Uses
Naloxone benzoylhydrazone (NalBzoH) is a mixed agonist/antagonist. Naloxone benzoylhydrazone is a prototypic κ3-opioid receptor agonist, and a partial agonist at the cloned μ and δ opioid receptors, and an antagonist at opioid-like NOP receptors. Naloxone benzoylhydrazone has potently analgesia effect[1][2][3].
Biological Activity
Mixed opioid receptor agonist/antagonist. Acts as a potent and full agonist at κ , and a partial agonist at μ and δ opioid receptors (pEC 50 values are 9.45, 8.74 and 8.61 in a cAMP assay, 9.70, 8.59 and 8.49 in a [ 35 S]GTP γ S binding assay respectively). Fails to exert agonist effects at NOP receptors and antagonizes agonist-induced NOP activation. Stimulates κ -, μ - and δ -mediated analgesia and blocks NOP-induced supraspinal nociception.
in vivo
Analgesic studies in mice examining increasing doses of Naloxone benzoylhydrazone with a fixed dose of morphine reveals a biphasic curve. Naloxone benzoylhydrazone at doses as low as 1 μg/kg partially antagonized morphine analgesia. Higher Naloxone benzoylhydrazone doses continued to inhibit morphine analgesia in a dose-dependent manner, with the 1-mg/kg dose antagonizing completely morphine analgesia. As the Naloxone benzoylhydrazone dose increased beyond 1 mg/kg analgesia returned. Naloxone benzoylhydrazone also prduces a similar analgesic response when administered alone in mice and also is active in rats. Naloxone benzoylhydrazone has excellent p.o. activity, with an analgesic potency in mice equivalent to s.c. administration. In addition to blocking morphine analgesia, low doses of Naloxone benzoylhydrazone also partially reverses the inhibition of gastrointestinal transit in mice produced by morphine, antagonizes completely morphine lethality and precipitates withdrawal in morphine-dependent mice[4].
References
[1] Olianas MC, et al. Agonist activity of naloxone benzoylhydrazone at recombinant and native opioid receptors. Br J Pharmacol. 2006 Feb;147(4):360-70. DOI:
10.1038/sj.bjp.0706601[2] Connor M, et al. Has the sun set on kappa3-opioid receptors? Br J Pharmacol. 2006 Feb;147(4):349-50. DOI:
10.1038/sj.bjp.0706603[3] Paul D, et al. Naloxone benzoylhydrazone (NalBzoH) analgesia. J Pharmacol Exp Ther. 1990 Nov;255(2):769-74. PMID:2173757
[4] Gistrak MA, et al. Pharmacological actions of a novel mixed opiate agonist/antagonist: naloxone benzoylhydrazone. J Pharmacol Exp Ther. 1989 Nov;251(2):469-76. PMID:2553921
