A Pharmacological Analysis of Levonantradol Antinociception in Mice

Abstract

Using the hot plate test, the potency and mechanism of the analgesic activity of levonantradol was studied in mice. Levonantradol is 10 to 30 times more potent than morphine; the antinociception can be only partially blocked by naloxone. Similar limited antagonism by cholinergics indicates possible opiodergic mechanism. The role of serotoninergic pathways is unclear; antinociception is partially blocked by 5,7‐dihydroxytryptamine, unaffected by p‐chlorophenylalanine, and potentiated by cyproheptadine. Levonantradol blocks naloxone‐induced signs of abstinence in morphine‐dependent mice, being 3000 times more potent than morphine and 300 times more potent than Δ9‐tetrahydrocannabinol (THC).

Inhalation exposure to smoke from synthetic “marijuana” produces potent cannabimimetic effects in mice

“…The second objective of this study was to determine whether inhalation exposure to smoke from Buzz produces cannabimimetic behavioral activity in the tetrad test, a widely used assay to investigate cannabimimetic properties of THC and other cannabinoids, including 1) antinociception, 2) catalepsy, 3) hypothermia, and 4) hypomobility (Martin et al, 1991). Other measures of cannabinoid activity, including hyperreflexia (Long et al, 2009; Patel and Hillard, 2001), straub tail (Cutler and Mackintosh, 1975; Jacob et al, 1981), ptosis (i.e., drooping eyelids; Aceto et al, 1998), and loss of righting reflex were also assessed. The third goal of this project was to examine whether CB 1 receptors mediate the pharmacological effects elicited by Buzz, using the CB 1 receptor antagonist/inverse agonist rimonabant.…”

Effects of fixed-ratio length on the development of tolerance to decreased responding by l-nantradol

“…/-Nantradol is a synthetic cannabinoid with several effects resembling those of morphine. /-Nantradol has potent analgesic effects (Johnson et al 1981 ;Jain et al 1981), it can block morphine-abstinence signs (Lal et al 1981 ;Jacob et al 1981), and it has effects like morphine on spinal reflexes (Gilbert 1981). None of these effects of/-nantradol is antagonized by naloxone or naltrexone, however, (Yaksh 1981;Gilbert 1981), and /-nantradol does not substitute for morphine in drug-discrimination tests (Lal et al 1981 ;Young et al 1981).…”

Central GABA‐ergic systems and analgesia

“…Other types of naloxone-insensitive analgesia, such as that produced by certain kinds of stress [e.g., Lewis et al, 19811, by clonidine [Fielding and Lal, 19811, or by subcutaneous electrical stimulation of medial, radial, and saphenous nerves in man [Walker and Katz, 19811, might also involve GABA-ergic systems. However, it should also be recalled that enkephalin action appears to be relatively resistant to naloxone [Lord et al, 1977;Jacob et al, 1981;Nakatsu et al, 19811. In attempting to explain the ineffectiveness of bicuculline in reversing the analgesic action of THIP [Hill et al, 19811, one might consider that the regional distribution in rat brain of the GABA-receptors that bind [3H]THIP is different from the distribution of those that bind [3H]GABA, and that the pharmacological effects of THIP might be mediated primarily by GABA receptors with lower agonist affinity [Falch and Krogsgaard-Larsen, 19821.…”