Comparison of naloxonazine and β-funaltrexamine antagonism of μ1 and μ2 opioid actions

Chaim G. Pick*, Dennis Paul, Gavril W. Pasternak

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

β-Funaltrexamine (β-FNA) irreversibly blocks morphine analgesia, lethality and its inhibition of gastrointestinal transit, confirming that these actions involve μ receptors. In dose-response studies, β-FNA antagonized all the actions with similar potencies (ID50 values of 12.1, 11.3 and 12.3 mg/kg, respectively). β-FNA also reduced intra-cerebroventricular and intrathecal DAMGO analgesia equally well (ID50 values of 6.09 and 7.7 mg/kg, respectively). Naloxonazine blocked systemic morphine analgesia (ID50 value 9.5 mg/kg) and supraspinal DAMGO analgesia (ID50 value 6.1 mg/kg) as potently as β-FNA. However, against spinal DAMGO analgesia, morphine's inhibition of gastro-intestinal transit or lethality, naloxonazine (ID50 values 38.8, 40.7 and 40.9 mg/kg, respectively) was significantly less active than β-FNA (p < 0.05). β-FNA remains a valuable tool in the classification of μ opioid actions. Within the μ category, actions can be defined as either μ1 (naloxonazine-sensitive) or μ2 (naloxonazine-insensitive).

Original languageEnglish
Pages (from-to)2005-2011
Number of pages7
JournalLife Sciences
Volume48
Issue number21
DOIs
StatePublished - 1991
Externally publishedYes

Funding

FundersFunder number
National Institutes of Health
National Institute on Drug Abuse
American Cancer SocietyPDT169
National Cancer InstituteP01CA008748, K02DA000138

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