Effects of 14-methoxymetopon, a potent opioid agonist, on the responses to the tail electric stimulation test and plus-maze activity in male rats: neuroendocrine correlates

14-methoxymetopon, a highly potent μ opioid agonist, biphasically affects ethanol intake in Sardinian alcohol-preferring rats

“…However, the systemic doses of 14-MM (12.25, 30 μg/kg) needed to stimulate drinking in sP rats were approximately two orders lower than those needed for morphine (1.0-2.5 mg/kg) in previous studies, including those performed in sP rats (Vacca et al 2002). This apparently greater potency of 14-MM is consistent with its comparably greater antinociceptive potency than morphine (King et al 2003;Uriguen et al 2002) and may be partly explained by the greater binding affinity of 14-MM than morphine for μ opioid receptors in radioligand binding assays Zernig et al 2000;Mahurter et al 2006). Naltrexone, a relatively subtype nonselective opioid antagonist, completely blocked the facilitatory effect of systemic 14-MM on ethanol intake, confirming an opioid-mediated action of this derivative of the 14-alkoxymorphinan series of opioids.…”

“…study. These vehicles were chosen to allow a more direct comparison with previously reported potencies and durations of action of the compound in other in vivo assays (Schmidhammer et al 1990;Uriguen et al 2002;Schutz et al 2003;Linseman and Harding 1990;Wild and Reid 1990), given the known effects of vehicles on bioactivity (e.g., Ozawa et al 1998). Naltrexone hydrochloride, or 17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride (Sigma Aldrich, St. Louis, MO, USA), was dissolved in bacteriostatic isotonic saline.…”

“…Functionally, 14-MM is an extremely potent analgesic in multiple tests of antinociception in rats, mice, and dogs (Furst et al 1993;King et al 2003;Schmidhammer et al 1990;Uriguen et al 2002). Given systemically, 14-MM is 100-20,000-fold more potent than morphine in producing analgesia (Furst et al 1993), and up to one million-fold more potent than morphine following supraspinal or spinal central administration (King et al 2003).…”

Synthesis and Biological Evaluation of 14-Alkoxymorphinans. 22. Influence of the 14-Alkoxy Group and the Substitution in Position 5 in 14-Alkoxymorphinan-6-ones on in Vitro and in Vivo Activities

“…Furthermore, we investigated the influence of selected substitutents in position 14 on in vitro agonist activity, antinociceptive potency and inhibition of gastrointestinal motility. We have synthesized N-methylmorphinan-6-ones substituted in position 14 with allyloxy (6), benzyloxy (7,8), 1-naphthylmethoxy (9), and 2,6-dichlorobenzyloxy (10) (Figure 1). In addition, the 14-ethoxy-substituted N-(2-phenlyethyl)morphinan-6-one 11 was prepared to investigate the influence of a N-phenylethyl group in this class of compounds.…”

Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear-potentiated startle: tolerance, cross-tolerance, and blockade by naloxone

“…Using animal models of unconditioned and conditioned fear, several studies have described anxiolytic-like effects of opioids. Morphine (Motta and Brandao 1993;Koks et al 1999;Anseloni et al 1999;Sasaki et al 2002;Uriguen et al 2002;Shin et al 2003), as well as selective agonists for the μ-opioid receptor (Asakawa et al 1998;Uriguen et al …”