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Ro 65-6570 is a nonpeptidic, high-affinity (Ki = 0.52 against 0.1 nM OFQ for binding human ORL1) nociceptin/orphanin FQ (N/OFQ) receptor ORL-1 (KOR-3, NOP) agonist (EC50 = 40 nM by GTPγS binding assay; IC50 = 0.28 nM against 1 μM forskolin-stimulated cellular cAMP accumulation) with good selectivity over opioid receptors μ, k, δ (Ki = 5.9, 26, 250 nM against 1.5 nM naloxone, 3 nM naloxone, 0.3 nM [Ile5,6]-deltorphin II for binding respective receptors), dopamine and serotonin receptors (Ki = 520 nM/D2, 1210 nM/D3,350 nM/D4.4; Ki ≥1 μM for 5HT 1Dα, 2A, 2C, 6, 7). Ro 65-6570 elicits ORL1-dependent anxiolytic-like effects in rats in vivo (0.32-3.2 mg/kg i.p.; elevated plus maze) without affecting spontaneous locomotion. Unlike OFQ, Ro 65-6570 does not affect cocaine-induced conditioned place preference (CPP) in rats.
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