Nociceptin/orphanin FQ (N/OFQ) is a neuropeptide that selectively interacts with the NOP receptor. NOP receptor is a member of the opioid receptor family. The N/OFQ-NOP system modulates several biological functions. It includes pain transmission, stress and anxiety, learning and memory, locomotor activity, food intake, and the motivational properties of drugs of abuse. N/OFQ modulates several biological functions by activating a specific G-protein coupled receptor (NOP). Few molecules are available that selectively activate or block the NOP receptor. UFP-101 is a potent and selective antagonist of the NOP receptor. It binds to the human recombinant NOP receptor expressed in (CHO cells with high affinity (pK_i 10.2). UFP-101 also shows more than 3000 fold selectivity over classical opioid receptors. Moreover, it competitively antagonizes the effects of N/OFQ on GTPγ³⁵S binding in CHO_hNOP cell membranes and on cyclic AMP accumulation in CHO_hNOP cells.

UFP-101 acts as a pure, competitive, and selective antagonist at the NOP receptor.

UFP-101 displays >3000-fold selectivity over δ, μ and κ opioid receptors. It also shows an antidepressant-like effect. Moreover, UFP-101 does not produce per se any significant inhibition of forskolin-stimulated cyclic AMP formation. In addition, UFP-101 is also active in vivo in the mouse. It antagonizes the effects of N/OFQ in the tail withdrawal and locomotor activity assays. Furthermore, it competes with [³H]-N/OFQ for binding to the recombinant NOP receptor yielding an affinity similar to that of the natural peptide.

UFP-101 is one of the most potent antagonists and, clearly, the most selective for NOP receptors. Thus, it is a useful pharmacological tool for the investigation of the central and peripheral biological functions regulated by the N/OFQ-NOP receptor system. It also used for defining the therapeutic potential of NOP receptor ligands.

Reference:

Calo G, et al. Br J Pharmacol. 2002;136(2):303-311.