Ro 64-6198 is a nonpeptide, high-affinity, and brain penetration N/OFQ receptor (NOP) agonist (EC50: 25.6 nM). Ro 64-6198 is at least 100 times more selective for the NOP receptor over the classic opioid receptors.

Ro 64-6198 does recruit both arrestin3 (EC50 of 0.912 μM) and arrestin2 (EC50: 1.20 μM) to the NOP receptor in a concentration-dependent manner comparably with N/OFQ. Ro 64-6198 also produces rapid desensitization of the NOP receptor. Ro 64-6198 causes functional desensitization of the receptor, a loss in binding sites, and an apparent decrease in binding affinity. The desensitization produced by Ro 64-6198 is not reversed by acidic washes [1][2].

Ro 64-6198 is anxiolytic in several neophobic tests at low doses, including the marble burying test in mice, the elevated plus-maze in rats, and the open field test in rats. In the marble burying test, Ro 64-6198 (1 mg/kg, i.p.,) produces a decrease in the number of marbles buried, without altering locomotor activity, indicating a decrease in neophobia and anxiety. Ro 64-6198 (0.32-3 mg/kg, i.p.,) selectively increases the number of open arm transitions and time spent in the open arms of the elevated plus-maze without affecting closed-arm transitions or locomotor activity in the closed arms. Ro 64-6198 (0.32-3 mg/kg) attenuates the inhibition of exploration that results from the stress of a novel environment [1].