak, G. W. (1986). Naloxonazine actions in vivo. European Journal of Pharmacology, 129(1-2), 33-38. https://doi.org/10.1016/0014-2999(86)90333-X

Naloxonazine actions in vivo. / Ling, Geoffrey; Simantov, Ronit; Clark, Janet A.; Pasternak, Gavril W.

In: European Journal of Pharmacology, Vol. 129, No. 1-2, 23.09.1986, p. 33-38.

Research output: Contribution to journalArticle

Ling, G, Simantov, R, Clark, JA & Pasternak, GW 1986, 'Naloxonazine actions in vivo', European Journal of Pharmacology, vol. 129, no. 1-2, pp. 33-38. https://doi.org/10.1016/0014-2999(86)90333-X
Ling G, Simantov R, Clark JA, Pasternak GW. Naloxonazine actions in vivo. European Journal of Pharmacology. 1986 Sep 23;129(1-2):33-38. https://doi.org/10.1016/0014-2999(86)90333-X
Ling, Geoffrey ; Simantov, Ronit ; Clark, Janet A. ; Pasternak, Gavril W. / Naloxonazine actions in vivo. In: European Journal of Pharmacology. 1986 ; Vol. 129, No. 1-2. pp. 33-38.
@article{e8c774b436d04160970b25d6a8db0f86,
title = "Naloxonazine actions in vivo",
abstract = "Naloxonazine is a relatively selective μ1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for μ1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistent inhibition of binding lasting 24 h which was relatively selective for μ1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both μ1 (naloxonazine-sensitive) and a non-μ1 (naloxonazine-insensitive) components. The ratio of μ1 to non-μ1 analgesia was greater at low morphine doses, implying that morphine activated μ1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively μ1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than μ1.",
keywords = "Morphine analgesia, Naloxazone, Naloxonazine, μ Receptors",
author = "Geoffrey Ling and Ronit Simantov and Clark, {Janet A.} and Pasternak, {Gavril W.}",
year = "1986",
month = "9",
day = "23",
doi = "10.1016/0014-2999(86)90333-X",
language = "English (US)",
volume = "129",
pages = "33--38",
journal = "European Journal of Pharmacology",
issn = "0014-2999",
publisher = "Elsevier",
number = "1-2",

}

TY - JOUR

T1 - Naloxonazine actions in vivo

AU - Ling, Geoffrey

AU - Simantov, Ronit

AU - Clark, Janet A.

AU - Pasternak, Gavril W.

PY - 1986/9/23

Y1 - 1986/9/23

N2 - Naloxonazine is a relatively selective μ1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for μ1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistent inhibition of binding lasting 24 h which was relatively selective for μ1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both μ1 (naloxonazine-sensitive) and a non-μ1 (naloxonazine-insensitive) components. The ratio of μ1 to non-μ1 analgesia was greater at low morphine doses, implying that morphine activated μ1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively μ1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than μ1.

AB - Naloxonazine is a relatively selective μ1 affinity label in binding studies. Like naloxazone, naloxonazine has proven valuable in vivo in establishing a role for μ1 sites in specific opiate actions. We now report a detailed characterization of naloxonazine's actions in mice and rats. Naloxonazine antagonized morphine analgesia for greater than 24 h without altering lethality. This prolonged action could not be easily explained by a slow rate of elimination since the terminal elimination half-life was estimated at less than 3 h. Furthermore, these actions were associated with a wash-resistent inhibition of binding lasting 24 h which was relatively selective for μ1 sites. At a fixed morphine dose, increasing naloxonazine doses lowered peak tailflick latencies in a biphasic manner, suggesting that morphine analgesia consisted of both μ1 (naloxonazine-sensitive) and a non-μ1 (naloxonazine-insensitive) components. The ratio of μ1 to non-μ1 analgesia was greater at low morphine doses, implying that morphine activated μ1 analgesic mechanisms with higher affinity. Our studies also emphasized that naloxonazine has reversible actions similar to those of naloxone; only its irreversible actions are relatively μ1-selective. In addition, the selectivity of naloxonazine's irreversible actions is dose-dependent. High naloxonazine doses will irreversibly antagonize receptors other than μ1.

KW - Morphine analgesia

KW - Naloxazone

KW - Naloxonazine

KW - μ Receptors

UR - http://www.scopus.com/inward/record.url?scp=0022916415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0022916415&partnerID=8YFLogxK

U2 - 10.1016/0014-2999(86)90333-X

DO - 10.1016/0014-2999(86)90333-X

M3 - Article

C2 - 3021478

AN - SCOPUS:0022916415

VL - 129

SP - 33

EP - 38

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

SN - 0014-2999

IS - 1-2

ER -