The interaction of naloxonazine, a putative long lasting or "irreversible" mu$ sb1$ receptor antagonist, with morphine, morphine-6-glucuronide (M6G) and sufentanil was studied in two nociceptive tests using rats, the formalin test and the tail-immersion test. Also, the displacement of ($ sp3$H) naloxone binding by selective opioid agonists in the rat brain membrane was performed after naloxonazine pretreatment in vivo. / The specificity of naloxonazine was dependant on the nociceptive test used. In the tail-immersion test, intracranial naloxonazine (1 ug 4 hours before testing) produced a nonparallel right shift of the dose effect relations of all three agonists studied, consistent with long lasting "irreversible" antagonist properties of naloxonazine. In the formalin test, the same naloxonazine pretreatment regimen produced parallel right shift of the morphine dose effect relation but failed to alter the effects of M6G and sufentanil, suggesting either "reversible" antagonist properties or a more complex mechanism. Displacement binding assays suggest that naloxonazine interacts with mu and delta opioid receptor sites. / The data imply that naloxonazine interacts in a long lasting manner with more than one opioid receptor subtype. An allosteric interaction between opioid receptor subtypes is proposed to explain the effects in the formalin test.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59527 |
| Date | January 1990 |
| Creators | Chen, Lei, 1961- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Pharmacology & Therapeutics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001233362, proquestno: AAIMM63660, Theses scanned by UMI/ProQuest. |
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