nor-Binaltorphimine (nor-BNI) is a potent and highly selective κ-opioid receptor antagonist. The compound was created at the University of Minnesota in the Portoghese laboratory and has remained the reference κ-antagonist in opioid pharmacology for decades (Tocris). We supply it as the dihydrochloride — the salt form is water-soluble, unlike the free base.
Selectivity is the main value. nor-BNI acts at the κ receptor with no effect on µ- or δ-opioid receptors (Sigma-Aldrich). It is precisely this clean profile that made it the tool used in hundreds of studies to separate the κ component from the rest of the opioid system. The molecule is a dimer: two naltrexone-like halves joined by a pyrrole bridge, and it is this architecture that confers the selectivity.
The structural basis of selectivity. SAR work showed that potent antagonism and selectivity arise only when the molecule contains a basic N17' nitrogen. This points to an interaction with extracellular domains of the κ receptor rich in acidic amino acid residues — the so-called address subsite that distinguishes the κ receptor from its relatives (J Med Chem, 1994).
Exceptionally long-lasting action. This is nor-BNI's best-known property: a single administration blocks κ receptors for weeks. Pharmacokinetic work showed that the reason is not slow plasma clearance but the nature of the receptor interaction itself (Neurosci Lett, 2013). In practice this means one injection covers an entire experimental protocol without repeat dosing.
Fields of application. The compound is widely used in research on pain, addiction, anxiety, depression and sleep (Sigma-Aldrich). The κ-opioid system attracts attention as a target for non-addictive analgesia, and nor-BNI is the standard tool for verifying whether an effect is genuinely κ-mediated.
Withdrawal and neurochemistry. In butorphanol-dependent rats, nor-BNI precipitated withdrawal and excitatory amino acid release in the locus coeruleus — and, tellingly, did not do so in morphine-dependent animals (J Pharmacol Exp Ther, 1997). This contrast directly demonstrates that the κ and µ components of dependence separate pharmacologically.
Receptor regulation. nor-BNI was used to dissect the differential agonist regulation of the human κ-opioid receptor — work that established the understanding of desensitisation and internalisation in this system (J Neurochem, 1997).
Solubility. The salt dissolves in water to 50 mM (Abcam), roughly 37 mg/mL — for a complex alkaloid dimer this is a substantial practical advantage over the free base.
Supplied as a solid powder, purity ≥98% (HPLC), CAS 113158-34-2.
For research use only. This product is not a medicine, food supplement or cosmetic. Not intended for human or animal use. Sold to persons aged 18+.
