Naloxone benzoylhydrazone (NalBzoH) analgesia Journal Article
| Authors: | Paul, D.; Levison, J. A.; Howard, D. H.; Pick, C. G.; Hahn, E. F.; Pasternak, G. W. |
| Article Title: | Naloxone benzoylhydrazone (NalBzoH) analgesia |
| Abstract: | Naloxone benzoylhydrazone (NalBzoH) is a novel mixed agonist/antagonist. Against μ agonists, NAlBzoH is a potent antagonist with a prolonged duration of action corresponding to its extremely slow rate of dissociation from μ receptors in binding assays. In the present studies, NalBzoH also antagonized μ analgesia, reversing both μ1 and μ2 analgesia independently elicited by intracerebroventricular or intrathecal [D-Ala2,MePhe4,Gly(ol)5]enkephalin injections. It also antagonized κ1 analgesia elicited by U50,488H and δ analgesia produced by intrathecal [D-Pen2,D-Pen5]enkephalin. Yet, at higher doses, NalBzoH alone produced analgesia in the tail-flick, hot plate and writhing assays. Neither the μ-selective antagonist β-funaltrexamine, the δ-selective antagonist naltrindole, nor the κ1-selective antagonist norbinaltorphimine reversed NalBzoH analgesia in the tail-flick test. Analgesia observed with systemically administered NalBzoH ws reversed easily by the antagonist WIN44,441 when it was given intracerebroventricularly, but not intrathecally. These observations confirm the opioid nature of NalBzoH analgesia and imply a supraspinal mechanism of action. In contrast, intrathecal, but not intracerebroventricular WIN44,441 reversed analgesia from systemic U50,488H quite potently. Thus, NalBzoH antagonizes μ, δ and κ1 actions while retaining its ability to elicit analgesia through a novel and distinct supraspinal κ3 system. |
| Keywords: | controlled study; nonhuman; mouse; animal; mice; animal experiment; morphine; analgesics; analgesia; mu opiate receptor; receptors, opioid, mu; tail flick test; naloxone; opiate receptor; beta funaltrexamine; enkephalin[2,5 dextro penicillamine]; naltrindole; hot plate test; delta opiate receptor; receptor subtype; receptors, opioid, delta; 3,4 dichloro n methyl n [2 (1 pyrrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate; naloxone benzoylhydrazone; kappa opiate receptor; enkephalin[2 dextro alanine 4 methylphenylalanine 5 glycine]; narcotic antagonists; subcutaneous drug administration; receptors, opioid; intracerebroventricular drug administration; norbinaltorphimine; male; priority journal; article; receptors, opioid, kappa; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin, d-penicillamine (2,5)-; intrathecal drug administration; quadazocine; writhing test; azocines |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 255 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 1990-11-01 |
| Start Page: | 769 |
| End Page: | 774 |
| Language: | English |
| PUBMED: | 2173757 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 27 January 2020 -- Source: Scopus |
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