Norbinaltorphimine dihydrochloride

Norbinaltorphimine dihydrochloride is a potent and selective κ opioid receptor antagonist.

Signaling Pathways >> GPCR/G Protein >> Opioid Receptor

Signaling Pathways >> Neuronal Signaling >> Opioid Receptor

Research Areas >> Neurological Disease

κ opioid receptor[1]

Norbinaltorphimine reversibly antagonize the effects of κ agonists with pA2 values of 10.2-10.4. Norbinaltorphimine is much less potent as an antagonist at μ and δ receptors, pA2 values are 7.4-7.6 and 7.6-7.8, respectively[1].

Norbinaltorphimine has weak and inconsistent effects on THC-induced taste avoidance in adolescent rats in that Norbinaltorphimine both attenuates and strengthens taste avoidance dependent on dose and trial. Norbinaltorphimine has limited impact on the final one-bottle avoidance and no effects on the two-bottle preference test. Interestingly, Norbinaltorphimine has no effect on THC-induced taste avoidance in adult rats as well[2]. Norbinaltorphimine pretreatment significantly attenuates stress-induced reinstatement of nicotine-CPP, but has no effect on nicotine-primed reinstatement[3].

Rats[2] Norbinaltorphimine is dissolved in sterile H2O at a concentration of 15 mg/mL and administered subcutaneously (SC) at a dose of 15 mg/kg. Male Sprague Dawley rats are ranked according to average water consumption on all habituation cycles and assigned to one of two groups [Norbinaltorphimine (n=42) and Vehicle (n=42)], such that mean water intake is comparable among groups. On PND 34 (approximately 24 h prior to conditioning, see below), subjects assigned to the Norbinaltorphimine group are injected with Norbinaltorphimine (15 mg/kg) and subjects assigned to the Vehicle group are injected with the Norbinaltorphimine vehicle at an equal volume[2]. Mice[3] Mice are conditioned with 0.5 mg/kg nicotine, injected subcutaneously (s.c.) for 3 days and tested in the nicotine-conditioned place preference (CPP) model. After 3 days extinction, Norbinaltorphimine (10 mg/kg, s.c.) is administered 16 h prior to a priming dose of nicotine (0.1 mg/kg, s.c.), and mice are tested in the CPP model for nicotine-induced reinstatement of CPP. A separate group of mice is subjected to a 2-day modified forced swim test (FST) paradigm to induce stress after 3 days extinction from CPP. Mice are given vehicle or Norbinaltorphimine (10 mg/kg, s.c.) 16 h prior to each FST session[3].

[1]. Birch PJ, et al. Norbinaltorphimine: antagonist profile at kappa opioid receptors. Eur J Pharmacol. 1987 Dec 15;144(3):405-8.

[2]. Flax SM, et al. Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats. Psychopharmacology (Berl). 2015 Sep;232(17):3193-201.

[3]. Jackson KJ, et al. Effects of the kappa opioid receptor antagonist, norbinaltorphimine, on stress and drug-induced reinstatement of nicotine-conditioned place preference in mice. Psychopharmacology (Berl). 2013 Apr;226(4):763-8.