Animal experiment:

Mice[1]SR–/– mice receive once daily, intraperitoneal (i.p.) injections of vehicle (20% hydroxypropyl β-cyclodextran) or VU0409551 for 5 days at a volume of 10 mL/kg. For the in vivo pharmacokinetic and dose-finding experiments, WT mice (n=5–6/dose) receive vehicle or VU0409551 (10 and 30 mg/kg). For the SR–/– mice reversal studies, WT mice receive vehicle and SR–/– mice receive either vehicle or VU0409551 (30 mg/kg). All mice are killed 2 h after the last injection on day 5[1].

JNJ-46778212 (VU 0409551) is an mGlu5 positive allosteric modulator with an EC50 of 260 nM.

In oral brain/plasma studies, JNJ-46778212 displays excellent CNS penetration[1]. JNJ-46778212 enhances NMDAR function and rescues long-term potentiation in hippocampal slices obtained from SR–/– mice. The administration of JNJ-46778212 to SR–/– mice reverses their deficits in several neuroplasticity signaling pathways and improves their contextual fear memory[2].

References:
[1]. Conde-Ceide S, et al. Discovery of VU0409551/JNJ-46778212: An mGlu5 Positive Allosteric Modulator Clinical Candidate Targeting Schizophrenia. ACS Med Chem Lett. 2015 May 20;6(6):716-20.