Increased Naloxone Potency Induced by Pretreatment With Morphine and Nalbuphine in Mice

Abstract

Both morphine and nalbuphine were effective in suppressing the abdominal constriction response induced by intraperitoneal injection of acetic acid in mice. On a weight to weight basis, nalbuphine was more potent than morphine in this test. However, the effect of nalbuphine was more effectively blocked by naloxone. Pretreatment with morphine 2.0 mg/kg subcutaneously did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later. However, naloxone was about 1.4-fold more effective in antagonizing the antinociceptive effect of both drugs in morphine-pretreated mice than in saline-pretreated animals. Pretreatment with nalbuphine (1.0-2.0 mg/kg s.c.) did not alter the antinociceptive effect of either morphine or nalbuphine measured 3 h later, while naloxone effect was more effective in antagonizing the antinociceptive actions of morphine and nalbuphine. The increases in naloxone potency in antagonizing morphine after nalbuphine pretreatment were not dose-dependent on the amount of nalbuphine in the pretreatment and they were only marginally significant. In addition, these increases were much lower than that induced by morphine pretreatment. On the other hand, the naloxone effectiveness against nalbuphine itself was enhanced to a greater extent than that induced by morphine pretreatment. Furthermore, these increases in naloxone potency showed a dose-dependent relationship to the amount of nalbuphine used in the pretreatment. Based on these results, it was concluded that nalbuphine is an analgesic drug with properties in between those of the full agonist morphine and the partial agonist pentazocine.

Preemptive Intravenous Nalbuphine for the Treatment of Post-Operative Visceral Pain: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

“…Nalbuphine is a noncontrolled, inexpensive, opioid analgesic which has been used clinically for decades. Nalbuphine has been proven to relieve both visceral and somatic pain in mouse analgesiometric studies [15][16][17][18]. Furthermore, it is more potent for visceral pain than somatic pain with an ED50 (0.44 mg kg -1 ) in abdominal constriction response induced by acetic acid in mice [16].…”

“…Nalbuphine has been proven to relieve both visceral and somatic pain in mouse analgesiometric studies [ 15 – 18 ]. Furthermore, it is more potent for visceral pain than somatic pain with an ED50 (0.44 mg kg –1 ) in abdominal constriction response induced by acetic acid in mice [ 16 ]. Nalbuphine agonize the kappa receptor and antagonize the mu receptor.…”

The Anti-Nociceptive Potential of Tulathromycin against Chemically and Thermally Induced Pain in Mice

“…In the 1st main group, the four subgroups were treated with either a small or large dose of tulathromycin (20 or 40 mg/kg BW, subcutaneously (s.c.), respectively) which are around the tulathromycin dose (28 mg/kg of BW) used previously in mice [ 25 , 26 ], or nalbuphine hydrochloride at 2.2 mg/kg BW, s.c. [ 27 , 28 ] as a standard central analgesic or normal saline as a control, and one hour later, the mice were assigned for the hot-plate test. The s.c. injection of tulathromycin to mice at the two tested doses showed no signs of toxicity except for an abnormal small localized soft lump at the injection site and disappeared within 2 h.…”

“…In the 1 st main group, the four subgroups were treated with either a small or large dose of tulathromycin (20 or 40 mg/kg BW, subcutaneously (s.c.), respectively) which are around the tulathromycin dose (28 mg/kg of BW) used previously in mice [25,26], or nalbuphine hydrochloride at 2.2 mg/kg BW, s.c. [27,28] as a standard central analgesic or…”

Strategies for DevelopingκOpioid Receptor Agonists for the Treatment of Pain with Fewer Side Effects

“…The mixed KOPr agonist and partial MOPr antagonist, nalbuphine, has potent antinociceptive effects in male (Pick et al, 1992;Patrick et al, 1999;Ortiz et al, 2007) and female mice (Wong and Wai, 1984), rabbits (Yoa-Pu et al, 1998) and humans (Kshirsagar et al, 2008) in a wide range of pain models (Table 2). Moreover, nalbuphine attenuates cocaine abuse-related effects in men (Mello et al, 2005) with lower respiratory depression and fewer psychomimetic side-effects compared to other narcotic analgesics such as nalorphine or pentazocine (Schmidt et al, 1985).…”